Motif 895 (n=4,045)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A087WZ62 | None | S246 | ochoa | Mannosyltransferase (EC 2.4.1.-) | None |
| A0A0A0MRY4 | None | S184 | ochoa | Spermatogenesis-associated protein 13 | None |
| A0A0J9YX86 | GOLGA8Q | S41 | ochoa | Golgin A8 family member Q | None |
| A0MZ66 | SHTN1 | S464 | ochoa | Shootin-1 (Shootin1) | Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth. Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth. In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons. {ECO:0000250|UniProtKB:A0MZ67, ECO:0000250|UniProtKB:Q8K2Q9}. |
| A2RUB1 | MEIOC | S130 | ochoa | Meiosis-specific coiled-coil domain-containing protein MEIOC (Meiosis-specific with coiled-coil domain protein) | Is required for meiosis completion in both male and female germ cells. Confers stability to numerous meiotic mRNAs in gonads allowing proper initiation and progression into meiosis prophase I. The function may involve YTHDC2 and is independent of induction by retinoic acid (RA). Maintains an extended meiotic prophase I by properly promoting the transition from a mitotic to a meiotic cell cycle program by binding transcripts through its interaction with YTHDC2 that regulate the mitotic cell cycle. {ECO:0000250|UniProtKB:A2AG06}. |
| A2RUS2 | DENND3 | S502 | ochoa | DENN domain-containing protein 3 | Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity). {ECO:0000250|UniProtKB:A2RT67, ECO:0000269|PubMed:20937701}. |
| A4D1P6 | WDR91 | S326 | ochoa | WD repeat-containing protein 91 | Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May play a role in meiosis (By similarity). {ECO:0000250|UniProtKB:Q7TMQ7, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989}. |
| A5A3E0 | POTEF | S932 | ochoa | POTE ankyrin domain family member F (ANKRD26-like family C member 1B) (Chimeric POTE-actin protein) | None |
| A5YKK6 | CNOT1 | S1703 | ochoa | CCR4-NOT transcription complex subunit 1 (CCR4-associated factor 1) (Negative regulator of transcription subunit 1 homolog) (NOT1H) (hNOT1) | Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity. Plays a role in rapid sperm motility via mediating timely mRNA turnover (By similarity). {ECO:0000250|UniProtKB:Q6ZQ08, ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:32354837}. |
| A6NDB9 | PALM3 | S260 | ochoa | Paralemmin-3 | ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling. {ECO:0000269|PubMed:21187075}. |
| A6NDB9 | PALM3 | S548 | ochoa | Paralemmin-3 | ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling. {ECO:0000269|PubMed:21187075}. |
| A6NED2 | RCCD1 | S268 | ochoa | RCC1 domain-containing protein 1 | Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with KDM8 (PubMed:24981860). Possibly together with KDM8, is involved in proper mitotic spindle organization and chromosome segregation (PubMed:24981860). Plays a role in regulating alpha-tubulin deacetylation and cytoskeletal microtubule stability, thereby promoting cell migration and TGF-beta-induced epithelial to mesenchymal transition (EMT), potentially through the inhibition of KDM8 (PubMed:28455245). {ECO:0000269|PubMed:24981860, ECO:0000269|PubMed:28455245}. |
| A6NKF1 | SAC3D1 | S210 | ochoa | SAC3 domain-containing protein 1 (SAC3 homology domain-containing protein 1) | Involved in centrosome duplication and mitotic progression. {ECO:0000250}. |
| A6NKT7 | RGPD3 | S381 | ochoa | RanBP2-like and GRIP domain-containing protein 3 | None |
| A6NMY6 | ANXA2P2 | S26 | ochoa | Putative annexin A2-like protein (Annexin A2 pseudogene 2) (Lipocortin II pseudogene) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. {ECO:0000250}. |
| A6NMZ7 | COL6A6 | S819 | ochoa | Collagen alpha-6(VI) chain | Collagen VI acts as a cell-binding protein. {ECO:0000250}. |
| A8CG34 | POM121C | S348 | ochoa | Nuclear envelope pore membrane protein POM 121C (Nuclear pore membrane protein 121-2) (POM121-2) (Pore membrane protein of 121 kDa C) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| B0FP48 | UPK3BL1 | S245 | ochoa | Uroplakin-3b-like protein 1 | None |
| B0I1T2 | MYO1G | S325 | ochoa | Unconventional myosin-Ig [Cleaved into: Minor histocompatibility antigen HA-2 (mHag HA-2)] | Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration. Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication. Also required in B-cells, where it regulates different membrane/cytoskeleton-dependent processes. Involved in Fc-gamma receptor (Fc-gamma-R) phagocytosis. {ECO:0000250|UniProtKB:Q5SUA5}.; FUNCTION: [Minor histocompatibility antigen HA-2]: Constitutes the minor histocompatibility antigen HA-2. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and their expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. HA-2 is restricted to MHC class I HLA-A*0201. {ECO:0000269|PubMed:11544309, ECO:0000305}. |
| B0I1T2 | MYO1G | S851 | ochoa | Unconventional myosin-Ig [Cleaved into: Minor histocompatibility antigen HA-2 (mHag HA-2)] | Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration. Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication. Also required in B-cells, where it regulates different membrane/cytoskeleton-dependent processes. Involved in Fc-gamma receptor (Fc-gamma-R) phagocytosis. {ECO:0000250|UniProtKB:Q5SUA5}.; FUNCTION: [Minor histocompatibility antigen HA-2]: Constitutes the minor histocompatibility antigen HA-2. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and their expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. HA-2 is restricted to MHC class I HLA-A*0201. {ECO:0000269|PubMed:11544309, ECO:0000305}. |
| D6RIA3 | C4orf54 | S889 | ochoa | Uncharacterized protein C4orf54 (Familial obliterative portal venopathy) | None |
| F5H4A9 | C3orf80 | S153 | ochoa | Uncharacterized membrane protein C3orf80 | None |
| I6L899 | GOLGA8R | S41 | ochoa | Golgin subfamily A member 8R | None |
| O00148 | DDX39A | S37 | ochoa | ATP-dependent RNA helicase DDX39A (EC 3.6.4.13) (DEAD box protein 39) (Nuclear RNA helicase URH49) | Helicase that plays an essential role in mRNA export and is involved in multiple steps in RNA metabolism including alternative splicing (PubMed:33941617, PubMed:38801080). Regulates nuclear mRNA export to the cytoplasm through association with ECD (PubMed:33941617). Also involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export by stimulating the RNA binding of adapter PHAX (PubMed:39011894). Plays a role in the negative regulation of type I IFN production by increasing the nuclear retention of antiviral transcripts and thus reducing their protein expression (PubMed:32393512). Independently of the interferon pathway, plays an antiviral role against alphaviruses by binding to a 5' conserved sequence element in the viral genomic RNA (PubMed:37949067). {ECO:0000269|PubMed:15047853, ECO:0000269|PubMed:17548965, ECO:0000269|PubMed:32393512, ECO:0000269|PubMed:33941617, ECO:0000269|PubMed:37949067, ECO:0000269|PubMed:38801080}. |
| O00151 | PDLIM1 | S118 | ochoa | PDZ and LIM domain protein 1 (C-terminal LIM domain protein 1) (Elfin) (LIM domain protein CLP-36) | Cytoskeletal protein that may act as an adapter that brings other proteins (like kinases) to the cytoskeleton (PubMed:10861853). Involved in assembly, disassembly and directioning of stress fibers in fibroblasts. Required for the localization of ACTN1 and PALLD to stress fibers. Required for cell migration and in maintaining cell polarity of fibroblasts (By similarity). {ECO:0000250|UniProtKB:P52944, ECO:0000269|PubMed:10861853}. |
| O00159 | MYO1C | S1041 | ochoa | Unconventional myosin-Ic (Myosin I beta) (MMI-beta) (MMIb) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: [Isoform 3]: Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation. {ECO:0000250|UniProtKB:Q9WTI7}. |
| O00161 | SNAP23 | S161 | ochoa|psp | Synaptosomal-associated protein 23 (SNAP-23) (Vesicle-membrane fusion protein SNAP-23) | Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion. |
| O00186 | STXBP3 | S508 | ochoa | Syntaxin-binding protein 3 (Platelet Sec1 protein) (PSP) (Protein unc-18 homolog 3) (Unc18-3) (Protein unc-18 homolog C) (Unc-18C) | Together with STX4 and VAMP2, may play a role in insulin-dependent movement of GLUT4 and in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes. {ECO:0000250}. |
| O00192 | ARVCF | S602 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00192 | ARVCF | S887 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00255 | MEN1 | S394 | psp | Menin | Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair. {ECO:0000250|UniProtKB:O88559, ECO:0000269|PubMed:11274402, ECO:0000269|PubMed:11526476, ECO:0000269|PubMed:12837246, ECO:0000269|PubMed:12874027, ECO:0000269|PubMed:14992727, ECO:0000269|PubMed:22327296}. |
| O00267 | SUPT5H | S755 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00267 | SUPT5H | S804 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00311 | CDC7 | S277 | ochoa|psp | Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) | Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}. |
| O00311 | CDC7 | S318 | psp | Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) | Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}. |
| O00429 | DNM1L | S693 | psp | Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1) | Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:19411255, PubMed:19638400, PubMed:23283981, PubMed:23530241, PubMed:23921378, PubMed:26992161, PubMed:27145208, PubMed:27145933, PubMed:27301544, PubMed:27328748, PubMed:29478834, PubMed:32439975, PubMed:32484300, PubMed:9570752, PubMed:9786947). Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism (PubMed:23530241, PubMed:23584531, PubMed:33850055). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:23921378, PubMed:29899447). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:29899447). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity). Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:26992161, PubMed:27145208, PubMed:27301544, PubMed:27328748). Facilitates developmentally regulated apoptosis during neural tube formation (By similarity). Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues (By similarity). Required for formation of endocytic vesicles (PubMed:20688057, PubMed:23792689, PubMed:9570752). Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (PubMed:17015472, PubMed:23792689). Required for programmed necrosis execution (PubMed:22265414). Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834). {ECO:0000250|UniProtKB:Q8K1M6, ECO:0000269|PubMed:11514614, ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:17015472, ECO:0000269|PubMed:17301055, ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:17553808, ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19342591, ECO:0000269|PubMed:19411255, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:20688057, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531, ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:29899447, ECO:0000269|PubMed:32439975, ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9786947}.; FUNCTION: [Isoform 1]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}.; FUNCTION: [Isoform 4]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}. |
| O00444 | PLK4 | S22 | psp | Serine/threonine-protein kinase PLK4 (EC 2.7.11.21) (Polo-like kinase 4) (PLK-4) (Serine/threonine-protein kinase 18) (Serine/threonine-protein kinase Sak) | Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:30804208}. |
| O00444 | PLK4 | S305 | psp | Serine/threonine-protein kinase PLK4 (EC 2.7.11.21) (Polo-like kinase 4) (PLK-4) (Serine/threonine-protein kinase 18) (Serine/threonine-protein kinase Sak) | Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:30804208}. |
| O00533 | CHL1 | S1147 | ochoa | Neural cell adhesion molecule L1-like protein (Close homolog of L1) [Cleaved into: Processed neural cell adhesion molecule L1-like protein] | Extracellular matrix and cell adhesion protein that plays a role in nervous system development and in synaptic plasticity. Both soluble and membranous forms promote neurite outgrowth of cerebellar and hippocampal neurons and suppress neuronal cell death. Plays a role in neuronal positioning of pyramidal neurons and in regulation of both the number of interneurons and the efficacy of GABAergic synapses. May play a role in regulating cell migration in nerve regeneration and cortical development. Potentiates integrin-dependent cell migration towards extracellular matrix proteins. Recruits ANK3 to the plasma membrane (By similarity). {ECO:0000250}. |
| O00622 | CCN1 | S205 | ochoa | CCN family member 1 (Cellular communication network factor 1) (Cysteine-rich angiogenic inducer 61) (Insulin-like growth factor-binding protein 10) (IBP-10) (IGF-binding protein 10) (IGFBP-10) (Protein CYR61) (Protein GIG1) | Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CCN1-mediated gene regulation is dependent on heparin-binding. Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1. Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-v/beta-5 and cell proliferation through integrin alpha-v/beta-3. {ECO:0000269|PubMed:11584015}. |
| O00750 | PIK3C2B | S95 | ochoa | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (PI3K-C2-beta) (PtdIns-3-kinase C2 subunit beta) (EC 2.7.1.137) (EC 2.7.1.154) (C2-PI3K) (Phosphoinositide 3-kinase-C2-beta) | Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns (PubMed:10805725, PubMed:11533253, PubMed:9830063). Does not phosphorylate PtdIns(4,5)P2 (PubMed:9830063). May be involved in EGF and PDGF signaling cascades (PubMed:10805725). {ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11533253, ECO:0000269|PubMed:9830063}. |
| O00750 | PIK3C2B | S225 | ochoa | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (PI3K-C2-beta) (PtdIns-3-kinase C2 subunit beta) (EC 2.7.1.137) (EC 2.7.1.154) (C2-PI3K) (Phosphoinositide 3-kinase-C2-beta) | Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns (PubMed:10805725, PubMed:11533253, PubMed:9830063). Does not phosphorylate PtdIns(4,5)P2 (PubMed:9830063). May be involved in EGF and PDGF signaling cascades (PubMed:10805725). {ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11533253, ECO:0000269|PubMed:9830063}. |
| O14490 | DLGAP1 | S419 | ochoa | Disks large-associated protein 1 (DAP-1) (Guanylate kinase-associated protein) (hGKAP) (PSD-95/SAP90-binding protein 1) (SAP90/PSD-95-associated protein 1) (SAPAP1) | Part of the postsynaptic scaffold in neuronal cells. |
| O14519 | CDK2AP1 | S84 | ochoa | Cyclin-dependent kinase 2-associated protein 1 (CDK2-associated protein 1) (Deleted in oral cancer 1) (DOC-1) (Putative oral cancer suppressor) | Inhibitor of cyclin-dependent kinase CDK2 (By similarity). Also acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:20523938, PubMed:28977666). {ECO:0000250|UniProtKB:O35207, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:20523938, ECO:0000269|PubMed:28977666}. |
| O14578 | CIT | S795 | ochoa | Citron Rho-interacting kinase (CRIK) (EC 2.7.11.1) (Serine/threonine-protein kinase 21) | Plays a role in cytokinesis. Required for KIF14 localization to the central spindle and midbody. Putative RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 with a tighter specificity in vivo. Displays serine/threonine protein kinase activity. Plays an important role in the regulation of cytokinesis and the development of the central nervous system. Phosphorylates MYL9/MLC2. {ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:27453578}. |
| O14646 | CHD1 | S1328 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O14646 | CHD1 | S1622 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O14647 | CHD2 | S1586 | ochoa | Chromodomain-helicase-DNA-binding protein 2 (CHD-2) (EC 3.6.4.-) (ATP-dependent helicase CHD2) | ATP-dependent chromatin-remodeling factor that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression (By similarity). {ECO:0000250}. |
| O14686 | KMT2D | S1270 | ochoa | Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}. |
| O14686 | KMT2D | S3207 | ochoa | Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}. |
| O14686 | KMT2D | S3468 | ochoa | Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}. |
| O14745 | NHERF1 | S46 | ochoa|psp | Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (NHERF-1) (Ezrin-radixin-moesin-binding phosphoprotein 50) (EBP50) (Regulatory cofactor of Na(+)/H(+) exchanger) (Sodium-hydrogen exchanger regulatory factor 1) (Solute carrier family 9 isoform A3 regulatory factor 1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}. |
| O14818 | PSMA7 | S30 | ochoa | Proteasome subunit alpha type-7 (Proteasome subunit RC6-1) (Proteasome subunit XAPC7) (Proteasome subunit alpha-4) (alpha-4) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response. {ECO:0000269|PubMed:11389899, ECO:0000269|PubMed:11713272, ECO:0000269|PubMed:12119296, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:19442227, ECO:0000269|PubMed:19734229, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| O14818 | PSMA7 | S201 | ochoa | Proteasome subunit alpha type-7 (Proteasome subunit RC6-1) (Proteasome subunit XAPC7) (Proteasome subunit alpha-4) (alpha-4) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response. {ECO:0000269|PubMed:11389899, ECO:0000269|PubMed:11713272, ECO:0000269|PubMed:12119296, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:19442227, ECO:0000269|PubMed:19734229, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| O14867 | BACH1 | S380 | ochoa | Transcription regulator protein BACH1 (BTB and CNC homolog 1) (HA2303) | Transcriptional regulator that acts as a repressor or activator, depending on the context. Binds to NF-E2 DNA binding sites. Plays important roles in coordinating transcription activation and repression by MAFK (By similarity). Together with MAF, represses the transcription of genes under the control of the NFE2L2 oxidative stress pathway (PubMed:24035498). {ECO:0000250|UniProtKB:P97302, ECO:0000269|PubMed:24035498, ECO:0000269|PubMed:39504958}. |
| O14939 | PLD2 | S79 | ochoa | Phospholipase D2 (PLD 2) (hPLD2) (EC 3.1.4.4) (Choline phosphatase 2) (PLD1C) (Phosphatidylcholine-hydrolyzing phospholipase D2) | Function as phospholipase selective for phosphatidylcholine (PubMed:9582313). May have a role in signal-induced cytoskeletal regulation and/or endocytosis (By similarity). {ECO:0000250|UniProtKB:P97813, ECO:0000269|PubMed:9582313}. |
| O14974 | PPP1R12A | S20 | psp | Protein phosphatase 1 regulatory subunit 12A (Myosin phosphatase-targeting subunit 1) (Myosin phosphatase target subunit 1) (Protein phosphatase myosin-binding subunit) | Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity. {ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:20354225}. |
| O14976 | GAK | S760 | ochoa | Cyclin-G-associated kinase (EC 2.7.11.1) (DnaJ homolog subfamily C member 26) | Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1 (PubMed:10625686). May play a role in clathrin-mediated endocytosis and intracellular trafficking, and in the dynamics of clathrin assembly/disassembly (PubMed:18489706). {ECO:0000269|PubMed:10625686, ECO:0000269|PubMed:18489706}. |
| O14983 | ATP2A1 | S610 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) (SR Ca(2+)-ATPase 1) (EC 7.2.2.10) (Calcium pump 1) (Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) | Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677). {ECO:0000250|UniProtKB:P04191, ECO:0000269|PubMed:10914677}. |
| O15014 | ZNF609 | S609 | ochoa | Zinc finger protein 609 | Transcription factor, which activates RAG1, and possibly RAG2, transcription. Through the regulation of RAG1/2 expression, may regulate thymocyte maturation. Along with NIPBL and the multiprotein complex Integrator, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others. {ECO:0000250|UniProtKB:Q8BZ47}.; FUNCTION: [Isoform 2]: Involved in the regulation of myoblast proliferation during myogenesis. {ECO:0000269|PubMed:28344082}. |
| O15027 | SEC16A | S1398 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15027 | SEC16A | S1810 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15042 | U2SURP | S747 | ochoa | U2 snRNP-associated SURP motif-containing protein (140 kDa Ser/Arg-rich domain protein) (U2-associated protein SR140) | None |
| O15055 | PER2 | S662 | psp | Period circadian protein homolog 2 (hPER2) (Circadian clock protein PERIOD 2) | Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndrome and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors. PER appears to regulate circadian control of transcription by at least three different modes. First, interacts directly with the CLOCK-BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription. Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1. The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases. Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-BMAL1 interactions. Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. May propagate clock information to metabolic pathways via the interaction with nuclear receptors. Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like BMAL1 or G6PC1. Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby inhibiting transcriptional activation. Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels. Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas. Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression. May also be involved in the regulation of inflammatory processes. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1. {ECO:0000250|UniProtKB:O54943}. |
| O15061 | SYNM | S1304 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15061 | SYNM | S1432 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15085 | ARHGEF11 | S1505 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15195 | VILL | S762 | ochoa | Villin-like protein | Possible tumor suppressor. |
| O15381 | NVL | S159 | ochoa | Nuclear valosin-containing protein-like (NVLp) (Nuclear VCP-like protein) | Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT (PubMed:22226966). Involved in both early and late stages of the pre-rRNA processing pathways (PubMed:26166824). Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus (PubMed:15469983, PubMed:16782053, PubMed:26456651, PubMed:29107693). Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity (PubMed:26456651, PubMed:28416111, PubMed:29107693). {ECO:0000269|PubMed:15469983, ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26166824, ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:28416111, ECO:0000269|PubMed:29107693}. |
| O15397 | IPO8 | S439 | ochoa | Importin-8 (Imp8) (Ran-binding protein 8) (RanBP8) | Involved in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, may serve as receptor for nuclear localization signals (NLS) and promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:9214382). In vitro mediates the nuclear import of the signal recognition particle protein SRP19 (PubMed:11682607). May also be involved in cytoplasm-to-nucleus shuttling of a broad spectrum of other cargos, including Argonaute-microRNAs complexes, the JUN protein, RELA/NF-kappa-B p65 subunit, the translation initiation factor EIF4E and a set of receptor-activated mothers against decapentaplegic homolog (SMAD) transcription factors that play a critical role downstream of the large family of transforming growth factor beta and bone morphogenetic protein (BMP) cytokines (Probable). {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9214382, ECO:0000305|PubMed:34010604}. |
| O15417 | TNRC18 | S1579 | ochoa | Trinucleotide repeat-containing gene 18 protein (Long CAG trinucleotide repeat-containing gene 79 protein) | None |
| O43166 | SIPA1L1 | S255 | ochoa | Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (High-risk human papilloma viruses E6 oncoproteins targeted protein 1) (E6-targeted protein 1) | Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}. |
| O43166 | SIPA1L1 | S1197 | ochoa | Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (High-risk human papilloma viruses E6 oncoproteins targeted protein 1) (E6-targeted protein 1) | Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}. |
| O43166 | SIPA1L1 | S1639 | ochoa | Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (High-risk human papilloma viruses E6 oncoproteins targeted protein 1) (E6-targeted protein 1) | Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}. |
| O43167 | ZBTB24 | S151 | ochoa | Zinc finger and BTB domain-containing protein 24 (Zinc finger protein 450) | May be involved in BMP2-induced transcription. {ECO:0000250}. |
| O43167 | ZBTB24 | S278 | ochoa | Zinc finger and BTB domain-containing protein 24 (Zinc finger protein 450) | May be involved in BMP2-induced transcription. {ECO:0000250}. |
| O43172 | PRPF4 | S185 | ochoa | U4/U6 small nuclear ribonucleoprotein Prp4 (PRP4 homolog) (hPrp4) (U4/U6 snRNP 60 kDa protein) (WD splicing factor Prp4) | Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). {ECO:0000269|PubMed:25383878, ECO:0000269|PubMed:28781166}. |
| O43194 | GPR39 | S256 | ochoa | G-protein coupled receptor 39 | Zinc-sensing receptor that can sense changes in extracellular Zn(2+), mediate Zn(2+) signal transmission, and participates in the regulation of numerous physiological processes including glucose homeostasis regulation, gastrointestinal mobility, hormone secretion and cell death (PubMed:18180304). Activation by Zn(2+) in keratinocytes increases the intracellular concentration of Ca(2+) and activates the ERK/MAPK and PI3K/AKT signaling pathways leading to epithelial repair (PubMed:20522546). Plays an essential role in normal wound healing by inducing the production of cytokines including the major inflammatory cytokine IL6 via the PKC/MAPK/CEBPB pathway (By similarity). Regulates adipose tissue metabolism, especially lipolysis, and regulates the function of lipases, such as hormone-sensitive lipase and adipose triglyceride lipase (By similarity). Plays a role in the inhibition of cell death and protects against oxidative, endoplasmic reticulum and mitochondrial stress by inducing secretion of the cytoprotective pigment epithelium-derived growth factor (PEDF) and probably other protective transcripts in a GNA13/RHOA/SRE-dependent manner (PubMed:18180304). Forms dynamic heteroreceptor complexes with HTR1A and GALR1 depending on cell type or specific physiological states, resulting in signaling diversity: HTR1A-GPR39 shows additive increase in signaling along the serum response element (SRE) and NF-kappa-B pathways while GALR1 acts as an antagonist blocking SRE (PubMed:26365466). {ECO:0000250|UniProtKB:Q5U431, ECO:0000269|PubMed:18180304, ECO:0000269|PubMed:20522546, ECO:0000269|PubMed:26365466}. |
| O43290 | SART1 | S437 | ochoa | U4/U6.U5 tri-snRNP-associated protein 1 (SNU66 homolog) (hSnu66) (Squamous cell carcinoma antigen recognized by T-cells 1) (SART-1) (hSART-1) (U4/U6.U5 tri-snRNP-associated 110 kDa protein) (allergen Hom s 1) | Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA. {ECO:0000269|PubMed:11350945, ECO:0000269|PubMed:25092792}. |
| O43294 | TGFB1I1 | S203 | ochoa | Transforming growth factor beta-1-induced transcript 1 protein (Androgen receptor coactivator 55 kDa protein) (Androgen receptor-associated protein of 55 kDa) (Hydrogen peroxide-inducible clone 5 protein) (Hic-5) | Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity. {ECO:0000269|PubMed:10075738, ECO:0000269|PubMed:11463817, ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12445807, ECO:0000269|PubMed:12700349, ECO:0000269|PubMed:15211577, ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:16141357, ECO:0000269|PubMed:16624805, ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536, ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9032249}. |
| O43294 | TGFB1I1 | S403 | ochoa|psp | Transforming growth factor beta-1-induced transcript 1 protein (Androgen receptor coactivator 55 kDa protein) (Androgen receptor-associated protein of 55 kDa) (Hydrogen peroxide-inducible clone 5 protein) (Hic-5) | Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity. {ECO:0000269|PubMed:10075738, ECO:0000269|PubMed:11463817, ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12445807, ECO:0000269|PubMed:12700349, ECO:0000269|PubMed:15211577, ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:16141357, ECO:0000269|PubMed:16624805, ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536, ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9032249}. |
| O43295 | SRGAP3 | S919 | ochoa | SLIT-ROBO Rho GTPase-activating protein 3 (srGAP3) (Mental disorder-associated GAP) (Rho GTPase-activating protein 14) (WAVE-associated Rac GTPase-activating protein) (WRP) | GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons. {ECO:0000269|PubMed:12195014, ECO:0000269|PubMed:12447388}. |
| O43314 | PPIP5K2 | S1180 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}. |
| O43318 | MAP3K7 | S192 | psp | Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}. |
| O43318 | MAP3K7 | S363 | ochoa | Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}. |
| O43353 | RIPK2 | S401 | ochoa | Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. |
| O43379 | WDR62 | S614 | ochoa | WD repeat-containing protein 62 | Required for cerebral cortical development. Plays a role in neuronal proliferation and migration (PubMed:20729831, PubMed:20890278). Plays a role in mother-centriole-dependent centriole duplication; the function also seems to involve CEP152, CDK5RAP2 and CEP63 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). {ECO:0000269|PubMed:20729831, ECO:0000269|PubMed:20890278, ECO:0000269|PubMed:26297806}. |
| O43390 | HNRNPR | S23 | ochoa | Heterogeneous nuclear ribonucleoprotein R (hnRNP R) | Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus. |
| O43399 | TPD52L2 | S149 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43399 | TPD52L2 | S186 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43426 | SYNJ1 | S579 | ochoa | Synaptojanin-1 (EC 3.1.3.36) (Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1) | Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:23804563, PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity). {ECO:0000250|UniProtKB:O18964, ECO:0000250|UniProtKB:Q62910, ECO:0000269|PubMed:23804563, ECO:0000269|PubMed:27435091}. |
| O43526 | KCNQ2 | S52 | psp | Potassium voltage-gated channel subfamily KQT member 2 (KQT-like 2) (Neuroblastoma-specific potassium channel subunit alpha KvLQT2) (Voltage-gated potassium channel subunit Kv7.2) | Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:24277843, PubMed:28793216, PubMed:9836639). M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers (PubMed:10781098, PubMed:14534157, PubMed:32884139, PubMed:37857637, PubMed:9836639). The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs (PubMed:14534157, PubMed:28793216, PubMed:9836639). KCNQ2-KCNQ3 M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) (PubMed:28793216). M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) (PubMed:28793216). Suppressed by activation of the muscarinic acetylcholine receptor CHRM1 (PubMed:10684873, PubMed:10713961). {ECO:0000269|PubMed:10684873, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:10781098, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:24277843, ECO:0000269|PubMed:28793216, ECO:0000269|PubMed:32884139, ECO:0000269|PubMed:37857637, ECO:0000269|PubMed:9836639}. |
| O43561 | LAT | S35 | ochoa | Linker for activation of T-cells family member 1 (36 kDa phosphotyrosine adapter protein) (pp36) (p36-38) | Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. {ECO:0000269|PubMed:10072481, ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:25907557}. |
| O43609 | SPRY1 | S50 | ochoa | Protein sprouty homolog 1 (Spry-1) | Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q9QXV9}. |
| O43639 | NCK2 | S104 | ochoa | Cytoplasmic protein NCK2 (Growth factor receptor-bound protein 4) (NCK adaptor protein 2) (Nck-2) (SH2/SH3 adaptor protein NCK-beta) | Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16835242}. |
| O43660 | PLRG1 | S391 | ochoa | Pleiotropic regulator 1 | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28076346, PubMed:28502770). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing (PubMed:11101529, PubMed:11544257). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000305|PubMed:33509932}. |
| O43663 | PRC1 | S554 | ochoa | Protein regulator of cytokinesis 1 | Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}. |
| O43795 | MYO1B | S1027 | ochoa | Unconventional myosin-Ib (MYH-1c) (Myosin I alpha) (MMI-alpha) (MMIa) | Motor protein that may participate in process critical to neuronal development and function such as cell migration, neurite outgrowth and vesicular transport. {ECO:0000250}. |
| O43815 | STRN | S503 | ochoa | Striatin | Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (Probable). {ECO:0000269|PubMed:18782753, ECO:0000305|PubMed:26876214}. |
| O43819 | SCO2 | S194 | ochoa | Protein SCO2 homolog, mitochondrial | Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2) by facilitating the incorporation of copper into the Cu(A) site of MT-CO2/COX2 (PubMed:15229189, PubMed:17189203, PubMed:19336478). Could also act as a thiol-disulfide oxidoreductase to regulate the redox state of the cysteines in SCO1 during maturation of MT-CO2/COX2 (PubMed:19336478). {ECO:0000269|PubMed:15229189, ECO:0000269|PubMed:17189203, ECO:0000269|PubMed:19336478}. |
| O43933 | PEX1 | S1172 | ochoa | Peroxisomal ATPase PEX1 (EC 3.6.4.-) (Peroxin-1) (Peroxisome biogenesis disorder protein 1) (Peroxisome biogenesis factor 1) | Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:11439091, PubMed:16314507, PubMed:16854980, PubMed:21362118, PubMed:29884772). Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (PubMed:29884772). Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5 (PubMed:29884772). {ECO:0000269|PubMed:11439091, ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:16854980, ECO:0000269|PubMed:21362118, ECO:0000269|PubMed:29884772}. |
| O60237 | PPP1R12B | S447 | ochoa | Protein phosphatase 1 regulatory subunit 12B (Myosin phosphatase-targeting subunit 2) (Myosin phosphatase target subunit 2) | Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus. {ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:9570949}. |
| O60271 | SPAG9 | S185 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60271 | SPAG9 | S705 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60271 | SPAG9 | S1262 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60315 | ZEB2 | S36 | ochoa | Zinc finger E-box-binding homeobox 2 (Smad-interacting protein 1) (SMADIP1) (Zinc finger homeobox protein 1b) | Transcriptional inhibitor that binds to DNA sequence 5'-CACCT-3' in different promoters (PubMed:16061479, PubMed:20516212). Represses transcription of E-cadherin (PubMed:16061479). Represses expression of MEOX2 (PubMed:20516212). {ECO:0000269|PubMed:16061479, ECO:0000269|PubMed:20516212}. |
| O60337 | MARCHF6 | S31 | ochoa | E3 ubiquitin-protein ligase MARCHF6 (EC 2.3.2.27) (Doa10 homolog) (Membrane-associated RING finger protein 6) (Membrane-associated RING-CH protein VI) (MARCH-VI) (Protein TEB-4) (RING finger protein 176) (RING-type E3 ubiquitin transferase MARCHF6) | Endoplasmic reticulum membrane-associated E3 ubiquitin ligase that plays a critical role in mitigating endoplasmic reticulum stress, the regulation of cholesterol and lipid homeostasis, and ferroptosis (PubMed:25088257, PubMed:35941365, PubMed:39216628). Acts as a pivotal component of both the Ac/N-degron pathway (targeting the N-terminal acetyl group of substrates) and the ER-associated protein degradation-cytosol (ERAD-C) pathway (targeting misfolded substrates) (PubMed:30425097, PubMed:35941365). For instance, mediates the degradation of Ac/N-degron-bearing proteins such as the G-protein regulator RGS2 and the lipid droplet protein PLIN2 (PubMed:39216628). Suppresses endoplasmic reticulum stress and ferroptosis through cytosolic POMC degradation (By similarity). Prevents ferroptosis by acting as a NADPH sensor during lipid peroxidation through its C-terminal regulatory region (PubMed:35941365). Facilitates also the degradation of selected endoplasmic reticulum proteins by associating with signal peptide peptidase for the turnover of endogenous tail-anchored proteins (PubMed:29519897). Promotes ubiquitination of DIO2, leading to its degradation (PubMed:19651899). By ubiquitinating and thereby modulating the stability of many proteins of the cholesterol pathway including SQLE, CYP51A1, CYP11A1 and HMGCR, acts as a crucial post-translational regulator of cholesterol synthesis (PubMed:24449766, PubMed:31904814, PubMed:36958722). {ECO:0000250|UniProtKB:Q6ZQ89, ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:19651899, ECO:0000269|PubMed:24449766, ECO:0000269|PubMed:25088257, ECO:0000269|PubMed:29519897, ECO:0000269|PubMed:30425097, ECO:0000269|PubMed:31904814, ECO:0000269|PubMed:35941365, ECO:0000269|PubMed:36958722, ECO:0000269|PubMed:39216628}. |
| O60341 | KDM1A | S683 | psp | Lysine-specific histone demethylase 1A (EC 1.14.99.66) (BRAF35-HDAC complex protein BHC110) (Flavin-containing amine oxidase domain-containing protein 2) ([histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A) | Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:16079795, PubMed:16140033, PubMed:16223729, PubMed:27292636). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16079794, PubMed:16140033). Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636). Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). Required for the repression of GIPR expression (PubMed:34655521, PubMed:34906447). {ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:15620353, ECO:0000269|PubMed:15811342, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:16140033, ECO:0000269|PubMed:16223729, ECO:0000269|PubMed:16885027, ECO:0000269|PubMed:16956976, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:23721412, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:29358331, ECO:0000269|PubMed:29691401, ECO:0000269|PubMed:34655521, ECO:0000269|PubMed:34906447}. |
| O60353 | FZD6 | S683 | ochoa | Frizzled-6 (Fz-6) (hFz6) | Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q61089}. |
| O60437 | PPL | S949 | ochoa | Periplakin (190 kDa paraneoplastic pemphigus antigen) (195 kDa cornified envelope precursor protein) | Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling. {ECO:0000269|PubMed:9412476}. |
| O60506 | SYNCRIP | S587 | ochoa | Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) (Glycine- and tyrosine-rich RNA-binding protein) (GRY-RBP) (NS1-associated protein 1) (Synaptotagmin-binding, cytoplasmic RNA-interacting protein) | Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; seems not to be essential for GAIT complex function. {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:11134005, ECO:0000269|PubMed:11352648, ECO:0000269|PubMed:11574476, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:23071094}. |
| O60563 | CCNT1 | S340 | ochoa | Cyclin-T1 (CycT1) (Cyclin-T) | Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:35393539}.; FUNCTION: (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. {ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10329126}. |
| O60664 | PLIN3 | S217 | ochoa | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| O60701 | UGDH | S275 | ochoa | UDP-glucose 6-dehydrogenase (UDP-Glc dehydrogenase) (UDP-GlcDH) (UDPGDH) (EC 1.1.1.22) | Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21502315, PubMed:21961565, PubMed:22123821, PubMed:23106432, PubMed:25478983, PubMed:27966912, PubMed:30420606, PubMed:30457329). Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (By similarity). Required for proper brain and neuronal development (PubMed:32001716). {ECO:0000250|UniProtKB:O70475, ECO:0000269|PubMed:21502315, ECO:0000269|PubMed:21961565, ECO:0000269|PubMed:22123821, ECO:0000269|PubMed:23106432, ECO:0000269|PubMed:25478983, ECO:0000269|PubMed:27966912, ECO:0000269|PubMed:30420606, ECO:0000269|PubMed:30457329, ECO:0000269|PubMed:32001716}. |
| O60716 | CTNND1 | S225 | ochoa | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60716 | CTNND1 | S895 | ochoa | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60741 | HCN1 | S116 | psp | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 (Brain cyclic nucleotide-gated channel 1) (BCNG-1) | Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions (PubMed:15351778, PubMed:28086084). Displays lower selectivity for K(+) over Na(+) ions (PubMed:28086084). Contributes to the native pacemaker currents in heart (If) and in the generation of the I(h) current which controls neuron excitability (PubMed:29936235, PubMed:30351409). Participates in cerebellar mechanisms of motor learning (By similarity). May mediate responses to sour stimuli (By similarity). {ECO:0000250|UniProtKB:O88704, ECO:0000269|PubMed:15351778, ECO:0000269|PubMed:28086084, ECO:0000269|PubMed:29936235, ECO:0000269|PubMed:30351409}. |
| O60814 | H2BC12 | S57 | ochoa | Histone H2B type 1-K (H2B K) (HIRA-interacting protein 1) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.; FUNCTION: Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid. |
| O60825 | PFKFB2 | S32 | psp | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (6PF-2-K/Fru-2,6-P2ase 2) (PFK/FBPase 2) (6PF-2-K/Fru-2,6-P2ase heart-type isozyme) [Includes: 6-phosphofructo-2-kinase (EC 2.7.1.105); Fructose-2,6-bisphosphatase (EC 3.1.3.46)] | Synthesis and degradation of fructose 2,6-bisphosphate. {ECO:0000269|PubMed:11069105}. |
| O60832 | DKC1 | S170 | ochoa | H/ACA ribonucleoprotein complex subunit DKC1 (EC 5.4.99.-) (CBF5 homolog) (Dyskerin) (Nopp140-associated protein of 57 kDa) (Nucleolar protein NAP57) (Nucleolar protein family A member 4) (snoRNP protein DKC1) | [Isoform 1]: Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674, PubMed:32554502). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:25219674, ECO:0000269|PubMed:32554502}.; FUNCTION: [Isoform 3]: Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression. {ECO:0000269|PubMed:21820037}. |
| O60888 | CUTA | S48 | ochoa | Protein CutA (Acetylcholinesterase-associated protein) (Brain acetylcholinesterase putative membrane anchor) | May form part of a complex of membrane proteins attached to acetylcholinesterase (AChE). |
| O75044 | SRGAP2 | S845 | ochoa | SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) (Formin-binding protein 2) (Rho GTPase-activating protein 34) | Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:20810653, PubMed:27373832, PubMed:28333212). Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (By similarity). Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:27373832). Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (By similarity). In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:20810653, PubMed:21148482). {ECO:0000250|UniProtKB:Q91Z67, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944, ECO:0000269|PubMed:27373832, ECO:0000269|PubMed:28333212}. |
| O75052 | NOS1AP | S249 | ochoa | Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (C-terminal PDZ ligand of neuronal nitric oxide synthase protein) (Nitric oxide synthase 1 adaptor protein) | Adapter protein involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1. The complex formed with NOS1 and synapsins is necessary for specific NO and synapsin functions at a presynaptic level. Mediates an indirect interaction between NOS1 and RASD1 leading to enhance the ability of NOS1 to activate RASD1. Competes with DLG4 for interaction with NOS1, possibly affecting NOS1 activity by regulating the interaction between NOS1 and DLG4 (By similarity). In kidney podocytes, plays a role in podosomes and filopodia formation through CDC42 activation (PubMed:33523862). {ECO:0000250|UniProtKB:O54960, ECO:0000269|PubMed:33523862}. |
| O75116 | ROCK2 | S1137 | ochoa | Rho-associated protein kinase 2 (EC 2.7.11.1) (Rho kinase 2) (Rho-associated, coiled-coil-containing protein kinase 2) (Rho-associated, coiled-coil-containing protein kinase II) (ROCK-II) (p164 ROCK-2) | Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10579722, ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}. |
| O75122 | CLASP2 | S1092 | psp | CLIP-associating protein 2 (Cytoplasmic linker-associated protein 2) (Protein Orbit homolog 2) (hOrbit2) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules (PubMed:26003921). Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2 (PubMed:16824950). This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (PubMed:16866869, PubMed:16914514). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16824950, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:26003921}. |
| O75128 | COBL | S566 | ochoa | Protein cordon-bleu | Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. {ECO:0000250, ECO:0000269|PubMed:21816349}. |
| O75145 | PPFIA3 | S537 | ochoa | Liprin-alpha-3 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-3) (PTPRF-interacting protein alpha-3) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:9624153}. |
| O75154 | RAB11FIP3 | S348 | psp | Rab11 family-interacting protein 3 (FIP3) (FIP3-Rab11) (Rab11-FIP3) (Arfophilin-1) (EF hands-containing Rab-interacting protein) (Eferin) (MU-MB-17.148) | Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery (PubMed:15601896, PubMed:16148947, PubMed:17394487, PubMed:17628206, PubMed:18511905, PubMed:19327867, PubMed:20026645, PubMed:25673879, PubMed:26258637, PubMed:31204173). Recruited by Rab11 to endosomes where it links Rab11 to dynein motor complex (PubMed:20026645). The functional Rab11-RAB11FIP3-dynein complex regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endocytic recycling compartment (ERC) during interphase of cell cycle (PubMed:17394487, PubMed:20026645). Facilitates the interaction between dynein and dynactin and activates dynein processivity (PubMed:25035494). Binding with ASAP1 is needed to regulate the pericentrosomal localization of recycling endosomes (By similarity). The Rab11-RAB11FIP3 complex is also implicated in the transport during telophase of vesicles derived from recycling endosomes to the cleavage furrow via centrosome-anchored microtubules, where the vesicles function to deliver membrane during late cytokinesis and abscission (PubMed:15601896, PubMed:16148947). The recruitment of Rab11-RAB11FIP3-containing endosomes to the cleavage furrow and tethering to the midbody is co-mediated by RAB11FIP3 interaction with ARF6-exocyst and RACGAP1-MKLP1 tethering complexes (PubMed:17628206, PubMed:18511905). Also involved in the Rab11-Rabin8-Rab8 ciliogenesis cascade by facilitating the orderly assembly of a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which directs preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:26258637, PubMed:31204173). Also promotes the activity of Rab11 and ASAP1 in the ARF4-dependent Golgi-to-cilia transport of the sensory receptor rhodopsin (PubMed:25673879). Competes with WDR44 for binding to Rab11, which controls intracellular ciliogenesis pathway (PubMed:31204173). May play a role in breast cancer cell motility by regulating actin cytoskeleton (PubMed:19327867). {ECO:0000250|UniProtKB:Q8CHD8, ECO:0000269|PubMed:15601896, ECO:0000269|PubMed:16148947, ECO:0000269|PubMed:17394487, ECO:0000269|PubMed:17628206, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19327867, ECO:0000269|PubMed:20026645, ECO:0000269|PubMed:25035494, ECO:0000269|PubMed:25673879, ECO:0000269|PubMed:26258637, ECO:0000269|PubMed:31204173}. |
| O75161 | NPHP4 | S868 | ochoa | Nephrocystin-4 (Nephroretinin) | Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module (PubMed:19755384, PubMed:21565611). Does not seem to be strictly required for ciliogenesis (PubMed:21565611). Required for building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells. Seems to recruit INT to basal bodies of motile cilia which subsequently interacts with actin-modifying proteins such as DAAM1 (By similarity). In cooperation with INVS may down-regulate the canonical Wnt pathway and promote the Wnt-PCP pathway by regulating expression and subcellular location of disheveled proteins. Stabilizes protein levels of JADE1 and promotes its translocation to the nucleus leading to cooperative inhibition of canonical Wnt signaling (PubMed:21498478, PubMed:22654112). Acts as a negative regulator of the hippo pathway by association with LATS1 and modifying LATS1-dependent phosphorylation and localization of WWTR1/TAZ (PubMed:21555462). {ECO:0000250|UniProtKB:B0DOB4, ECO:0000250|UniProtKB:P59240, ECO:0000269|PubMed:21498478, ECO:0000269|PubMed:21555462, ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:22654112, ECO:0000305|PubMed:19755384}. |
| O75362 | ZNF217 | S654 | ochoa | Zinc finger protein 217 | Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}. |
| O75369 | FLNB | S518 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75369 | FLNB | S658 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75369 | FLNB | S1433 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75376 | NCOR1 | S1143 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75376 | NCOR1 | S2380 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75379 | VAMP4 | S17 | ochoa | Vesicle-associated membrane protein 4 (VAMP-4) | Involved in the pathway that functions to remove an inhibitor (probably synaptotagmin-4) of calcium-triggered exocytosis during the maturation of secretory granules. May be a marker for this sorting pathway that is critical for remodeling the secretory response of granule. |
| O75410 | TACC1 | S568 | ochoa | Transforming acidic coiled-coil-containing protein 1 (Gastric cancer antigen Ga55) (Taxin-1) | Involved in transcription regulation induced by nuclear receptors, including in T3 thyroid hormone and all-trans retinoic acid pathways (PubMed:20078863). Might promote the nuclear localization of the receptors (PubMed:20078863). Likely involved in the processes that promote cell division prior to the formation of differentiated tissues. {ECO:0000269|PubMed:20078863}. |
| O75420 | GIGYF1 | S21 | ochoa | GRB10-interacting GYF protein 1 (PERQ amino acid-rich with GYF domain-containing protein 1) | May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:12771153}. |
| O75427 | LRCH4 | S309 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 4 (Leucine-rich repeat neuronal protein 4) (Leucine-rich neuronal protein) | Accessory protein that regulates signaling by multiple TLRs, acting as a broad-spanning regulator of the innate immune response. In macrophages, binds LPS and promotes proper docking of LPS in lipid raft membrane. May be required for lipid raft maintenance. {ECO:0000250|UniProtKB:Q921G6}. |
| O75469 | NR1I2 | S221 | psp | Nuclear receptor subfamily 1 group I member 2 (Orphan nuclear receptor PAR1) (Orphan nuclear receptor PXR) (Pregnane X receptor) (Steroid and xenobiotic receptor) (SXR) | Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes. {ECO:0000269|PubMed:11297522, ECO:0000269|PubMed:11668216, ECO:0000269|PubMed:12578355, ECO:0000269|PubMed:18768384, ECO:0000269|PubMed:19297428, ECO:0000269|PubMed:9727070}. |
| O75494 | SRSF10 | S23 | ochoa | Serine/arginine-rich splicing factor 10 (40 kDa SR-repressor protein) (SRrp40) (FUS-interacting serine-arginine-rich protein 1) (Splicing factor SRp38) (Splicing factor, arginine/serine-rich 13A) (TLS-associated protein with Ser-Arg repeats) (TASR) (TLS-associated protein with SR repeats) (TLS-associated serine-arginine protein) (TLS-associated SR protein) | Splicing factor that in its dephosphorylated form acts as a general repressor of pre-mRNA splicing (PubMed:11684676, PubMed:12419250, PubMed:14765198). Seems to interfere with the U1 snRNP 5'-splice recognition of SNRNP70 (PubMed:14765198). Required for splicing repression in M-phase cells and after heat shock (PubMed:14765198). Also acts as a splicing factor that specifically promotes exon skipping during alternative splicing (PubMed:26876937). Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May be involved in regulation of alternative splicing in neurons, with isoform 1 acting as a positive and isoform 3 as a negative regulator (PubMed:12419250). {ECO:0000269|PubMed:11684676, ECO:0000269|PubMed:12419250, ECO:0000269|PubMed:14765198, ECO:0000269|PubMed:26876937}. |
| O75521 | ECI2 | S101 | ochoa | Enoyl-CoA delta isomerase 2 (EC 5.3.3.8) (DRS-1) (Delta(3),delta(2)-enoyl-CoA isomerase) (D3,D2-enoyl-CoA isomerase) (Diazepam-binding inhibitor-related protein 1) (DBI-related protein 1) (Dodecenoyl-CoA isomerase) (Hepatocellular carcinoma-associated antigen 88) (Peroxisomal 3,2-trans-enoyl-CoA isomerase) (pECI) (Renal carcinoma antigen NY-REN-1) | Able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species. Has a preference for 3-trans substrates. {ECO:0000269|PubMed:10419495}. |
| O75533 | SF3B1 | S242 | ochoa | Splicing factor 3B subunit 1 (Pre-mRNA-splicing factor SF3b 155 kDa subunit) (SF3b155) (Spliceosome-associated protein 155) (SAP 155) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B1 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92 (By similarity). {ECO:0000250|UniProtKB:Q99NB9, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| O75533 | SF3B1 | S308 | ochoa | Splicing factor 3B subunit 1 (Pre-mRNA-splicing factor SF3b 155 kDa subunit) (SF3b155) (Spliceosome-associated protein 155) (SAP 155) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B1 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92 (By similarity). {ECO:0000250|UniProtKB:Q99NB9, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| O75569 | PRKRA | S130 | ochoa | Interferon-inducible double-stranded RNA-dependent protein kinase activator A (PKR-associated protein X) (PKR-associating protein X) (Protein activator of the interferon-induced protein kinase) (Protein kinase, interferon-inducible double-stranded RNA-dependent activator) | Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner (By similarity). {ECO:0000250, ECO:0000269|PubMed:10336432, ECO:0000269|PubMed:11238927, ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:16982605, ECO:0000269|PubMed:17452327, ECO:0000269|PubMed:9687506}. |
| O75569 | PRKRA | S287 | psp | Interferon-inducible double-stranded RNA-dependent protein kinase activator A (PKR-associated protein X) (PKR-associating protein X) (Protein activator of the interferon-induced protein kinase) (Protein kinase, interferon-inducible double-stranded RNA-dependent activator) | Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner (By similarity). {ECO:0000250, ECO:0000269|PubMed:10336432, ECO:0000269|PubMed:11238927, ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:16982605, ECO:0000269|PubMed:17452327, ECO:0000269|PubMed:9687506}. |
| O75688 | PPM1B | S195 | ochoa|psp | Protein phosphatase 1B (EC 3.1.3.16) (Protein phosphatase 2C isoform beta) (PP2C-beta) | Enzyme with a broad specificity. Dephosphorylates CDK2 and CDK6 in vitro. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser-172'. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:18930133, ECO:0000269|PubMed:22750291}. |
| O75716 | STK16 | S197 | psp | Serine/threonine-protein kinase 16 (EC 2.7.11.1) (Myristoylated and palmitoylated serine/threonine-protein kinase) (MPSK) (Protein kinase PKL12) (TGF-beta-stimulated factor 1) (TSF-1) (Tyrosine-protein kinase STK16) (EC 2.7.10.2) (hPSK) | Membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. Also autophosphorylates. May be involved in secretory vesicle trafficking or intracellular signaling. May have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. May be involved in TGF-beta signaling. Able to autophosphorylate on Tyr residue; it is however unclear whether it has tyrosine-protein kinase toward other proteins. {ECO:0000269|PubMed:10364453}. |
| O75717 | WDHD1 | S407 | ochoa | WD repeat and HMG-box DNA-binding protein 1 (Acidic nucleoplasmic DNA-binding protein 1) (And-1) | Core replisome component that acts as a replication initiation factor. Binds directly to the CMG complex and functions as a hub to recruit additional proteins to the replication fork. {ECO:0000269|PubMed:19805216, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| O75762 | TRPA1 | S428 | psp | Transient receptor potential cation channel subfamily A member 1 (Ankyrin-like with transmembrane domains protein 1) (Transformation-sensitive protein p120) (p120) (Wasabi receptor) | Ligand-activated Ca(2+)-permeable, nonselective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function (PubMed:17259981, PubMed:21195050, PubMed:21873995, PubMed:23199233, PubMed:25389312, PubMed:33152265). Has a relatively high Ca(2+) selectivity, with a preference for divalent over monovalent cations (Ca(2+) > Ba(2+) > Mg(2+) > NH4(+) > Li(+) > K(+)), the influx of cation into the cytoplasm leads to membrane depolarization (PubMed:19202543, PubMed:21195050). Has a central role in the pain response to endogenous inflammatory mediators, such as bradykinin and to a diverse array of irritants. Activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an environmental irritant (PubMed:20547126, PubMed:25389312, PubMed:27241698, PubMed:30878828). Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner (PubMed:17164327, PubMed:27241698, PubMed:31866091, PubMed:32641835). Non-electrophile agonists bind at distinct sites in the transmembrane domain to promote channel activation (PubMed:33152265). Also acts as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds (By similarity). {ECO:0000250|UniProtKB:Q8BLA8, ECO:0000269|PubMed:17164327, ECO:0000269|PubMed:17259981, ECO:0000269|PubMed:19202543, ECO:0000269|PubMed:20547126, ECO:0000269|PubMed:21195050, ECO:0000269|PubMed:21873995, ECO:0000269|PubMed:23199233, ECO:0000269|PubMed:25389312, ECO:0000269|PubMed:27241698, ECO:0000269|PubMed:30878828, ECO:0000269|PubMed:31866091, ECO:0000269|PubMed:32641835, ECO:0000269|PubMed:33152265}. |
| O75792 | RNASEH2A | S277 | ochoa | Ribonuclease H2 subunit A (RNase H2 subunit A) (EC 3.1.26.4) (Aicardi-Goutieres syndrome 4 protein) (AGS4) (RNase H(35)) (Ribonuclease HI large subunit) (RNase HI large subunit) (Ribonuclease HI subunit A) | Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:21177858}. |
| O75815 | BCAR3 | S317 | ochoa | Breast cancer anti-estrogen resistance protein 3 (Novel SH2-containing protein 2) (SH2 domain-containing protein 3B) | Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:24216110). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (PubMed:24216110). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:19086031). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (By similarity). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis (PubMed:18722344). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (By similarity). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By similarity). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By similarity). However, in a contrasting study, lacks GEF activity towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5, ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014, ECO:0000269|PubMed:24216110}. |
| O75891 | ALDH1L1 | S629 | ochoa | Cytosolic 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH) (FDH) (EC 1.5.1.6) (Aldehyde dehydrogenase family 1 member L1) | Cytosolic 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide (PubMed:19933275, PubMed:21238436). May also have an NADP(+)-dependent aldehyde dehydrogenase activity towards formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde (By similarity). {ECO:0000250|UniProtKB:P28037, ECO:0000269|PubMed:19933275, ECO:0000269|PubMed:21238436}. |
| O75962 | TRIO | S520 | ochoa | Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein) | Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity). {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}. |
| O75976 | CPD | S1035 | ochoa | Carboxypeptidase D (EC 3.4.17.22) (Metallocarboxypeptidase D) (gp180) | None |
| O76080 | ZFAND5 | S82 | ochoa | AN1-type zinc finger protein 5 (Zinc finger A20 domain-containing protein 2) (Zinc finger protein 216) | Involved in protein degradation via the ubiquitin-proteasome system. May act by anchoring ubiquitinated proteins to the proteasome. Plays a role in ubiquitin-mediated protein degradation during muscle atrophy. Plays a role in the regulation of NF-kappa-B activation and apoptosis. Inhibits NF-kappa-B activation triggered by overexpression of RIPK1 and TRAF6 but not of RELA. Also inhibits tumor necrosis factor (TNF), IL-1 and TLR4-induced NF-kappa-B activation in a dose-dependent manner. Overexpression sensitizes cells to TNF-induced apoptosis. Is a potent inhibitory factor for osteoclast differentiation. {ECO:0000269|PubMed:14754897}. |
| O94823 | ATP10B | S984 | ochoa | Phospholipid-transporting ATPase VB (EC 7.6.2.1) (ATPase class V type 10B) (P4-ATPase flippase complex alpha subunit ATP10B) | Catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of lysosome membranes. Plays an important role in the maintenance of lysosome membrane integrity and function in cortical neurons. {ECO:0000269|PubMed:32172343}. |
| O94826 | TOMM70 | S96 | ochoa | Mitochondrial import receptor subunit TOM70 (Mitochondrial precursor proteins import receptor) (Translocase of outer membrane 70 kDa subunit) (Translocase of outer mitochondrial membrane protein 70) | Acts as a receptor of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) (PubMed:12526792). Recognizes and mediates the translocation of mitochondrial preproteins from the cytosol into the mitochondria in a chaperone dependent manner (PubMed:12526792, PubMed:35025629). Mediates TBK1 and IRF3 activation induced by MAVS in response to Sendai virus infection and promotes host antiviral responses during virus infection (PubMed:20628368, PubMed:25609812, PubMed:32728199). Upon Sendai virus infection, recruits HSP90AA1:IRF3:BAX in mitochondrion and the complex induces apoptosis (PubMed:25609812). {ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:32728199, ECO:0000269|PubMed:35025629}. |
| O94830 | DDHD2 | S183 | ochoa | Triacylglycerol hydrolase DDHD2 (TAG hydrolase) (EC 3.1.1.3) (DDHD domain-containing protein 2) (KIAA0725p) (Phospholipase DDHD2) (EC 3.1.1.-) (SAM, WWE and DDHD domain-containing protein 1) (Triglyceride hydrolase DDHD2) (Triglyceride lipase) | Diacylglycerol (DAG) and triacylglycerol (TAG) lipase required for proper lipid homeostasis in the central nervous system (PubMed:29278326, PubMed:37832604). It cooperates with PNPLA2/ATGL in neuronal TAG catabolism and hydrolyzes sn-1,3 DAG downstream of PNPLA2/ATGL (By similarity). In vitro, it also acts as a phospholipase that hydrolyzes preferentially phosphatidic acids, including 1,2-dioleoyl-sn-phosphatidic acid, phosphatidylcholine and phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P), phosphatidylinositol 5-phosphate (PI(5)P) and possibly phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in the maintenance of the endoplasmic reticulum and/or Golgi structures. May regulate the transport between Golgi apparatus and plasma membrane. {ECO:0000250|UniProtKB:Q80Y98, ECO:0000269|PubMed:11788596, ECO:0000269|PubMed:20932832, ECO:0000269|PubMed:22922100, ECO:0000269|PubMed:29278326, ECO:0000269|PubMed:37832604}. |
| O94832 | MYO1D | S971 | ochoa | Unconventional myosin-Id | Unconventional myosin that functions as actin-based motor protein with ATPase activity (By similarity). Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes (By similarity). Required for normal planar cell polarity in ciliated tracheal cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement in the trachea. Required for normal, polarized cilia organization in brain ependymal epithelial cells (By similarity). {ECO:0000250|UniProtKB:F1PRN2, ECO:0000250|UniProtKB:Q63357}. |
| O94868 | FCHSD2 | S190 | ochoa | F-BAR and double SH3 domains protein 2 (Carom) (Protein nervous wreck 1) (NWK1) (SH3 multiple domains protein 3) | Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor (PubMed:29887380). Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling (PubMed:30249660). Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits (PubMed:29887380). Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate (PubMed:29887380). When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex. Does not promote actin polymerisation in the absence of membranes (PubMed:29887380). {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}. |
| O94885 | SASH1 | S239 | ochoa | SAM and SH3 domain-containing protein 1 (Proline-glutamate repeat-containing protein) | Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}. |
| O94910 | ADGRL1 | S1129 | ochoa | Adhesion G protein-coupled receptor L1 (Calcium-independent alpha-latrotoxin receptor 1) (CIRL-1) (Latrophilin-1) (Lectomedin-2) | Calcium-independent receptor of high affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells (PubMed:35907405). Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization. Receptor probably implicated in the regulation of exocytosis (By similarity). {ECO:0000250|UniProtKB:O88917, ECO:0000269|PubMed:35907405}. |
| O94915 | FRYL | S1539 | ochoa | Protein furry homolog-like (ALL1-fused gene from chromosome 4p12 protein) | Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching (By similarity). May function as a transcriptional activator. {ECO:0000250, ECO:0000269|PubMed:16061630}. |
| O94916 | NFAT5 | S646 | ochoa | Nuclear factor of activated T-cells 5 (NF-AT5) (T-cell transcription factor NFAT5) (Tonicity-responsive enhancer-binding protein) (TonE-binding protein) (TonEBP) | Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394). Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:34049076). {ECO:0000269|PubMed:10051678, ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:22266867, ECO:0000269|PubMed:34049076}. |
| O94964 | MTCL2 | S931 | ochoa | Microtubule cross-linking factor 2 (SOGA family member 1) (Suppressor of glucose by autophagy) (Suppressor of glucose, autophagy-associated protein 1) [Cleaved into: N-terminal form; C-terminal 80 kDa form (80-kDa SOGA fragment)] | Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Preferentially acts on the perinuclear microtubules accumulated around the Golgi. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain (By similarity). Required for faithful chromosome segregation during mitosis (PubMed:33587225). Regulates autophagy by playing a role in the reduction of glucose production in an adiponectin- and insulin-dependent manner (By similarity). {ECO:0000250|UniProtKB:E1U8D0, ECO:0000269|PubMed:33587225}. |
| O94988 | FAM13A | S856 | ochoa | Protein FAM13A | None |
| O94992 | HEXIM1 | S66 | ochoa | Protein HEXIM1 (Cardiac lineage protein 1) (Estrogen down-regulated gene 1 protein) (Hexamethylene bis-acetamide-inducible protein 1) (Menage a quatre protein 1) | Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:14580347, PubMed:15201869, PubMed:15713661). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:12832472, PubMed:14580347, PubMed:15201869, PubMed:15713661). May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity (PubMed:15940264, PubMed:15941832, PubMed:17088550). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:12581153, ECO:0000269|PubMed:12832472, ECO:0000269|PubMed:14580347, ECO:0000269|PubMed:15201869, ECO:0000269|PubMed:15713661, ECO:0000269|PubMed:15940264, ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:17088550, ECO:0000269|PubMed:28712728}. |
| O95049 | TJP3 | S212 | ochoa | Tight junction protein ZO-3 (Tight junction protein 3) (Zona occludens protein 3) (Zonula occludens protein 3) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}. |
| O95071 | UBR5 | S90 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95071 | UBR5 | S174 | ochoa|psp | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95071 | UBR5 | S2434 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95163 | ELP1 | S251 | ochoa | Elongator complex protein 1 (ELP1) (IkappaB kinase complex-associated protein) (IKK complex-associated protein) (p150) | Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (By similarity). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (PubMed:9751059). {ECO:0000250|UniProtKB:Q06706, ECO:0000250|UniProtKB:Q7TT37, ECO:0000269|PubMed:9751059, ECO:0000303|PubMed:29332244}. |
| O95208 | EPN2 | S327 | ochoa | Epsin-2 (EPS-15-interacting protein 2) | Plays a role in the formation of clathrin-coated invaginations and endocytosis. {ECO:0000269|PubMed:10567358}. |
| O95235 | KIF20A | S556 | ochoa | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95235 | KIF20A | S754 | psp | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95271 | TNKS | S987 | psp | Poly [ADP-ribose] polymerase tankyrase-1 (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 5) (ARTD5) (Poly [ADP-ribose] polymerase 5A) (Protein poly-ADP-ribosyltransferase tankyrase-1) (EC 2.4.2.-) (TNKS-1) (TRF1-interacting ankyrin-related ADP-ribose polymerase) (Tankyrase I) (Tankyrase-1) (TANK1) | Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379, PubMed:28619731). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269|PubMed:10988299, ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:22864114, ECO:0000269|PubMed:23622245, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:28619731}. |
| O95278 | EPM2A | S25 | psp | Laforin (EC 3.1.3.-) (EC 3.1.3.16) (EC 3.1.3.48) (Glucan phosphatase) (Glycogen phosphatase) (Lafora PTPase) (LAFPTPase) | Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates (PubMed:16901901, PubMed:23922729, PubMed:25538239, PubMed:25544560, PubMed:26231210). Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro) (PubMed:11001928, PubMed:11220751, PubMed:11739371, PubMed:14532330, PubMed:14722920, PubMed:16971387, PubMed:18617530, PubMed:22036712, PubMed:23922729). Has been shown to dephosphorylate MAPT (By similarity). Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin (PubMed:23922729). Also promotes proteasome-independent protein degradation through the macroautophagy pathway (PubMed:20453062). {ECO:0000250|UniProtKB:Q9WUA5, ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:14722920, ECO:0000269|PubMed:16901901, ECO:0000269|PubMed:16971387, ECO:0000269|PubMed:18070875, ECO:0000269|PubMed:18617530, ECO:0000269|PubMed:19036738, ECO:0000269|PubMed:20453062, ECO:0000269|PubMed:22036712, ECO:0000269|PubMed:23624058, ECO:0000269|PubMed:23922729, ECO:0000269|PubMed:25538239, ECO:0000269|PubMed:25544560, ECO:0000269|PubMed:26231210}.; FUNCTION: [Isoform 2]: Does not bind to glycogen (PubMed:18617530). Lacks phosphatase activity and might function as a dominant-negative regulator for the phosphatase activity of isoform 1 and isoform 7 (PubMed:18617530, PubMed:22036712). {ECO:0000269|PubMed:18617530, ECO:0000269|PubMed:22036712}.; FUNCTION: [Isoform 7]: Has phosphatase activity (in vitro). {ECO:0000269|PubMed:22036712}. |
| O95376 | ARIH2 | S335 | ochoa | E3 ubiquitin-protein ligase ARIH2 (ARI-2) (Protein ariadne-2 homolog) (EC 2.3.2.31) (Triad1 protein) | E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655, PubMed:33268465, PubMed:34518685, PubMed:38418882). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (PubMed:33268465, PubMed:34518685, PubMed:38418882). The initial ubiquitin is then elongated (PubMed:33268465). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the cullin-5 (CUL5) component of the ECS complex (PubMed:24076655). Together with the ECS(ASB9) complex, catalyzes ubiquitination of CKB (PubMed:33268465). Promotes ubiquitination of DCUN1D1 (PubMed:30587576). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006). {ECO:0000269|PubMed:16118314, ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:30587576, ECO:0000269|PubMed:33268465, ECO:0000269|PubMed:34518685, ECO:0000269|PubMed:38418882}.; FUNCTION: (Microbial infection) Following infection by HIV-1 virus, acts together with a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, to catalyze ubiquitination and degradation of APOBEC3F and APOBEC3G. {ECO:0000269|PubMed:31253590, ECO:0000269|PubMed:36754086}. |
| O95400 | CD2BP2 | S39 | ochoa | CD2 antigen cytoplasmic tail-binding protein 2 (CD2 cytoplasmic domain-binding protein 2) (CD2 tail-binding protein 2) (U5 snRNP 52K protein) (U5-52K) | Involved in pre-mRNA splicing as component of the U5 snRNP complex that is involved in spliceosome assembly. {ECO:0000269|PubMed:15840814}. |
| O95425 | SVIL | S905 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95425 | SVIL | S938 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95428 | PAPLN | S17 | ochoa | Papilin | None |
| O95544 | NADK | S55 | ochoa | NAD kinase (EC 2.7.1.23) (Poly(P)/ATP NAD kinase) | None |
| O95684 | CEP43 | S326 | ochoa | Centrosomal protein 43 (FGFR1 oncogene partner) | Required for anchoring microtubules to the centrosomes (PubMed:16314388, PubMed:28659385). Required for ciliation (PubMed:28625565, PubMed:28659385). {ECO:0000269|PubMed:16314388, ECO:0000269|PubMed:28625565, ECO:0000269|PubMed:28659385}. |
| O95716 | RAB3D | S199 | ochoa | Ras-related protein Rab-3D (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). RAB3D may be involved in the insulin-induced exocytosis of GLUT4-containing vesicles in adipocytes (By similarity). {ECO:0000250|UniProtKB:P20336, ECO:0000250|UniProtKB:P35276}. |
| O95747 | OXSR1 | S510 | ochoa | Serine/threonine-protein kinase OSR1 (EC 2.7.11.1) (Oxidative stress-responsive 1 protein) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:17721439, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:17721439). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (PubMed:23386621, PubMed:25362046). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (PubMed:29581290). Phosphorylates RELL1, RELL2 and RELT (PubMed:16389068, PubMed:28688764). Phosphorylates PAK1 (PubMed:14707132). Phosphorylates PLSCR1 in the presence of RELT (PubMed:22052202). {ECO:0000269|PubMed:14707132, ECO:0000269|PubMed:16389068, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:17721439, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:23386621, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:28688764, ECO:0000269|PubMed:29581290, ECO:0000269|PubMed:34289367}. |
| O95757 | HSPA4L | S579 | ochoa | Heat shock 70 kDa protein 4L (Heat shock 70-related protein APG-1) (Heat shock protein family H member 3) (Heat-shock protein family A member 4-like protein) (HSPA4-like protein) (Osmotic stress protein 94) | Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. {ECO:0000250}. |
| O95759 | TBC1D8 | S1035 | ochoa | TBC1 domain family member 8 (AD 3) (Vascular Rab-GAP/TBC-containing protein) | May act as a GTPase-activating protein for Rab family protein(s). |
| O95785 | WIZ | S1121 | ochoa | Protein Wiz (Widely-interspaced zinc finger-containing protein) (Zinc finger protein 803) | May link EHMT1 and EHMT2 histone methyltransferases to the CTBP corepressor machinery. May be involved in EHMT1-EHMT2 heterodimer formation and stabilization (By similarity). {ECO:0000250}. |
| O95785 | WIZ | S1352 | ochoa | Protein Wiz (Widely-interspaced zinc finger-containing protein) (Zinc finger protein 803) | May link EHMT1 and EHMT2 histone methyltransferases to the CTBP corepressor machinery. May be involved in EHMT1-EHMT2 heterodimer formation and stabilization (By similarity). {ECO:0000250}. |
| O95810 | CAVIN2 | S169 | ochoa | Caveolae-associated protein 2 (Cavin-2) (PS-p68) (Phosphatidylserine-binding protein) (Serum deprivation-response protein) | Plays an important role in caveolar biogenesis and morphology. Regulates caveolae morphology by inducing membrane curvature within caveolae (PubMed:19525939). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in the lung and fat endothelia but not in the heart endothelia. Negatively regulates the size or stability of CAVIN complexes in the lung endothelial cells. May play a role in targeting PRKCA to caveolae (By similarity). {ECO:0000250|UniProtKB:Q66H98, ECO:0000269|PubMed:19525939}. |
| O95831 | AIFM1 | S249 | ochoa | Apoptosis-inducing factor 1, mitochondrial (EC 1.6.99.-) (Programmed cell death protein 8) | Functions both as NADH oxidoreductase and as regulator of apoptosis (PubMed:17094969, PubMed:20362274, PubMed:23217327, PubMed:33168626). In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway (PubMed:20362274). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (By similarity). The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (PubMed:20362274). Binds to DNA in a sequence-independent manner (PubMed:27178839). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (PubMed:17094969). Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells (PubMed:19418225). In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import (PubMed:26004228). {ECO:0000250|UniProtKB:Q9Z0X1, ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:19418225, ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:33168626}.; FUNCTION: [Isoform 4]: Has NADH oxidoreductase activity. Does not induce nuclear apoptosis. {ECO:0000269|PubMed:16644725}.; FUNCTION: [Isoform 5]: Pro-apoptotic isoform. {ECO:0000269|PubMed:16365034}. |
| O95865 | DDAH2 | S253 | psp | Putative hydrolase DDAH2 (EC 3.-.-.-) (DDAHII) (Inactive N(G),N(G)-dimethylarginine dimethylaminohydrolase 2) (DDAH-2) (Inactive dimethylarginine dimethylaminohydrolase 2) (Protein G6a) (S-phase protein) | Putative hydrolase with unknown substrate (Probable). Does not hydrolyze N(G),N(G)-dimethyl-L-arginine (ADMA) which acts as an inhibitor of NOS (PubMed:21493890, PubMed:37296100). In endothelial cells, induces expression of vascular endothelial growth factor (VEGF) via phosphorylation of the transcription factor SP1 by PKA in a process that is independent of NO and NO synthase (By similarity). Similarly, enhances pancreatic insulin secretion through SP1-mediated transcriptional up-regulation of secretagogin/SCGN, an insulin vesicle docking protein (By similarity). Upon viral infection, relocates to mitochondria where it promotes mitochondrial fission through activation of DNM1L leading to the inhibition of innate response activation mediated by MAVS (PubMed:33850055). {ECO:0000250|UniProtKB:Q99LD8, ECO:0000269|PubMed:21493890, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:37296100, ECO:0000305|PubMed:10493931, ECO:0000305|PubMed:21493890, ECO:0000305|PubMed:37296100}. |
| O95886 | DLGAP3 | S932 | ochoa | Disks large-associated protein 3 (DAP-3) (PSD-95/SAP90-binding protein 3) (SAP90/PSD-95-associated protein 3) (SAPAP3) | May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/SAP90 at the plasma membrane. |
| O96028 | NSD2 | S30 | ochoa | Histone-lysine N-methyltransferase NSD2 (EC 2.1.1.357) (Multiple myeloma SET domain-containing protein) (MMSET) (Nuclear SET domain-containing protein 2) (Protein trithorax-5) (Wolf-Hirschhorn syndrome candidate 1 protein) | Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:19808676, PubMed:22099308, PubMed:27571355, PubMed:29728617, PubMed:33941880). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:22099308). Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (PubMed:22099308). However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells (By similarity). By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes (PubMed:16115125, PubMed:22099308, PubMed:29728617). In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation (By similarity). During heart development, associates with transcription factor NKX2-5 to repress transcription of NKX2-5 target genes (By similarity). Plays an essential role in adipogenesis, by regulating expression of genes involved in pre-adipocyte differentiation (PubMed:29728617). During T-cell receptor (TCR) and CD28-mediated T-cell activation, promotes the transcription of transcription factor BCL6 which is required for follicular helper T (Tfh) cell differentiation (By similarity). During B-cell development, required for the generation of the B1 lineage (By similarity). During B2 cell activation, may contribute to the control of isotype class switch recombination (CRS), splenic germinal center formation, and the humoral immune response (By similarity). Plays a role in class switch recombination of the immunoglobulin heavy chain (IgH) locus during B-cell activation (By similarity). By regulating the methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 recruitment to the IgH switch region and promotes the transcription of IgA (By similarity). {ECO:0000250|UniProtKB:Q8BVE8, ECO:0000269|PubMed:16115125, ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308, ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617, ECO:0000269|PubMed:33941880}.; FUNCTION: [Isoform 1]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). {ECO:0000269|PubMed:22099308}.; FUNCTION: [Isoform 4]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:22099308). Methylation of histone H3 at 'Lys-27' is controversial (PubMed:18172012, PubMed:22099308). Mono-, di- or tri-methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2 and H3K27me3) (PubMed:18172012). Does not methylate histone H3 at 'Lys-27' (PubMed:22099308). May act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment (PubMed:11152655, PubMed:18172012). {ECO:0000269|PubMed:11152655, ECO:0000269|PubMed:18172012, ECO:0000269|PubMed:22099308}. |
| P00338 | LDHA | S69 | ochoa | L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}. |
| P00338 | LDHA | S161 | ochoa|psp | L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}. |
| P00367 | GLUD1 | S370 | psp | Glutamate dehydrogenase 1, mitochondrial (GDH 1) (EC 1.4.1.3) | Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:11254391, PubMed:16023112, PubMed:16959573). Plays a role in insulin homeostasis (PubMed:11297618, PubMed:9571255). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:9571255}. |
| P00387 | CYB5R3 | S82 | ochoa | NADH-cytochrome b5 reductase 3 (B5R) (Cytochrome b5 reductase) (EC 1.6.2.2) (Diaphorase-1) | Catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor. {ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:1400360, ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:2019583, ECO:0000269|PubMed:8119939, ECO:0000269|PubMed:9639531}. |
| P00491 | PNP | S33 | ochoa | Purine nucleoside phosphorylase (PNP) (EC 2.4.2.1) (Inosine phosphorylase) (Inosine-guanosine phosphorylase) | Catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:23438750, PubMed:9305964). Preferentially acts on 6-oxopurine nucleosides including inosine and guanosine (PubMed:9305964). {ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964}. |
| P00558 | PGK1 | S115 | ochoa | Phosphoglycerate kinase 1 (EC 2.7.11.1) (EC 2.7.2.3) (Cell migration-inducing gene 10 protein) (Primer recognition protein 2) (PRP 2) | Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:18463139, ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:30323285, ECO:0000269|PubMed:36849569, ECO:0000269|PubMed:7391028}. |
| P00918 | CA2 | S151 | ochoa | Carbonic anhydrase 2 (EC 4.2.1.1) (Carbonate dehydratase II) (Carbonic anhydrase C) (CAC) (Carbonic anhydrase II) (CA-II) (Cyanamide hydratase CA2) (EC 4.2.1.69) | Catalyzes the reversible hydration of carbon dioxide (PubMed:11327835, PubMed:11802772, PubMed:11831900, PubMed:12056894, PubMed:12171926, PubMed:1336460, PubMed:14736236, PubMed:15300855, PubMed:15453828, PubMed:15667203, PubMed:15865431, PubMed:16106378, PubMed:16214338, PubMed:16290146, PubMed:16686544, PubMed:16759856, PubMed:16807956, PubMed:17127057, PubMed:17251017, PubMed:17314045, PubMed:17330962, PubMed:17346964, PubMed:17540563, PubMed:17588751, PubMed:17705204, PubMed:18024029, PubMed:18162396, PubMed:18266323, PubMed:18374572, PubMed:18481843, PubMed:18618712, PubMed:18640037, PubMed:18942852, PubMed:1909891, PubMed:1910042, PubMed:19170619, PubMed:19186056, PubMed:19206230, PubMed:19520834, PubMed:19778001, PubMed:7761440, PubMed:7901850, PubMed:8218160, PubMed:8262987, PubMed:8399159, PubMed:8451242, PubMed:8485129, PubMed:8639494, PubMed:9265618, PubMed:9398308). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. {ECO:0000269|PubMed:10550681, ECO:0000269|PubMed:11015219, ECO:0000269|PubMed:11327835, ECO:0000269|PubMed:11802772, ECO:0000269|PubMed:11831900, ECO:0000269|PubMed:12056894, ECO:0000269|PubMed:12171926, ECO:0000269|PubMed:1336460, ECO:0000269|PubMed:14736236, ECO:0000269|PubMed:15300855, ECO:0000269|PubMed:15453828, ECO:0000269|PubMed:15667203, ECO:0000269|PubMed:15865431, ECO:0000269|PubMed:15990874, ECO:0000269|PubMed:16106378, ECO:0000269|PubMed:16214338, ECO:0000269|PubMed:16290146, ECO:0000269|PubMed:16686544, ECO:0000269|PubMed:16759856, ECO:0000269|PubMed:16807956, ECO:0000269|PubMed:17127057, ECO:0000269|PubMed:17251017, ECO:0000269|PubMed:17314045, ECO:0000269|PubMed:17330962, ECO:0000269|PubMed:17346964, ECO:0000269|PubMed:17540563, ECO:0000269|PubMed:17588751, ECO:0000269|PubMed:17705204, ECO:0000269|PubMed:18024029, ECO:0000269|PubMed:18162396, ECO:0000269|PubMed:18266323, ECO:0000269|PubMed:18374572, ECO:0000269|PubMed:18481843, ECO:0000269|PubMed:18618712, ECO:0000269|PubMed:18640037, ECO:0000269|PubMed:18942852, ECO:0000269|PubMed:1909891, ECO:0000269|PubMed:1910042, ECO:0000269|PubMed:19170619, ECO:0000269|PubMed:19186056, ECO:0000269|PubMed:19206230, ECO:0000269|PubMed:19520834, ECO:0000269|PubMed:19778001, ECO:0000269|PubMed:7761440, ECO:0000269|PubMed:7901850, ECO:0000269|PubMed:8218160, ECO:0000269|PubMed:8262987, ECO:0000269|PubMed:8399159, ECO:0000269|PubMed:8451242, ECO:0000269|PubMed:8485129, ECO:0000269|PubMed:8639494, ECO:0000269|PubMed:9265618, ECO:0000269|PubMed:9398308}. |
| P01033 | TIMP1 | S178 | ochoa | Metalloproteinase inhibitor 1 (Erythroid-potentiating activity) (EPA) (Fibroblast collagenase inhibitor) (Collagenase inhibitor) (Tissue inhibitor of metalloproteinases 1) (TIMP-1) | Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. {ECO:0000269|PubMed:1420137, ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:17050530, ECO:0000269|PubMed:1730286, ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517, ECO:0000269|PubMed:8541540, ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:9065415}. |
| P01130 | LDLR | S820 | ochoa | Low-density lipoprotein receptor (LDL receptor) | Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization (PubMed:30443021). {ECO:0000269|PubMed:3005267, ECO:0000269|PubMed:30443021, ECO:0000269|PubMed:6091915}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. {ECO:0000269|PubMed:10535997, ECO:0000269|PubMed:12615904}.; FUNCTION: (Microbial infection) Acts as a receptor for Vesicular stomatitis virus. {ECO:0000269|PubMed:23589850}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. {ECO:0000269|PubMed:11100124}.; FUNCTION: (Microbial infection) Acts as a receptor for Crimean-Congo hemorrhagic fever virus (CCHFV). {ECO:0000269|PubMed:38182887}.; FUNCTION: (Microbial infection) Acts as a receptor for many Alphavirus, including Getah virus (GETV), Ross river virus (RRV) and Semliki Forest virus. {ECO:0000269|PubMed:38245515}. |
| P02008 | HBZ | S53 | ochoa | Hemoglobin subunit zeta (HBAZ) (Hemoglobin zeta chain) (Zeta-globin) | The zeta chain is an alpha-type chain of mammalian embryonic hemoglobin. |
| P02042 | HBD | S87 | ochoa | Hemoglobin subunit delta (Delta-globin) (Hemoglobin delta chain) | Involved in oxygen transport from the lung to the various peripheral tissues. |
| P02545 | LMNA | S568 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02686 | MBP | S174 | ochoa | Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) | The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}. |
| P02686 | MBP | S205 | ochoa | Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) | The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}. |
| P03372 | ESR1 | S282 | psp | Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) | Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [Isoform 3]: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}. |
| P04792 | HSPB1 | S49 | ochoa | Heat shock protein beta-1 (HspB1) (28 kDa heat shock protein) (Estrogen-regulated 24 kDa protein) (Heat shock 27 kDa protein) (HSP 27) (Heat shock protein family B member 1) (Stress-responsive protein 27) (SRP27) | Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state (PubMed:10383393, PubMed:20178975). Plays a role in stress resistance and actin organization (PubMed:19166925). Through its molecular chaperone activity may regulate numerous biological processes including the phosphorylation and the axonal transport of neurofilament proteins (PubMed:23728742). {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:20178975, ECO:0000269|PubMed:23728742}. |
| P05023 | ATP1A1 | S369 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P05067 | APP | S697 | psp | Amyloid-beta precursor protein (APP) (ABPP) (APPI) (Alzheimer disease amyloid A4 protein homolog) (Alzheimer disease amyloid protein) (Amyloid precursor protein) (Amyloid-beta (A4) precursor protein) (Amyloid-beta A4 protein) (Cerebral vascular amyloid peptide) (CVAP) (PreA4) (Protease nexin-II) (PN-II) [Cleaved into: N-APP; Soluble APP-alpha (S-APP-alpha); Soluble APP-beta (S-APP-beta); C99 (Beta-secretase C-terminal fragment) (Beta-CTF); Amyloid-beta protein 42 (Abeta42) (Beta-APP42); Amyloid-beta protein 40 (Abeta40) (Beta-APP40); C83 (Alpha-secretase C-terminal fragment) (Alpha-CTF); P3(42); P3(40); C80; Gamma-secretase C-terminal fragment 59 (Amyloid intracellular domain 59) (AICD-59) (AID(59)) (Gamma-CTF(59)); Gamma-secretase C-terminal fragment 57 (Amyloid intracellular domain 57) (AICD-57) (AID(57)) (Gamma-CTF(57)); Gamma-secretase C-terminal fragment 50 (Amyloid intracellular domain 50) (AICD-50) (AID(50)) (Gamma-CTF(50)); C31] | Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. {ECO:0000250, ECO:0000250|UniProtKB:P12023, ECO:0000269|PubMed:17062754, ECO:0000269|PubMed:23011729, ECO:0000269|PubMed:25122912}.; FUNCTION: Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.; FUNCTION: [Amyloid-beta protein 42]: More effective reductant than amyloid-beta protein 40. May activate mononuclear phagocytes in the brain and elicit inflammatory responses.; FUNCTION: Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain. {ECO:0000250}.; FUNCTION: The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. |
| P05121 | SERPINE1 | S218 | ochoa | Plasminogen activator inhibitor 1 (PAI) (PAI-1) (Endothelial plasminogen activator inhibitor) (Serpin E1) | Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:17912461, PubMed:8481516, PubMed:9207454, PubMed:21925150). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084). {ECO:0000250|UniProtKB:P22777, ECO:0000269|PubMed:15001579, ECO:0000269|PubMed:15853774, ECO:0000269|PubMed:16862142, ECO:0000269|PubMed:17912461, ECO:0000269|PubMed:18386027, ECO:0000269|PubMed:21925150, ECO:0000269|PubMed:25808697, ECO:0000269|PubMed:27046084, ECO:0000269|PubMed:8481516, ECO:0000269|PubMed:9168821, ECO:0000269|PubMed:9175705, ECO:0000269|PubMed:9207454}. |
| P05181 | CYP2E1 | S74 | psp | Cytochrome P450 2E1 (EC 1.14.14.1) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) | A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}. |
| P05230 | FGF1 | S131 | psp | Fibroblast growth factor 1 (FGF-1) (Acidic fibroblast growth factor) (aFGF) (Endothelial cell growth factor) (ECGF) (Heparin-binding growth factor 1) (HBGF-1) | Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as a potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107). {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:20145243, ECO:0000269|PubMed:20422052, ECO:0000269|PubMed:23469107, ECO:0000269|PubMed:8663044}. |
| P05413 | FABP3 | S35 | ochoa | Fatty acid-binding protein, heart (Fatty acid-binding protein 3) (Heart-type fatty acid-binding protein) (H-FABP) (Mammary-derived growth inhibitor) (MDGI) (Muscle fatty acid-binding protein) (M-FABP) | FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. |
| P05455 | SSB | S153 | ochoa | Lupus La protein (La autoantigen) (La ribonucleoprotein) (Sjoegren syndrome type B antigen) (SS-B) | Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation (PubMed:2470590, PubMed:3192525). In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12384597). {ECO:0000269|PubMed:12384597, ECO:0000269|PubMed:2470590, ECO:0000269|PubMed:3192525}. |
| P06239 | LCK | S150 | ochoa | Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) | Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}. |
| P06576 | ATP5F1B | S106 | ochoa | ATP synthase F(1) complex subunit beta, mitochondrial (EC 7.1.2.2) (ATP synthase F1 subunit beta) | Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable) (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain (PubMed:37244256). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:25168243, ECO:0000305|PubMed:36239646, ECO:0000305|PubMed:37244256}. |
| P06732 | CKM | S332 | ochoa | Creatine kinase M-type (EC 2.7.3.2) (Creatine kinase M chain) (Creatine phosphokinase M-type) (CPK-M) (M-CK) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. {ECO:0000250|UniProtKB:P00563}. |
| P06733 | ENO1 | S141 | ochoa | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P06733 | ENO1 | S157 | ochoa | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P06733 | ENO1 | S370 | ochoa | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P06744 | GPI | S176 | ochoa | Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) (Autocrine motility factor) (AMF) (Neuroleukin) (NLK) (Phosphoglucose isomerase) (PGI) (Phosphohexose isomerase) (PHI) (Sperm antigen 36) (SA-36) | In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:28803808). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility (PubMed:11437381). Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons (PubMed:11004567, PubMed:3352745). It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (PubMed:11004567, PubMed:3352745). {ECO:0000269|PubMed:11004567, ECO:0000269|PubMed:11437381, ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:3352745}. |
| P06744 | GPI | S532 | ochoa | Glucose-6-phosphate isomerase (GPI) (EC 5.3.1.9) (Autocrine motility factor) (AMF) (Neuroleukin) (NLK) (Phosphoglucose isomerase) (PGI) (Phosphohexose isomerase) (PHI) (Sperm antigen 36) (SA-36) | In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:28803808). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility (PubMed:11437381). Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons (PubMed:11004567, PubMed:3352745). It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (PubMed:11004567, PubMed:3352745). {ECO:0000269|PubMed:11004567, ECO:0000269|PubMed:11437381, ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:3352745}. |
| P06748 | NPM1 | S149 | ochoa | Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) | Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}. |
| P07195 | LDHB | S162 | ochoa|psp | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| P07195 | LDHB | S303 | ochoa | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| P07203 | GPX1 | S34 | ochoa | Glutathione peroxidase 1 (GPx-1) (GSHPx-1) (EC 1.11.1.9) (Cellular glutathione peroxidase) (Phospholipid-hydroperoxide glutathione peroxidase GPX1) (EC 1.11.1.12) | Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). In platelets catalyzes the reduction of 12-hydroperoxyeicosatetraenoic acid, the primary product of the arachidonate 12-lipoxygenase pathway (PubMed:11115402). {ECO:0000269|PubMed:11115402, ECO:0000269|PubMed:36608588}. |
| P07305 | H1-0 | S92 | ochoa | Histone H1.0 (Histone H1') (Histone H1(0)) [Cleaved into: Histone H1.0, N-terminally processed] | Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. The histones H1.0 are found in cells that are in terminal stages of differentiation or that have low rates of cell division. |
| P07355 | ANXA2 | S26 | ochoa|psp | Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity). {ECO:0000250|UniProtKB:P07356, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.; FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen. {ECO:0000269|PubMed:25139904}. |
| P07355 | ANXA2 | S184 | ochoa | Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity). {ECO:0000250|UniProtKB:P07356, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.; FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen. {ECO:0000269|PubMed:25139904}. |
| P07864 | LDHC | S161 | ochoa | L-lactate dehydrogenase C chain (LDH-C) (EC 1.1.1.27) (Cancer/testis antigen 32) (CT32) (LDH testis subunit) (LDH-X) | Possible role in sperm motility. |
| P07949 | RET | S829 | ochoa | Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment] | Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698). {ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:25242331, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31118272}.; FUNCTION: [Isoform 1]: Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. {ECO:0000269|PubMed:28846099}. |
| P07996 | THBS1 | S627 | ochoa | Thrombospondin-1 (Glycoprotein G) | Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions (PubMed:15014436, PubMed:18285447, PubMed:2430973, PubMed:6489349). Multifunctional, involved in inflammation, angiogenesis, wound healing, reactive oxygen species (ROS) signaling, nitrous oxide (NO) signaling, apoptosis, senescence, aging, cellular self-renewal, stemness, and cardiovascular and metabolic homeostasis (PubMed:10613822, PubMed:11134179, PubMed:1371676, PubMed:14568985, PubMed:24511121, PubMed:29042481, PubMed:32679764). Negatively modulates dendritic cell activation and cytokine release, as part of an autocrine feedback loop, contributing to the resolution of inflammation and immune homeostasis (PubMed:14568985). Ligand for receptor CD47 (PubMed:19004835, PubMed:8550562). Modulates nitrous oxide (NO) signaling via CD47, hence playing a role as a pressor agent, supporting blood pressure (By similarity). Plays a role in endothelial cell senescence, acting via CD47, by increasing the abundance and activation of NADPH oxidase NOX1, and so generating excess ROS (PubMed:29042481). Inhibits stem cell self-renewal, acting via CD47 signaling, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 (By similarity). Negatively modulates wound healing, acting via CD47 (By similarity). Ligand for receptor CD36 (PubMed:10613822, PubMed:11134179, PubMed:1371676). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting via CD36 (By similarity). Plays a role in suppressing angiogenesis, acting, depending on context, via CD36 or CD47 (PubMed:10613822, PubMed:11134179, PubMed:1371676, PubMed:32679764). Promotes cellular senescence in a TP53-CDKN1A-RB1 signaling-dependent manner (PubMed:29042481). Ligand for immunoglobulin-like cell surface receptor SIRPA (PubMed:24511121). Involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production, acting via interaction with SIRPA (PubMed:24511121). Plays a role in metabolic dysfunction in diet-induced obesity, perhaps acting by exacerbating adipose inflammatory activity; its effects may be mediated, at least in part, through enhanced adipocyte proliferation (By similarity). Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors (By similarity). May be involved in age-related conditions, including metabolic dysregulation, during normal aging (PubMed:29042481, PubMed:32679764). {ECO:0000250|UniProtKB:P35441, ECO:0000269|PubMed:10613822, ECO:0000269|PubMed:11134179, ECO:0000269|PubMed:1371676, ECO:0000269|PubMed:14568985, ECO:0000269|PubMed:15014436, ECO:0000269|PubMed:18285447, ECO:0000269|PubMed:19004835, ECO:0000269|PubMed:2430973, ECO:0000269|PubMed:24511121, ECO:0000269|PubMed:29042481, ECO:0000269|PubMed:32679764, ECO:0000269|PubMed:6489349, ECO:0000269|PubMed:8550562}. |
| P08047 | SP1 | S379 | ochoa | Transcription factor Sp1 | Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}. |
| P08138 | NGFR | S354 | ochoa | Tumor necrosis factor receptor superfamily member 16 (Gp80-LNGFR) (Low affinity neurotrophin receptor p75NTR) (Low-affinity nerve growth factor receptor) (NGF receptor) (Low-affinity nerve growth factor receptor p75NGFR) (Low-affinity nerve growth factor receptor p75NGR) (p75 ICD) (CD antigen CD271) | Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4. Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF (PubMed:24908487). Plays an important role in differentiation and survival of specific neuronal populations during development (By similarity). Can mediate cell survival as well as cell death of neural cells. Plays a role in the inactivation of RHOA (PubMed:26646181). Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Necessary for the circadian oscillation of the clock genes BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCmgetaN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver (PubMed:23785138). Together with BFAR negatively regulates NF-kappa-B and JNK-related signaling pathways (PubMed:22566094). {ECO:0000250, ECO:0000250|UniProtKB:Q9Z0W1, ECO:0000269|PubMed:14966521, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:3022937}. |
| P08195 | SLC3A2 | S410 | psp | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| P08195 | SLC3A2 | S607 | ochoa | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| P08237 | PFKM | S398 | ochoa | ATP-dependent 6-phosphofructokinase, muscle type (ATP-PFK) (PFK-M) (EC 2.7.1.11) (6-phosphofructokinase type A) (Phosphofructo-1-kinase isozyme A) (PFK-A) (Phosphohexokinase) | Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis. |
| P08240 | SRPRA | S286 | ochoa | Signal recognition particle receptor subunit alpha (SR-alpha) (Docking protein alpha) (DP-alpha) | Component of the signal recognition particle (SRP) complex receptor (SR) (PubMed:16439358). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (PubMed:16675701, PubMed:34020957). Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SRP subunit SRP54 (PubMed:34020957). SRP receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (PubMed:34020957). {ECO:0000269|PubMed:16439358, ECO:0000269|PubMed:16675701, ECO:0000269|PubMed:34020957}. |
| P08319 | ADH4 | S278 | ochoa | All-trans-retinol dehydrogenase [NAD(+)] ADH4 (EC 1.1.1.105) (Alcohol dehydrogenase 2) (Alcohol dehydrogenase 4) (Alcohol dehydrogenase class II pi chain) | Catalyzes the NAD-dependent oxidation of either all-trans-retinol or 9-cis-retinol (PubMed:17279314). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Also catalyzes the reduction of benzoquinones (PubMed:10514444). {ECO:0000269|PubMed:10514444, ECO:0000269|PubMed:16081420, ECO:0000269|PubMed:17279314}. |
| P08581 | MET | S966 | ochoa | Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}. |
| P08631 | HCK | S214 | ochoa | Tyrosine-protein kinase HCK (EC 2.7.10.2) (Hematopoietic cell kinase) (Hemopoietic cell kinase) (p59-HCK/p60-HCK) (p59Hck) (p61Hck) | Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790, ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024, ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982, ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996, ECO:0000269|PubMed:9407116}. |
| P08651 | NFIC | S427 | ochoa | Nuclear factor 1 C-type (NF1-C) (Nuclear factor 1/C) (CCAAT-box-binding transcription factor) (CTF) (Nuclear factor I/C) (NF-I/C) (NFI-C) (TGGCA-binding protein) | Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication. |
| P08670 | VIM | S214 | ochoa | Vimentin | Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally. Plays a role in cell directional movement, orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Protects SCRIB from proteasomal degradation and facilitates its localization to intermediate filaments in a cell contact-mediated manner (By similarity). {ECO:0000250|UniProtKB:A0A8C0N8E3, ECO:0000250|UniProtKB:P31000}.; FUNCTION: Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. {ECO:0000269|PubMed:21746880}. |
| P08708 | RPS17 | S113 | ochoa | Small ribosomal subunit protein eS17 (40S ribosomal protein S17) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P09327 | VIL1 | S366 | ochoa | Villin-1 | Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. {ECO:0000269|PubMed:11500485, ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600, ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613, ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174, ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}. |
| P09467 | FBP1 | S88 | psp | Fructose-1,6-bisphosphatase 1 (FBPase 1) (EC 3.1.3.11) (D-fructose-1,6-bisphosphate 1-phosphohydrolase 1) (Liver FBPase) | Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000269|PubMed:16497803, ECO:0000269|PubMed:18375435, ECO:0000269|PubMed:22517657}. |
| P09467 | FBP1 | S170 | psp | Fructose-1,6-bisphosphatase 1 (FBPase 1) (EC 3.1.3.11) (D-fructose-1,6-bisphosphate 1-phosphohydrolase 1) (Liver FBPase) | Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000269|PubMed:16497803, ECO:0000269|PubMed:18375435, ECO:0000269|PubMed:22517657}. |
| P09471 | GNAO1 | S47 | ochoa | Guanine nucleotide-binding protein G(o) subunit alpha (EC 3.6.5.-) | Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:29925951, PubMed:33408414). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (By similarity). Signaling by an activated GPCR promotes GDP release and GTP binding (By similarity). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (By similarity). Signaling is mediated via effector proteins, such as adenylate cyclase (By similarity). Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). {ECO:0000250|UniProtKB:P18872, ECO:0000269|PubMed:29925951, ECO:0000269|PubMed:33408414}. |
| P0C1Z6 | TFPT | S145 | ochoa | TCF3 fusion partner (INO80 complex subunit F) (Protein FB1) | Appears to promote apoptosis in a p53/TP53-independent manner.; FUNCTION: Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. |
| P0C7M8 | CLEC2L | S55 | ochoa | C-type lectin domain family 2 member L | None |
| P0C7U0 | ELFN1 | S461 | ochoa | Protein ELFN1 (Extracellular leucine-rich repeat and fibronectin type-III domain-containing protein 1) (Protein phosphatase 1 regulatory subunit 28) | Postsynaptic protein that regulates circuit dynamics in the central nervous system by modulating the temporal dynamics of interneuron recruitment. Specifically present in excitatory synapses onto oriens-lacunosum molecular (OLM) interneurons and acts as a regulator of presynaptic release probability to direct the formation of highly facilitating pyramidal-OLM synapses (By similarity). Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000250, ECO:0000269|PubMed:19389623}. |
| P0DMV8 | HSPA1A | S340 | ochoa | Heat shock 70 kDa protein 1A (Heat shock 70 kDa protein 1) (HSP70-1) (HSP70.1) (Heat shock protein family A member 1A) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:24318877, PubMed:26865365). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). Required as a co-chaperone for optimal STUB1/CHIP ubiquitination of NFATC3 (By similarity). Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). Involved in the clearance of misfolded PRDM1/Blimp-1 proteins. Sequesters them in the cytoplasm and promotes their association with SYNV1/HRD1, leading to proteasomal degradation (PubMed:28842558). {ECO:0000250|UniProtKB:P0DMW0, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:28842558, ECO:0000269|PubMed:9499401, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}. |
| P0DMV9 | HSPA1B | S340 | ochoa | Heat shock 70 kDa protein 1B (Heat shock 70 kDa protein 2) (HSP70-2) (HSP70.2) (Heat shock protein family A member 1B) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:24318877, PubMed:26865365). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.; FUNCTION: (Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. {ECO:0000269|PubMed:16537599}. |
| P0DPH7 | TUBA3C | S379 | ochoa | Tubulin alpha-3C chain (EC 3.6.5.-) (Alpha-tubulin 2) (Alpha-tubulin 3C) (Tubulin alpha-2 chain) [Cleaved into: Detyrosinated tubulin alpha-3C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH8 | TUBA3D | S379 | ochoa | Tubulin alpha-3D chain (EC 3.6.5.-) (Alpha-tubulin 3D) [Cleaved into: Detyrosinated tubulin alpha-3D chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P10275 | AR | S293 | psp | Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4) | Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:25091737}.; FUNCTION: [Isoform 3]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}.; FUNCTION: [Isoform 4]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}. |
| P10275 | AR | S579 | psp | Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4) | Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:25091737}.; FUNCTION: [Isoform 3]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}.; FUNCTION: [Isoform 4]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}. |
| P10412 | H1-4 | S104 | ochoa | Histone H1.4 (Histone H1b) (Histone H1s-4) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P10636 | MAPT | S61 | ochoa | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| P10636 | MAPT | S673 | ochoa|psp | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| P10644 | PRKAR1A | S238 | ochoa | cAMP-dependent protein kinase type I-alpha regulatory subunit (Tissue-specific extinguisher 1) (TSE1) | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:26405036}. |
| P10768 | ESD | S214 | ochoa | S-formylglutathione hydrolase (FGH) (EC 3.1.2.12) (Esterase D) (Methylumbelliferyl-acetate deacetylase) (EC 3.1.1.56) | Serine hydrolase involved in the detoxification of formaldehyde. {ECO:0000269|PubMed:3770744, ECO:0000269|PubMed:4768551}. |
| P11137 | MAP2 | S738 | ochoa | Microtubule-associated protein 2 (MAP-2) | The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules. |
| P11137 | MAP2 | S1679 | psp | Microtubule-associated protein 2 (MAP-2) | The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules. |
| P11137 | MAP2 | S1710 | psp | Microtubule-associated protein 2 (MAP-2) | The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules. |
| P11142 | HSPA8 | S221 | ochoa | Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Heat shock protein family A member 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity). {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. |
| P11233 | RALA | S22 | ochoa | Ras-related protein Ral-A (EC 3.6.5.2) | Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors (PubMed:18756269, PubMed:19306925, PubMed:20005108, PubMed:21822277, PubMed:30500825). Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling (PubMed:20005108). Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells (PubMed:19306925). During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody (PubMed:18756269). During mitosis, also controls mitochondrial fission by recruiting to the mitochondrion RALBP1, which mediates the phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-CDK1 (PubMed:21822277). {ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:20005108, ECO:0000269|PubMed:21822277, ECO:0000269|PubMed:30500825}. |
| P11234 | RALB | S22 | ochoa | Ras-related protein Ral-B (EC 3.6.5.2) | Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking (PubMed:10393179, PubMed:17875936, PubMed:18756269). Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles (By similarity). Required both to stabilize the assembly of the exocyst complex and to localize functional exocyst complexes to the leading edge of migrating cells (By similarity). Required for suppression of apoptosis (PubMed:17875936). In late stages of cytokinesis, upon completion of the bridge formation between dividing cells, mediates exocyst recruitment to the midbody to drive abscission (PubMed:18756269). Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors (PubMed:10393179). {ECO:0000250|UniProtKB:P36860, ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:17875936, ECO:0000269|PubMed:18756269}. |
| P11274 | BCR | S205 | ochoa | Breakpoint cluster region protein (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-26) | Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. |
| P11413 | G6PD | S132 | ochoa | Glucose-6-phosphate 1-dehydrogenase (G6PD) (EC 1.1.1.49) | Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:35122041, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:743300}. |
| P12270 | TPR | S1459 | ochoa | Nucleoprotein TPR (Megator) (NPC-associated intranuclear protein) (Translocated promoter region protein) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:11952838, PubMed:22253824). Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:9864356}. |
| P12814 | ACTN1 | S356 | ochoa | Alpha-actinin-1 (Alpha-actinin cytoskeletal isoform) (F-actin cross-linking protein) (Non-muscle alpha-actinin-1) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000269|PubMed:22689882}. |
| P13010 | XRCC5 | S102 | ochoa | X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}. |
| P13010 | XRCC5 | S175 | ochoa | X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}. |
| P13010 | XRCC5 | S255 | ochoa | X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}. |
| P13056 | NR2C1 | S52 | ochoa | Nuclear receptor subfamily 2 group C member 1 (Orphan nuclear receptor TR2) (Testicular receptor 2) | Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation. {ECO:0000269|PubMed:12093804, ECO:0000269|PubMed:17010934}. |
| P13569 | CFTR | S1045 | psp | Cystic fibrosis transmembrane conductance regulator (CFTR) (ATP-binding cassette sub-family C member 7) (Channel conductance-controlling ATPase) (EC 5.6.1.6) (cAMP-dependent chloride channel) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:12727866, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:29393851, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}. |
| P13637 | ATP1A3 | S359 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-3 (Na(+)/K(+) ATPase alpha-3 subunit) (EC 7.2.2.13) (Na(+)/K(+) ATPase alpha(III) subunit) (Sodium pump subunit alpha-3) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P13807 | GYS1 | S412 | ochoa | Glycogen [starch] synthase, muscle (EC 2.4.1.11) (Glycogen synthase 1) | Glycogen synthase participates in the glycogen biosynthetic process along with glycogenin and glycogen branching enzyme. Extends the primer composed of a few glucose units formed by glycogenin by adding new glucose units to it. In this context, glycogen synthase transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan. {ECO:0000269|PubMed:35835870}. |
| P13929 | ENO3 | S370 | ochoa | Beta-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 3) (Muscle-specific enolase) (MSE) (Skeletal muscle enolase) | Glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Appears to have a function in striated muscle development and regeneration. {ECO:0000250|UniProtKB:P15429}. |
| P14618 | PKM | S127 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P14618 | PKM | S222 | ochoa|psp | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P14618 | PKM | S346 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P14625 | HSP90B1 | S42 | ochoa | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P14625 | HSP90B1 | S403 | ochoa | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P15056 | BRAF | S394 | ochoa|psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P15056 | BRAF | S467 | psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P15822 | HIVEP1 | S670 | ochoa | Zinc finger protein 40 (Cirhin interaction protein) (CIRIP) (Gate keeper of apoptosis-activating protein) (GAAP) (Human immunodeficiency virus type I enhancer-binding protein 1) (HIV-EP1) (Major histocompatibility complex-binding protein 1) (MBP-1) (Positive regulatory domain II-binding factor 1) (PRDII-BF1) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV-1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, and interferon-beta genes. It may act in T-cell activation. Involved in activating HIV-1 gene expression. Isoform 2 and isoform 3 also bind to the IPCS (IRF1 and p53 common sequence) DNA sequence in the promoter region of interferon regulatory factor 1 and p53 genes and are involved in transcription regulation of these genes. Isoform 2 does not activate HIV-1 gene expression. Isoform 2 and isoform 3 may be involved in apoptosis. |
| P15923 | TCF3 | S328 | ochoa | Transcription factor E2-alpha (Class B basic helix-loop-helix protein 21) (bHLHb21) (Immunoglobulin enhancer-binding factor E12/E47) (Immunoglobulin transcription factor 1) (Kappa-E2-binding factor) (Transcription factor 3) (TCF-3) (Transcription factor ITF-1) | Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition (By similarity). Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation (By similarity). Together with TCF15, required for the mesenchymal to epithelial transition (By similarity). Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (By similarity). {ECO:0000250|UniProtKB:P15806, ECO:0000269|PubMed:2493990}.; FUNCTION: [Isoform E47]: Facilitates ATOH7 binding to DNA at the consensus sequence 5'-CAGGTG-3', and positively regulates transcriptional activity. {ECO:0000269|PubMed:31696227}. |
| P15924 | DSP | S2526 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P15924 | DSP | S2575 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P16066 | NPR1 | S542 | psp | Atrial natriuretic peptide receptor 1 (EC 4.6.1.2) (Atrial natriuretic peptide receptor type A) (ANP-A) (ANPR-A) (NPR-A) (Guanylate cyclase A) (GC-A) | Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis (PubMed:39543315). Plays an essential role in the regulation of endothelial cell senescence and vascular aging (PubMed:36016499). Upon activation by ANP or BNP, stimulates the production of cyclic guanosine monophosphate (cGMP) that promotes vascular tone and volume homeostasis by activation of protein kinase cGMP-dependent 1/PRKG1 and subsequently PRKAA1, thereby controlling blood pressure and maintaining cardiovascular homeostasis (PubMed:36016499). {ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:36016499, ECO:0000269|PubMed:39543315}. |
| P16144 | ITGB4 | S1454 | ochoa | Integrin beta-4 (GP150) (CD antigen CD104) | Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}. |
| P16144 | ITGB4 | S1747 | ochoa | Integrin beta-4 (GP150) (CD antigen CD104) | Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}. |
| P16157 | ANK1 | S1617 | ochoa | Ankyrin-1 (ANK-1) (Ankyrin-R) (Erythrocyte ankyrin) | Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. {ECO:0000269|PubMed:12456646, ECO:0000269|PubMed:35835865}.; FUNCTION: [Isoform Mu17]: Together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils. {ECO:0000269|PubMed:12527750}. |
| P16401 | H1-5 | S107 | ochoa | Histone H1.5 (Histone H1a) (Histone H1b) (Histone H1s-3) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P16402 | H1-3 | S105 | ochoa | Histone H1.3 (Histone H1c) (Histone H1s-2) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P16403 | H1-2 | S104 | ochoa | Histone H1.2 (Histone H1c) (Histone H1d) (Histone H1s-1) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| P16871 | IL7R | S297 | ochoa | Interleukin-7 receptor subunit alpha (IL-7 receptor subunit alpha) (IL-7R subunit alpha) (IL-7R-alpha) (IL-7RA) (CDw127) (CD antigen CD127) | Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP). |
| P17028 | ZNF24 | S39 | ochoa | Zinc finger protein 24 (Retinoic acid suppression protein A) (RSG-A) (Zinc finger and SCAN domain-containing protein 3) (Zinc finger protein 191) (Zinc finger protein KOX17) | Transcription factor required for myelination of differentiated oligodendrocytes. Required for the conversion of oligodendrocytes from the premyelinating to the myelinating state. In the developing central nervous system (CNS), involved in the maintenance in the progenitor stage by promoting the cell cycle. Specifically binds to the 5'-TCAT-3' DNA sequence (By similarity). Has transcription repressor activity in vitro. {ECO:0000250, ECO:0000269|PubMed:10585455}. |
| P17302 | GJA1 | S262 | ochoa|psp | Gap junction alpha-1 protein (Connexin-43) (Cx43) (Gap junction 43 kDa heart protein) | Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity). {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P23242}. |
| P17302 | GJA1 | S325 | ochoa|psp | Gap junction alpha-1 protein (Connexin-43) (Cx43) (Gap junction 43 kDa heart protein) | Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity). {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P23242}. |
| P17600 | SYN1 | S341 | ochoa | Synapsin-1 (Brain protein 4.1) (Synapsin I) | Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (PubMed:21441247, PubMed:23406870). Also involved in the regulation of axon outgrowth and synaptogenesis (By similarity). The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level (By similarity). {ECO:0000250|UniProtKB:O88935, ECO:0000250|UniProtKB:P09951, ECO:0000269|PubMed:21441247, ECO:0000269|PubMed:23406870}. |
| P17612 | PRKACA | S54 | ochoa | cAMP-dependent protein kinase catalytic subunit alpha (PKA C-alpha) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:31112131). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (PubMed:33934390). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:33934390}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}. |
| P17655 | CAPN2 | S369 | psp | Calpain-2 catalytic subunit (EC 3.4.22.53) (Calcium-activated neutral proteinase 2) (CANP 2) (Calpain M-type) (Calpain large polypeptide L2) (Calpain-2 large subunit) (Millimolar-calpain) (M-calpain) | Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' (PubMed:17650508). Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs (By similarity). {ECO:0000250|UniProtKB:O08529, ECO:0000269|PubMed:17650508}. |
| P17661 | DES | S68 | ochoa | Desmin | Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Required for nuclear membrane integrity, via anchoring at the cell tip and nuclear envelope, resulting in maintenance of microtubule-derived intracellular mechanical forces (By similarity). Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity). {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190, ECO:0000303|PubMed:25358400}. |
| P17677 | GAP43 | S96 | ochoa | Neuromodulin (Axonal membrane protein GAP-43) (Growth-associated protein 43) (Neural phosphoprotein B-50) (pp46) | This protein is associated with nerve growth. It is a major component of the motile 'growth cones' that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction. {ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:21152083}. |
| P17858 | PFKL | S398 | ochoa | ATP-dependent 6-phosphofructokinase, liver type (ATP-PFK) (PFK-L) (EC 2.7.1.11) (6-phosphofructokinase type B) (Phosphofructo-1-kinase isozyme B) (PFK-B) (Phosphohexokinase) | Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (By similarity). {ECO:0000250|UniProtKB:P12382, ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}. |
| P18031 | PTPN1 | S70 | ochoa | Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) | Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}. |
| P18031 | PTPN1 | S203 | ochoa | Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) | Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}. |
| P18031 | PTPN1 | S243 | psp | Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) | Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}. |
| P18146 | EGR1 | S301 | psp | Early growth response protein 1 (EGR-1) (AT225) (Nerve growth factor-induced protein A) (NGFI-A) (Transcription factor ETR103) (Transcription factor Zif268) (Zinc finger protein 225) (Zinc finger protein Krox-24) | Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, PubMed:25999311). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (By similarity). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (By similarity). {ECO:0000250|UniProtKB:P08046, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:25999311}. |
| P18206 | VCL | S443 | ochoa | Vinculin (Metavinculin) (MV) | Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}. |
| P18583 | SON | S1631 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P18583 | SON | S1670 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P18583 | SON | S2357 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P18827 | SDC1 | S285 | ochoa | Syndecan-1 (SYND1) (CD antigen CD138) | Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (By similarity). Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413). Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (By similarity). {ECO:0000250|UniProtKB:P18828, ECO:0000269|PubMed:22660413}. |
| P18887 | XRCC1 | S371 | psp | DNA repair protein XRCC1 (X-ray repair cross-complementing protein 1) | Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes (PubMed:11163244, PubMed:28002403). Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity (PubMed:28002403, PubMed:34102106, PubMed:34811483). Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity (PubMed:14500814, PubMed:34102106, PubMed:34811483). {ECO:0000269|PubMed:11163244, ECO:0000269|PubMed:14500814, ECO:0000269|PubMed:28002403, ECO:0000269|PubMed:34102106, ECO:0000269|PubMed:34811483}. |
| P19021 | PAM | S918 | ochoa | Peptidyl-glycine alpha-amidating monooxygenase (PAM) [Includes: Peptidylglycine alpha-hydroxylating monooxygenase (PHM) (EC 1.14.17.3); Peptidyl-alpha-hydroxyglycine alpha-amidating lyase (EC 4.3.2.5) (Peptidylamidoglycolate lyase) (PAL)] | Bifunctional enzyme that catalyzes amidation of the C-terminus of proteins (PubMed:12699694, PubMed:2357221). Alpha-amidation is present at the C-terminus of many endocrine hormones and neuropeptides and is required for their activity (PubMed:1575450). C-terminal amidation also takes place in response to protein fragmentation triggered by oxidative stress, promoting degradation of amidated protein fragments by the proteasome (PubMed:2207077). Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme (PubMed:12699694). The first step, catalyzed by peptidyl alpha-hydroxylating monooxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate (PubMed:12699694). The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (PubMed:12699694). Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (By similarity). {ECO:0000250|UniProtKB:P14925, ECO:0000269|PubMed:12699694, ECO:0000269|PubMed:2357221, ECO:0000303|PubMed:1575450, ECO:0000303|PubMed:2207077}. |
| P19484 | TFEB | S81 | ochoa | Transcription factor EB (Class E basic helix-loop-helix protein 35) (bHLHe35) | Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:30120233, PubMed:31672913, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823, PubMed:36749723, PubMed:37079666). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (PubMed:19556463, PubMed:22692423). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica: infection promotes itaconate production, leading to alkylation, resulting in nuclear localization and transcription factor activity (PubMed:35662396). Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response (PubMed:35662396). In association with ACSS2, promotes the expression of genes involved in lysosome biogenesis and both autophagy upon glucose deprivation (PubMed:28552616). {ECO:0000250|UniProtKB:Q9R210, ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:36749723, ECO:0000269|PubMed:37079666}. |
| P19525 | EIF2AK2 | S97 | ochoa|psp | Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) | IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. |
| P20290 | BTF3 | S173 | ochoa | Transcription factor BTF3 (Nascent polypeptide-associated complex subunit beta) (NAC-beta) (RNA polymerase B transcription factor 3) | When associated with NACA, prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. BTF3 is also a general transcription factor that can form a stable complex with RNA polymerase II. Required for the initiation of transcription. {ECO:0000269|PubMed:10982809}. |
| P20648 | ATP4A | S228 | ochoa | Potassium-transporting ATPase alpha chain 1 (EC 7.2.2.19) (Gastric H(+)/K(+) ATPase subunit alpha) (Proton pump) | The catalytic subunit of the gastric H(+)/K(+) ATPase pump which transports H(+) ions in exchange for K(+) ions across the apical membrane of parietal cells. Uses ATP as an energy source to pump H(+) ions to the gastric lumen while transporting K(+) ion from the lumen into the cell (By similarity). Remarkably generates a million-fold proton gradient across the gastric parietal cell membrane, acidifying the gastric juice down to pH 1 (By similarity). Within a transport cycle, the transfer of a H(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing (E1) to outward-facing state (E2). The release of the H(+) ion in the stomach lumen is followed by binding of K(+) ion converting the pump conformation back to the E1 state (By similarity). {ECO:0000250|UniProtKB:P09626, ECO:0000250|UniProtKB:P19156, ECO:0000250|UniProtKB:Q64436}. |
| P20700 | LMNB1 | S375 | ochoa | Lamin-B1 | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:28716252, PubMed:32910914). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:28716252, PubMed:32910914). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:28716252, PubMed:32910914). {ECO:0000269|PubMed:28716252, ECO:0000269|PubMed:32910914}. |
| P21333 | FLNA | S630 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | S1967 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21399 | ACO1 | S711 | psp | Cytoplasmic aconitate hydratase (Aconitase) (EC 4.2.1.3) (Citrate hydro-lyase) (Ferritin repressor protein) (Iron regulatory protein 1) (IRP1) (Iron-responsive element-binding protein 1) (IRE-BP 1) | Bifunctional iron sensor that switches between 2 activities depending on iron availability (PubMed:1281544, PubMed:1946430, PubMed:8041788). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization (PubMed:1281544, PubMed:1946430, PubMed:23891004, PubMed:8041788). Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA (PubMed:1281544, PubMed:1946430, PubMed:23891004, PubMed:8041788). {ECO:0000269|PubMed:1281544, ECO:0000269|PubMed:1946430, ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:8041788}.; FUNCTION: Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate. {ECO:0000269|PubMed:1281544, ECO:0000269|PubMed:1946430, ECO:0000269|PubMed:8041788}. |
| P21796 | VDAC1 | S193 | psp | Non-selective voltage-gated ion channel VDAC1 (Outer mitochondrial membrane protein porin 1) (Plasmalemmal porin) (Porin 31HL) (Porin 31HM) (Voltage-dependent anion-selective channel protein 1) (VDAC-1) (hVDAC1) | Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:30061676, PubMed:8420959). The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:8420959). It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (PubMed:10661876, PubMed:18755977, PubMed:8420959). The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:18755977, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:18755977, PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Mediates cytochrome c efflux (PubMed:20230784). {ECO:0000250|UniProtKB:Q60932, ECO:0000269|PubMed:10661876, ECO:0000269|PubMed:11845315, ECO:0000269|PubMed:15033708, ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:25296756, ECO:0000269|PubMed:30061676, ECO:0000269|PubMed:31015432, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:8420959}.; FUNCTION: Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids. {ECO:0000269|PubMed:38065946}. |
| P21860 | ERBB3 | S1044 | ochoa | Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-3) (Tyrosine kinase-type cell surface receptor HER3) | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908). {ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:27416908}. |
| P22090 | RPS4Y1 | S204 | ochoa | Small ribosomal subunit protein eS4, Y isoform 1 (40S ribosomal protein S4) | None |
| P22234 | PAICS | S107 | ochoa | Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) [Includes: Phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21) (AIR carboxylase) (AIRC); Phosphoribosylaminoimidazole succinocarboxamide synthetase (EC 6.3.2.6) (SAICAR synthetase)] | Bifunctional phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase catalyzing two reactions of the de novo purine biosynthetic pathway. {ECO:0000269|PubMed:17224163, ECO:0000269|PubMed:2183217, ECO:0000269|PubMed:31600779}. |
| P22314 | UBA1 | S46 | ochoa | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
| P22460 | KCNA5 | S559 | psp | Potassium voltage-gated channel subfamily A member 5 (HPCN1) (Voltage-gated potassium channel HK2) (Voltage-gated potassium channel subunit Kv1.5) | Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:12130714, PubMed:8505626). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). May play a role in regulating the secretion of insulin in normal pancreatic islets. {ECO:0000250|UniProtKB:Q61762, ECO:0000269|PubMed:12130714, ECO:0000269|PubMed:17267549, ECO:0000269|PubMed:20018952, ECO:0000269|PubMed:36917789, ECO:0000269|PubMed:8505626}.; FUNCTION: [Isoform 2]: Exhibits a faster depolarization rate, reduced voltage-dependent recovery from inactivation and an excessive cumulative inactivation. {ECO:0000269|PubMed:11524461}. |
| P22492 | H1-6 | S108 | ochoa | Histone H1t (Testicular H1 histone) | Testis-specific histone H1 that forms less compacted chromatin compared to other H1 histone subtypes (PubMed:26757249). Formation of more relaxed chromatin may be required to promote chromatin architecture required for proper chromosome regulation during meiosis, such as homologous recombination (PubMed:26757249). Histones H1 act as linkers that bind to nucleosomes and compact polynucleosomes into a higher-order chromatin configuration (Probable). {ECO:0000269|PubMed:26757249, ECO:0000305}. |
| P22626 | HNRNPA2B1 | S58 | ochoa | Heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) | Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs (PubMed:19099192). Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm (PubMed:10567417). Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts (PubMed:26321680). Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs (PubMed:24356509). Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs (PubMed:26321680). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). Also plays a role in the activation of the innate immune response (PubMed:31320558). Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6 (PubMed:31320558). In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production (PubMed:31320558). {ECO:0000250|UniProtKB:A7VJC2, ECO:0000269|PubMed:10567417, ECO:0000269|PubMed:20010808, ECO:0000269|PubMed:24356509, ECO:0000269|PubMed:26321680, ECO:0000303|PubMed:19099192}.; FUNCTION: (Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport. {ECO:0000269|PubMed:15294897, ECO:0000269|PubMed:17004321}. |
| P23458 | JAK1 | S537 | ochoa | Tyrosine-protein kinase JAK1 (EC 2.7.10.2) (Janus kinase 1) (JAK-1) | Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16239216, ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:8232552}. |
| P23975 | SLC6A2 | S259 | psp | Sodium-dependent noradrenaline transporter (Norepinephrine transporter) (NET) (Solute carrier family 6 member 2) | Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921, PubMed:39395208, PubMed:39048818). {ECO:0000250|UniProtKB:O55192, ECO:0000269|PubMed:11093780, ECO:0000269|PubMed:2008212, ECO:0000269|PubMed:38750358, ECO:0000269|PubMed:39048818, ECO:0000269|PubMed:8125921}. |
| P24864 | CCNE1 | S381 | ochoa | G1/S-specific cyclin-E1 | Essential for the control of the cell cycle at the G1/S (start) transition. {ECO:0000269|PubMed:7739542}. |
| P25440 | BRD2 | S538 | ochoa | Bromodomain-containing protein 2 (O27.1.1) | Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures (PubMed:17148447, PubMed:17848202, PubMed:18406326, PubMed:20048151, PubMed:20709061, PubMed:20871596). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:28262505). Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation (PubMed:35410381). Also recognizes and binds acetylated non-histone proteins, such as STAT3 (PubMed:28262505). Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin (PubMed:28262505). In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). {ECO:0000269|PubMed:17148447, ECO:0000269|PubMed:17848202, ECO:0000269|PubMed:18406326, ECO:0000269|PubMed:20048151, ECO:0000269|PubMed:20709061, ECO:0000269|PubMed:20871596, ECO:0000269|PubMed:28262505, ECO:0000269|PubMed:35410381, ECO:0000269|PubMed:37731000}. |
| P25705 | ATP5F1A | S166 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P25786 | PSMA1 | S114 | ochoa | Proteasome subunit alpha type-1 (30 kDa prosomal protein) (PROS-30) (Macropain subunit C2) (Multicatalytic endopeptidase complex subunit C2) (Proteasome component C2) (Proteasome nu chain) (Proteasome subunit alpha-6) (alpha-6) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P25815 | S100P | S24 | ochoa | Protein S100-P (Migration-inducing gene 9 protein) (MIG9) (Protein S100-E) (S100 calcium-binding protein P) | May function as calcium sensor and contribute to cellular calcium signaling. In a calcium-dependent manner, functions by interacting with other proteins, such as EZR and PPP5C, and indirectly plays a role in physiological processes like the formation of microvilli in epithelial cells. May stimulate cell proliferation in an autocrine manner via activation of the receptor for activated glycation end products (RAGE). {ECO:0000269|PubMed:14617629, ECO:0000269|PubMed:19111582, ECO:0000269|PubMed:22399290}. |
| P26045 | PTPN3 | S489 | ochoa | Tyrosine-protein phosphatase non-receptor type 3 (EC 3.1.3.48) (Protein-tyrosine phosphatase H1) (PTP-H1) | May act at junctions between the membrane and the cytoskeleton. Possesses tyrosine phosphatase activity. |
| P26232 | CTNNA2 | S42 | ochoa | Catenin alpha-2 (Alpha N-catenin) (Alpha-catenin-related protein) | May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulation of cortical neuronal migration and neurite growth (PubMed:30013181). It acts as a negative regulator of Arp2/3 complex activity and Arp2/3-mediated actin polymerization (PubMed:30013181). It thereby suppresses excessive actin branching which would impair neurite growth and stability (PubMed:30013181). Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation (By similarity). {ECO:0000250|UniProtKB:Q61301, ECO:0000269|PubMed:30013181}. |
| P26583 | HMGB2 | S115 | ochoa | High mobility group protein B2 (High mobility group protein 2) (HMG-2) | Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes. Binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:11909973, PubMed:18413230, PubMed:19522541, PubMed:19965638, PubMed:20123072, PubMed:7797075). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a promiscuous immunogenic DNA/RNA sensor which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). In the extracellular compartment acts as a chemokine. Promotes proliferation and migration of endothelial cells implicating AGER/RAGE (PubMed:19811285). Has antimicrobial activity in gastrointestinal epithelial tissues (PubMed:23877675). Involved in inflammatory response to antigenic stimulus coupled with pro-inflammatory activity (By similarity). Involved in modulation of neurogenesis probably by regulation of neural stem proliferation (By similarity). Involved in articular cartilage surface maintenance implicating LEF1 and the Wnt/beta-catenin pathway (By similarity). {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P30681, ECO:0000269|PubMed:11909973, ECO:0000269|PubMed:18413230, ECO:0000269|PubMed:19522541, ECO:0000269|PubMed:19811285, ECO:0000269|PubMed:19965638, ECO:0000269|PubMed:23877675, ECO:0000269|PubMed:7797075, ECO:0000305|PubMed:20123072}. |
| P26639 | TARS1 | S534 | ochoa | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P26640 | VARS1 | S525 | ochoa | Valine--tRNA ligase (EC 6.1.1.9) (Protein G7a) (Valyl-tRNA synthetase) (ValRS) | Catalyzes the attachment of valine to tRNA(Val). {ECO:0000269|PubMed:8428657}. |
| P26640 | VARS1 | S570 | ochoa | Valine--tRNA ligase (EC 6.1.1.9) (Protein G7a) (Valyl-tRNA synthetase) (ValRS) | Catalyzes the attachment of valine to tRNA(Val). {ECO:0000269|PubMed:8428657}. |
| P27708 | CAD | S1321 | ochoa | Multifunctional protein CAD (Carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase) [Includes: Glutamine-dependent carbamoyl phosphate synthase (EC 6.3.5.5); Glutamine amidotransferase (GATase) (GLNase) (EC 3.5.1.2); Ammonium-dependent carbamoyl phosphate synthase (CPS) (CPSase) (EC 6.3.4.16); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] | Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000269|PubMed:24332717}. |
| P27708 | CAD | S1938 | ochoa | Multifunctional protein CAD (Carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase) [Includes: Glutamine-dependent carbamoyl phosphate synthase (EC 6.3.5.5); Glutamine amidotransferase (GATase) (GLNase) (EC 3.5.1.2); Ammonium-dependent carbamoyl phosphate synthase (CPS) (CPSase) (EC 6.3.4.16); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] | Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000269|PubMed:24332717}. |
| P27815 | PDE4A | S567 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46) (cAMP-specific phosphodiesterase 4A) | Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:11566027, ECO:0000269|PubMed:2160582}.; FUNCTION: [Isoform 1]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 3]: Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP. {ECO:0000269|PubMed:7888306}.; FUNCTION: [Isoform 4]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:9677330}.; FUNCTION: [Isoform 6]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310, ECO:0000269|PubMed:17727341}.; FUNCTION: [Isoform 7]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:18095939}. |
| P27987 | ITPKB | S352 | ochoa | Inositol-trisphosphate 3-kinase B (EC 2.7.1.127) (Inositol 1,4,5-trisphosphate 3-kinase B) (IP3 3-kinase B) (IP3K B) (InsP 3-kinase B) | Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis. {ECO:0000269|PubMed:11846419, ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:1654894}. |
| P28072 | PSMB6 | S58 | ochoa | Proteasome subunit beta type-6 (EC 3.4.25.1) (Macropain delta chain) (Multicatalytic endopeptidase complex delta chain) (Proteasome delta chain) (Proteasome subunit Y) (Proteasome subunit beta-1) (beta-1) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB6 displays a peptidylglutamyl-hydrolizing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues. {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P29083 | GTF2E1 | S292 | ochoa | General transcription factor IIE subunit 1 (General transcription factor IIE 56 kDa subunit) (Transcription initiation factor IIE subunit alpha) (TFIIE-alpha) | Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase. |
| P29084 | GTF2E2 | S61 | ochoa | Transcription initiation factor IIE subunit beta (TFIIE-beta) (General transcription factor IIE subunit 2) | Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase. {ECO:0000269|PubMed:1956398, ECO:0000269|PubMed:1956404}. |
| P29317 | EPHA2 | S775 | ochoa | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P29597 | TYK2 | S613 | ochoa | Non-receptor tyrosine-protein kinase TYK2 (EC 2.7.10.2) | Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862). {ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:10995743, ECO:0000269|PubMed:25762719, ECO:0000269|PubMed:29162862, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7638186, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:8232552}. |
| P30086 | PEBP1 | S109 | ochoa|psp | Phosphatidylethanolamine-binding protein 1 (PEBP-1) (HCNPpp) (Neuropolypeptide h3) (Prostatic-binding protein) (Raf kinase inhibitor protein) (RKIP) [Cleaved into: Hippocampal cholinergic neurostimulating peptide (HCNP)] | Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation. {ECO:0000250, ECO:0000269|PubMed:18294816}.; FUNCTION: HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity). {ECO:0000250}. |
| P30279 | CCND2 | S269 | ochoa | G1/S-specific cyclin-D2 | Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:18827403, PubMed:8114739). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:18827403, PubMed:8114739). Hypophosphorylates RB1 in early G(1) phase (PubMed:18827403, PubMed:8114739). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:18827403, PubMed:8114739). {ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:8114739}. |
| P30307 | CDC25C | S263 | ochoa|psp | M-phase inducer phosphatase 3 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25C) | Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle (PubMed:8119945). When phosphorylated, highly effective in activating G2 cells into prophase (PubMed:8119945). Directly dephosphorylates CDK1 and activates its kinase activity (PubMed:8119945). {ECO:0000269|PubMed:8119945}. |
| P30405 | PPIF | S123 | ochoa|psp | Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIase F) (EC 5.2.1.8) (Cyclophilin D) (CyP-D) (CypD) (Cyclophilin F) (Mitochondrial cyclophilin) (CyP-M) (Rotamase F) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP) (PubMed:26387735). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated (PubMed:26387735). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:22726440). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (By similarity). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (PubMed:19228691). {ECO:0000250|UniProtKB:Q99KR7, ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:26387735}. |
| P30566 | ADSL | S289 | ochoa | Adenylosuccinate lyase (ADSL) (ASL) (EC 4.3.2.2) (Adenylosuccinase) (ASase) | Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate. {ECO:0000269|PubMed:10888601}. |
| P30622 | CLIP1 | S20 | ochoa | CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) | Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}. |
| P30622 | CLIP1 | S204 | ochoa | CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) | Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}. |
| P30679 | GNA15 | S330 | ochoa | Guanine nucleotide-binding protein subunit alpha-15 (G alpha-15) (G-protein subunit alpha-15) (Epididymis tissue protein Li 17E) (Guanine nucleotide-binding protein subunit alpha-16) (G alpha-16) (G-protein subunit alpha-16) | Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. |
| P31321 | PRKAR1B | S238 | ochoa | cAMP-dependent protein kinase type I-beta regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:20819953}. |
| P31327 | CPS1 | S1431 | ochoa | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| P31431 | SDC4 | S97 | ochoa | Syndecan-4 (SYND4) (Amphiglycan) (Ryudocan core protein) | Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413). {ECO:0000269|PubMed:22660413}. |
| P31431 | SDC4 | S179 | psp | Syndecan-4 (SYND4) (Amphiglycan) (Ryudocan core protein) | Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413). {ECO:0000269|PubMed:22660413}. |
| P31629 | HIVEP2 | S314 | ochoa | Transcription factor HIVEP2 (Human immunodeficiency virus type I enhancer-binding protein 2) (HIV-EP2) (MHC-binding protein 2) (MBP-2) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon-beta genes. It may act in T-cell activation. |
| P31629 | HIVEP2 | S2400 | ochoa | Transcription factor HIVEP2 (Human immunodeficiency virus type I enhancer-binding protein 2) (HIV-EP2) (MHC-binding protein 2) (MBP-2) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon-beta genes. It may act in T-cell activation. |
| P31751 | AKT2 | S34 | ochoa | RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-2) (Protein kinase B beta) (PKB beta) (RAC protein kinase beta) (RAC-PK-beta) | Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (PubMed:21432781, PubMed:21620960). In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth (PubMed:31204173). Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion (By similarity). Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation (PubMed:23444369). {ECO:0000250|UniProtKB:Q60823, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:31204173, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.; FUNCTION: Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity). {ECO:0000250|UniProtKB:Q60823}. |
| P31930 | UQCRC1 | S107 | ochoa | Cytochrome b-c1 complex subunit 1, mitochondrial (Complex III subunit 1) (Core protein I) (Ubiquinol-cytochrome-c reductase complex core protein 1) | Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties (By similarity). May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (Probable). Seems to play an important role in the maintenance of proper mitochondrial function in nigral dopaminergic neurons (PubMed:33141179). {ECO:0000250|UniProtKB:P07256, ECO:0000250|UniProtKB:P31800, ECO:0000269|PubMed:33141179, ECO:0000305|PubMed:29243944}. |
| P31939 | ATIC | S565 | ochoa | Bifunctional purine biosynthesis protein ATIC (AICAR transformylase/inosine monophosphate cyclohydrolase) (ATIC) [Cleaved into: Bifunctional purine biosynthesis protein ATIC, N-terminally processed] [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase) (AICAR formyltransferase) (AICAR transformylase); Inosine 5'-monophosphate cyclohydrolase (IMP cyclohydrolase) (EC 3.5.4.10) (IMP synthase) (Inosinicase)] | Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571). {ECO:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:9378707}. |
| P32004 | L1CAM | S1204 | psp | Neural cell adhesion molecule L1 (N-CAM-L1) (NCAM-L1) (CD antigen CD171) | Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity. {ECO:0000269|PubMed:20621658, ECO:0000305}. |
| P32314 | FOXN2 | S273 | ochoa | Forkhead box protein N2 (Human T-cell leukemia virus enhancer factor) | Binds to the purine-rich region in HTLV-I LTR. |
| P32780 | GTF2H1 | S158 | ochoa | General transcription factor IIH subunit 1 (Basic transcription factor 2 62 kDa subunit) (BTF2 p62) (General transcription factor IIH polypeptide 1) (TFIIH basal transcription factor complex p62 subunit) | Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:9852112}. |
| P33176 | KIF5B | S825 | ochoa | Kinesin-1 heavy chain (Conventional kinesin heavy chain) (Ubiquitous kinesin heavy chain) (UKHC) | Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). {ECO:0000250|UniProtKB:Q2PQA9, ECO:0000250|UniProtKB:Q61768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:24088571, ECO:0000305|PubMed:22172677, ECO:0000305|PubMed:24088571}. |
| P33981 | TTK | S49 | ochoa|psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P33981 | TTK | S80 | ochoa|psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P33991 | MCM4 | S120 | ochoa | DNA replication licensing factor MCM4 (EC 3.6.4.12) (CDC21 homolog) (P1-CDC21) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:16899510, PubMed:25661590, PubMed:32453425, PubMed:9305914). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:25661590, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| P34741 | SDC2 | S178 | ochoa | Syndecan-2 (SYND2) (Fibroglycan) (Heparan sulfate proteoglycan core protein) (HSPG) (CD antigen CD362) | Cell surface proteoglycan which regulates dendritic arbor morphogenesis. {ECO:0000250|UniProtKB:P43407}. |
| P34897 | SHMT2 | S226 | ochoa | Serine hydroxymethyltransferase, mitochondrial (SHMT) (EC 2.1.2.1) (Glycine hydroxymethyltransferase) (Serine methylase) | Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:29452640, ECO:0000269|PubMed:33015733}. |
| P35240 | NF2 | S572 | ochoa | Merlin (Moesin-ezrin-radixin-like protein) (Neurofibromin-2) (Schwannomerlin) (Schwannomin) | Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}. |
| P35251 | RFC1 | S173 | ochoa | Replication factor C subunit 1 (Activator 1 140 kDa subunit) (A1 140 kDa subunit) (Activator 1 large subunit) (Activator 1 subunit 1) (DNA-binding protein PO-GA) (Replication factor C 140 kDa subunit) (RF-C 140 kDa subunit) (RFC140) (Replication factor C large subunit) | Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA (PubMed:9488738). This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Can bind single- or double-stranded DNA. {ECO:0000269|PubMed:8999859, ECO:0000269|PubMed:9488738}. |
| P35270 | SPR | S103 | ochoa | Sepiapterin reductase (SPR) (EC 1.1.1.153) | Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin. |
| P35414 | APLNR | S335 | psp | Apelin receptor (Angiotensin receptor-like 1) (G-protein coupled receptor APJ) (G-protein coupled receptor HG11) | G protein-coupled receptor for peptide hormones apelin (APLN) and apelin receptor early endogenous ligand (APELA/ELA), that plays a role in the regulation of normal cardiovascular function and fluid homeostasis (PubMed:11090199, PubMed:22810587, PubMed:25639753, PubMed:28137936, PubMed:35817871, PubMed:38428423). When acting as apelin receptor, activates both G(i) protein pathway that inhibits adenylate cyclase activity, and the beta-arrestin pathway that promotes internalization of the receptor (PubMed:11090199, PubMed:25639753, PubMed:28137936, PubMed:35817871, PubMed:38428423). APLNR/APJ also functions as mechanoreceptor that is activated by pathological stimuli in a G-protein-independent fashion to induce beta-arrestin signaling, hence eliciting cardiac hypertrophy (PubMed:22810587, PubMed:38428423). However, the presence of apelin ligand blunts cardiac hypertrophic induction from APLNR/APJ on response to pathological stimuli (PubMed:22810587, PubMed:38428423). Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a APELA receptor (By similarity). May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Promotes sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Also plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (PubMed:25639753, PubMed:28137936). {ECO:0000250|UniProtKB:Q7SZP9, ECO:0000250|UniProtKB:Q9WV08, ECO:0000269|PubMed:11090199, ECO:0000269|PubMed:22810587, ECO:0000269|PubMed:25639753, ECO:0000269|PubMed:28137936, ECO:0000269|PubMed:35817871, ECO:0000269|PubMed:38428423}.; FUNCTION: (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection; may be involved in the development of AIDS dementia (PubMed:11090199). {ECO:0000269|PubMed:11090199}. |
| P35558 | PCK1 | S19 | ochoa | Phosphoenolpyruvate carboxykinase, cytosolic [GTP] (PEPCK-C) (EC 4.1.1.32) (Serine-protein kinase PCK1) (EC 2.7.11.-) | Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle (PubMed:30193097). At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate (PubMed:30193097). Acts as a regulator of formation and maintenance of memory CD8(+) T-cells: up-regulated in these cells, where it generates phosphoenolpyruvate, via gluconeogenesis (By similarity). The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis (By similarity). In addition to the phosphoenolpyruvate carboxykinase activity, also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor (PubMed:32322062). The protein kinase activity regulates lipogenesis: upon phosphorylation at Ser-90, translocates to the endoplasmic reticulum and catalyzes phosphorylation of INSIG proteins (INSIG1 and INSIG2), thereby disrupting the interaction between INSIG proteins and SCAP and promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes (PubMed:32322062). {ECO:0000250|UniProtKB:Q9Z2V4, ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250, ECO:0000269|PubMed:28216384, ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:32322062}. |
| P35573 | AGL | S582 | ochoa | Glycogen debranching enzyme (Glycogen debrancher) [Includes: 4-alpha-glucanotransferase (EC 2.4.1.25) (Oligo-1,4-1,4-glucantransferase); Amylo-alpha-1,6-glucosidase (Amylo-1,6-glucosidase) (EC 3.2.1.33) (Dextrin 6-alpha-D-glucosidase)] | Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation. |
| P35579 | MYH9 | S1057 | ochoa | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P35606 | COPB2 | S174 | ochoa | Coatomer subunit beta' (Beta'-coat protein) (Beta'-COP) (p102) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. {ECO:0000269|PubMed:34450031}.; FUNCTION: This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner (By similarity). {ECO:0000250}. |
| P35613 | BSG | S362 | ochoa | Basigin (5F7) (Collagenase stimulatory factor) (Extracellular matrix metalloproteinase inducer) (EMMPRIN) (Hepatoma-associated antigen) (HAb18G) (Leukocyte activation antigen M6) (OK blood group antigen) (Tumor cell-derived collagenase stimulatory factor) (TCSF) (CD antigen CD147) | [Isoform 1]: Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes (PubMed:21620857). {ECO:0000250|UniProtKB:P18572, ECO:0000269|PubMed:21620857, ECO:0000269|PubMed:25957687}.; FUNCTION: [Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2. {ECO:0000269|PubMed:22080952}.; FUNCTION: [Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (PubMed:11688976, PubMed:11943775). Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane (PubMed:17127621, PubMed:21778275, PubMed:28666119). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (PubMed:25825981). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells (PubMed:19837976). Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) (PubMed:11992541, PubMed:12553375, PubMed:15833850). {ECO:0000269|PubMed:11688976, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:11992541, ECO:0000269|PubMed:12553375, ECO:0000269|PubMed:15833850, ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:19837976, ECO:0000269|PubMed:21778275, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:28666119}.; FUNCTION: [Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3 (PubMed:22080952, PubMed:26195724). Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866). {ECO:0000269|PubMed:22080952, ECO:0000269|PubMed:26195724, ECO:0000269|PubMed:28409866}.; FUNCTION: [Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:15688292}.; FUNCTION: [Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:11353871}.; FUNCTION: [Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is not required for SARS-CoV-2 infection. {ECO:0000269|PubMed:33432067, ECO:0000303|PubMed:32307653}.; FUNCTION: [Isoform 2]: (Microbial infection) Acts as a receptor for measles virus. {ECO:0000269|PubMed:20147391}.; FUNCTION: [Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells. {ECO:0000269|PubMed:29739904}. |
| P35680 | HNF1B | S80 | ochoa | Hepatocyte nuclear factor 1-beta (HNF-1-beta) (HNF-1B) (Homeoprotein LFB3) (Transcription factor 2) (TCF-2) (Variant hepatic nuclear factor 1) (vHNF1) | Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:17924661, PubMed:7900999). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity). Transcriptional activity is increased by coactivator PCBD1 (PubMed:24204001). {ECO:0000250|UniProtKB:Q03365, ECO:0000269|PubMed:17924661, ECO:0000269|PubMed:24204001, ECO:0000269|PubMed:7900999}. |
| P35749 | MYH11 | S1121 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P35749 | MYH11 | S1756 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P35813 | PPM1A | S190 | ochoa | Protein phosphatase 1A (EC 3.1.3.16) (Protein phosphatase 2C isoform alpha) (PP2C-alpha) (Protein phosphatase IA) | Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:18930133}. |
| P36578 | RPL4 | S55 | ochoa | Large ribosomal subunit protein uL4 (60S ribosomal protein L1) (60S ribosomal protein L4) | Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| P36871 | PGM1 | S509 | ochoa | Phosphoglucomutase-1 (PGM 1) (EC 5.4.2.2) (Glucose phosphomutase 1) | Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate (PubMed:15378030, PubMed:25288802). The mechanism proceeds via the intermediate compound alpha-D-glucose 1,6-bisphosphate (Probable) (PubMed:25288802). This enzyme participates in both the breakdown and synthesis of glucose (PubMed:17924679, PubMed:25288802). {ECO:0000269|PubMed:15378030, ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:25288802, ECO:0000305|PubMed:15378030}. |
| P36897 | TGFBR1 | S191 | psp | TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I) | Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis (PubMed:33914044). The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:33914044, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}. |
| P37198 | NUP62 | S418 | ochoa | Nuclear pore glycoprotein p62 (62 kDa nucleoporin) (Nucleoporin Nup62) | Essential component of the nuclear pore complex (PubMed:1915414). The N-terminal is probably involved in nucleocytoplasmic transport (PubMed:1915414). The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex (PubMed:1915414, PubMed:24107630). Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation (PubMed:24107630). It might be involved in protein recruitment to the centrosome after nuclear breakdown (PubMed:24107630). {ECO:0000269|PubMed:1915414, ECO:0000269|PubMed:24107630}. |
| P37235 | HPCAL1 | S175 | ochoa | Hippocalcin-like protein 1 (Calcium-binding protein BDR-1) (HLP2) (Visinin-like protein 3) (VILIP-3) | May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. |
| P37840 | SNCA | S42 | ochoa | Alpha-synuclein (Non-A beta component of AD amyloid) (Non-A4 component of amyloid precursor) (NACP) | Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:28288128, PubMed:30404828). Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Also acts as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590). {ECO:0000269|PubMed:20798282, ECO:0000269|PubMed:26442590, ECO:0000269|PubMed:28288128, ECO:0000269|PubMed:30404828}. |
| P38398 | BRCA1 | S1101 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P38398 | BRCA1 | S1423 | psp | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P38936 | CDKN1A | S130 | ochoa|psp | Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein 6) (MDA-6) (p21) | Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity). {ECO:0000250|UniProtKB:P39689, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}. |
| P39019 | RPS19 | S74 | ochoa | Small ribosomal subunit protein eS19 (40S ribosomal protein S19) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for pre-rRNA processing and maturation of 40S ribosomal subunits (PubMed:16990592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:16990592, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P39880 | CUX1 | S652 | ochoa | Homeobox protein cut-like 1 (CCAAT displacement protein) (CDP) (CDP/Cux p200) (Homeobox protein cux-1) [Cleaved into: CDP/Cux p110] | Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}. |
| P40189 | IL6ST | S862 | ochoa | Interleukin-6 receptor subunit beta (IL-6 receptor subunit beta) (IL-6R subunit beta) (IL-6R-beta) (IL-6RB) (CDw130) (Interleukin-6 signal transducer) (Membrane glycoprotein 130) (gp130) (Oncostatin-M receptor subunit alpha) (CD antigen CD130) | Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways (PubMed:19915009, PubMed:2261637, PubMed:23294003). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:19915009, PubMed:23294003, PubMed:25731159). In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL27RA/WSX1 and CNTFR (PubMed:19386761). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity). {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:19915009, ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:28747427, ECO:0000269|PubMed:30309848}.; FUNCTION: [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:30279168). {ECO:0000269|PubMed:11121117, ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:30279168}. |
| P41214 | EIF2D | S404 | ochoa | Eukaryotic translation initiation factor 2D (eIF2d) (Hepatocellular carcinoma-associated antigen 56) (Ligatin) | Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. {ECO:0000269|PubMed:20566627, ECO:0000269|PubMed:20713520}. |
| P41279 | MAP3K8 | S141 | ochoa | Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2) | Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19808894}. |
| P42166 | TMPO | S79 | ochoa | Lamina-associated polypeptide 2, isoform alpha (Thymopoietin isoform alpha) (TP alpha) (Thymopoietin-related peptide isoform alpha) (TPRP isoform alpha) [Cleaved into: Thymopoietin (TP) (Splenin); Thymopentin (TP5)] | May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.; FUNCTION: TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide. |
| P42166 | TMPO | S272 | ochoa | Lamina-associated polypeptide 2, isoform alpha (Thymopoietin isoform alpha) (TP alpha) (Thymopoietin-related peptide isoform alpha) (TPRP isoform alpha) [Cleaved into: Thymopoietin (TP) (Splenin); Thymopentin (TP5)] | May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.; FUNCTION: TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide. |
| P42345 | MTOR | S2442 | psp | Serine/threonine-protein kinase mTOR (EC 2.7.11.1) (FK506-binding protein 12-rapamycin complex-associated protein 1) (FKBP12-rapamycin complex-associated protein) (Mammalian target of rapamycin) (mTOR) (Mechanistic target of rapamycin) (Rapamycin and FKBP12 target 1) (Rapamycin target protein 1) (Tyrosine-protein kinase mTOR) (EC 2.7.10.2) | Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23426360, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29424687, ECO:0000269|PubMed:29567957, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31695197, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:35926713, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:36691768, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37751742}. |
| P42356 | PI4KA | S1444 | ochoa | Phosphatidylinositol 4-kinase alpha (PI4-kinase alpha) (PI4K-alpha) (PtdIns-4-kinase alpha) (EC 2.7.1.67) (Phosphatidylinositol 4-Kinase III alpha) | Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate. {ECO:0000269|PubMed:10101268, ECO:0000269|PubMed:23229899}. |
| P42704 | LRPPRC | S121 | ochoa | Leucine-rich PPR motif-containing protein, mitochondrial (130 kDa leucine-rich protein) (LRP 130) (GP130) | May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. Positively modulates nuclear export of mRNAs containing the EIF4E sensitivity element (4ESE) by binding simultaneously to both EIF4E and the 4ESE and acting as a platform for assembly for the RNA export complex (PubMed:19262567, PubMed:28325843). Also binds to exportin XPO1/CRM1 to engage the nuclear pore and traffic the bound mRNAs to the cytoplasm (PubMed:28325843). May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mitochondrially encoded genes and gluconeogenic genes and may regulate docking of PPARGC1A to transcription factors. Seems to be involved in the transcription regulation of the multidrug-related genes MDR1 and MVP. Part of a nuclear factor that binds to the invMED1 element of MDR1 and MVP gene promoters. Binds single-stranded DNA (By similarity). Required for maintaining mitochondrial potential (PubMed:23822101). Suppresses the initiation of basal levels of autophagy and mitophagy by sustaining BCL2 levels (PubMed:23822101). {ECO:0000250, ECO:0000269|PubMed:11585913, ECO:0000269|PubMed:12832482, ECO:0000269|PubMed:15081402, ECO:0000269|PubMed:15139850, ECO:0000269|PubMed:15272088, ECO:0000269|PubMed:17050673, ECO:0000269|PubMed:19262567, ECO:0000269|PubMed:23822101, ECO:0000269|PubMed:28325843}. |
| P42765 | ACAA2 | S357 | ochoa | 3-ketoacyl-CoA thiolase, mitochondrial (EC 2.3.1.16) (Acetyl-CoA acetyltransferase) (EC 2.3.1.9) (Acetyl-CoA acyltransferase) (Acyl-CoA hydrolase, mitochondrial) (EC 3.1.2.-, EC 3.1.2.1, EC 3.1.2.2) (Beta-ketothiolase) (Mitochondrial 3-oxoacyl-CoA thiolase) (T1) | In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (Probable). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (Probable). Also catalyzes the condensation of two acetyl-CoA molecules into acetoacetyl-CoA and could be involved in the production of ketone bodies (Probable). Also displays hydrolase activity on various fatty acyl-CoAs (PubMed:25478839). Thereby, could be responsible for the production of acetate in a side reaction to beta-oxidation (Probable). Abolishes BNIP3-mediated apoptosis and mitochondrial damage (PubMed:18371312). {ECO:0000269|PubMed:18371312, ECO:0000269|PubMed:25478839, ECO:0000305|PubMed:25478839}. |
| P42766 | RPL35 | S29 | ochoa | Large ribosomal subunit protein uL29 (60S ribosomal protein L35) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P42858 | HTT | S489 | psp | Huntingtin (Huntington disease protein) (HD protein) [Cleaved into: Huntingtin, myristoylated N-terminal fragment] | [Huntingtin]: May play a role in microtubule-mediated transport or vesicle function.; FUNCTION: [Huntingtin, myristoylated N-terminal fragment]: Promotes the formation of autophagic vesicles. {ECO:0000269|PubMed:24459296}. |
| P43121 | MCAM | S628 | ochoa | Cell surface glycoprotein MUC18 (Cell surface glycoprotein P1H12) (Melanoma cell adhesion molecule) (Melanoma-associated antigen A32) (Melanoma-associated antigen MUC18) (S-endo 1 endothelial-associated antigen) (CD antigen CD146) | Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as a surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration. {ECO:0000269|PubMed:11036077, ECO:0000269|PubMed:8292890}. |
| P43489 | TNFRSF4 | S258 | ochoa | Tumor necrosis factor receptor superfamily member 4 (ACT35 antigen) (OX40L receptor) (TAX transcriptionally-activated glycoprotein 1 receptor) (CD antigen CD134) | Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity. {ECO:0000269|PubMed:7704935}.; FUNCTION: (Microbial infection) Acts as a receptor for human herpesvirus 6B/HHV-6B. {ECO:0000269|PubMed:23674671}. |
| P45974 | USP5 | S715 | ochoa | Ubiquitin carboxyl-terminal hydrolase 5 (EC 3.4.19.12) (Deubiquitinating enzyme 5) (Isopeptidase T) (Ubiquitin thioesterase 5) (Ubiquitin-specific-processing protease 5) | Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter (PubMed:26912724). Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains (PubMed:29567855). Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein (PubMed:37534934). Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1 (PubMed:37208329). Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels (PubMed:37607937). Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3 (PubMed:39761299). Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4 (PubMed:39032648). Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination (PubMed:39900921). May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity). {ECO:0000250|UniProtKB:P56399, ECO:0000269|PubMed:19098288, ECO:0000269|PubMed:26912724, ECO:0000269|PubMed:29567855, ECO:0000269|PubMed:37208329, ECO:0000269|PubMed:37534934, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:39761299, ECO:0000269|PubMed:39900921}. |
| P45983 | MAPK8 | S179 | ochoa | Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1) | Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:28943315, ECO:0000269|PubMed:34048572}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. |
| P46013 | MKI67 | S1207 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1329 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1693 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1721 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1815 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1937 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2299 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2420 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2542 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46060 | RANGAP1 | S24 | ochoa | Ran GTPase-activating protein 1 (RanGAP1) | GTPase activator for RAN (PubMed:16428860, PubMed:8146159, PubMed:8896452). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:27160050, PubMed:8896452). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). {ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}. |
| P46108 | CRK | S125 | ochoa | Adapter molecule crk (Proto-oncogene c-Crk) (p38) | Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1. {ECO:0000269|PubMed:12432078}.; FUNCTION: [Isoform Crk-II]: Regulates cell adhesion, spreading and migration (PubMed:31311869). Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4 (PubMed:19004829). May regulate the EFNA5-EPHA3 signaling (By similarity). {ECO:0000250|UniProtKB:Q64010, ECO:0000269|PubMed:11870224, ECO:0000269|PubMed:1630456, ECO:0000269|PubMed:17515907, ECO:0000269|PubMed:19004829, ECO:0000269|PubMed:31311869}. |
| P46531 | NOTCH1 | S2148 | ochoa | Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). {ECO:0000269|PubMed:20616313}. |
| P46821 | MAP1B | S1512 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P46939 | UTRN | S2821 | ochoa | Utrophin (Dystrophin-related protein 1) (DRP-1) | May play a role in anchoring the cytoskeleton to the plasma membrane. {ECO:0000250}. |
| P46940 | IQGAP1 | S19 | ochoa | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| P46976 | GYG1 | S46 | ochoa | Glycogenin-1 (GN-1) (GN1) (EC 2.4.1.186) | Glycogenin participates in the glycogen biosynthetic process along with glycogen synthase and glycogen branching enzyme. It catalyzes the formation of a short alpha (1,4)-glucosyl chain covalently attached via a glucose 1-O-tyrosyl linkage to internal tyrosine residues and these chains act as primers for the elongation reaction catalyzed by glycogen synthase. {ECO:0000269|PubMed:22160680, ECO:0000269|PubMed:30356213}. |
| P47712 | PLA2G4A | S515 | psp | Cytosolic phospholipase A2 (cPLA2) (Phospholipase A2 group IVA) [Includes: Phospholipase A2 (EC 3.1.1.4) (Phosphatidylcholine 2-acylhydrolase); Lysophospholipase (EC 3.1.1.5)] | Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891). {ECO:0000250|UniProtKB:P47713, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:12672805, ECO:0000269|PubMed:14709560, ECO:0000269|PubMed:16617059, ECO:0000269|PubMed:17472963, ECO:0000269|PubMed:18451993, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7794891, ECO:0000269|PubMed:8619991, ECO:0000269|PubMed:8702602, ECO:0000269|PubMed:9425121}. |
| P47756 | CAPZB | S192 | psp | F-actin-capping protein subunit beta (CapZ beta) | F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:A9XFX6, ECO:0000269|PubMed:21834987}. |
| P48200 | IREB2 | S177 | ochoa | Iron-responsive element-binding protein 2 (IRE-BP 2) (Iron regulatory protein 2) (IRP2) | RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA. {ECO:0000269|PubMed:7983023}. |
| P48444 | ARCN1 | S253 | ochoa | Coatomer subunit delta (Archain) (Delta-coat protein) (Delta-COP) | Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| P48553 | TRAPPC10 | S1175 | ochoa | Trafficking protein particle complex subunit 10 (Epilepsy holoprosencephaly candidate 1 protein) (EHOC-1) (Protein GT334) (Trafficking protein particle complex subunit TMEM1) (Transport protein particle subunit TMEM1) (TRAPP subunit TMEM1) | Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether. {ECO:0000269|PubMed:11805826, ECO:0000269|PubMed:31467083, ECO:0000269|PubMed:35298461}. |
| P48634 | PRRC2A | S2073 | ochoa | Protein PRRC2A (HLA-B-associated transcript 2) (Large proline-rich protein BAT2) (Proline-rich and coiled-coil-containing protein 2A) (Protein G2) | May play a role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:14667819}. |
| P48651 | PTDSS1 | S439 | ochoa | Phosphatidylserine synthase 1 (PSS-1) (PtdSer synthase 1) (EC 2.7.8.29) (Serine-exchange enzyme I) | Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (PubMed:19014349, PubMed:24241535). Catalyzes mainly the conversion of phosphatidylcholine (PubMed:19014349, PubMed:24241535). Also converts, in vitro and to a lesser extent, phosphatidylethanolamine (PubMed:19014349, PubMed:24241535). {ECO:0000269|PubMed:19014349, ECO:0000269|PubMed:24241535}. |
| P49023 | PXN | S340 | ochoa | Paxillin | Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion. {ECO:0000269|PubMed:25015296}. |
| P49137 | MAPKAPK2 | S216 | ochoa | MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) | Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}. |
| P49189 | ALDH9A1 | S233 | ochoa | 4-trimethylaminobutyraldehyde dehydrogenase (TMABA-DH) (TMABALDH) (EC 1.2.1.47) (Aldehyde dehydrogenase E3 isozyme) (Aldehyde dehydrogenase family 9 member A1) (EC 1.2.1.3) (Formaldehyde dehydrogenase) (EC 1.2.1.46) (Gamma-aminobutyraldehyde dehydrogenase) (EC 1.2.1.19) (R-aminobutyraldehyde dehydrogenase) [Cleaved into: 4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processed] | Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro). Can catalyze the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, but with low efficiency. Catalyzes the oxidation of aldehydes arising from biogenic amines and polyamines. {ECO:0000269|PubMed:10702312, ECO:0000269|PubMed:1799975, ECO:0000269|PubMed:30914451, ECO:0000269|PubMed:8645224}. |
| P49247 | RPIA | S106 | ochoa | Ribose-5-phosphate isomerase (EC 5.3.1.6) (Phosphoriboisomerase) | Catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate and participates in the first step of the non-oxidative branch of the pentose phosphate pathway. {ECO:0000269|PubMed:14988808}. |
| P49257 | LMAN1 | S425 | ochoa | Protein ERGIC-53 (ER-Golgi intermediate compartment 53 kDa protein) (Gp58) (Intracellular mannose-specific lectin MR60) (Lectin mannose-binding 1) | Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:13130098}. |
| P49327 | FASN | S2156 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49327 | FASN | S2198 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49427 | CDC34 | S203 | psp | Ubiquitin-conjugating enzyme E2 R1 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme R1) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme R1) (Ubiquitin-conjugating enzyme E2-32 kDa complementing) (Ubiquitin-conjugating enzyme E2-CDC34) (Ubiquitin-protein ligase R1) | E2 ubiquitin-conjugating enzyme that accepts ubiquitin from an E1 ubiquitin-activating protein, and catalyzes its covalent attachment to other proteins by an E3 ubiquitin-protein ligase complex (PubMed:10329681, PubMed:17588522, PubMed:20061386, PubMed:38326650). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:22496338). Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:10329681, PubMed:10918611, PubMed:17698585). Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1 (PubMed:10871850, PubMed:15652359, PubMed:19112177). Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation (PubMed:19126550). Also involved in the degradation of beta-catenin (PubMed:12037680). Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes (PubMed:11805320, PubMed:12060736). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10871850, ECO:0000269|PubMed:10918611, ECO:0000269|PubMed:11805320, ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:12060736, ECO:0000269|PubMed:15652359, ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19126550, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338, ECO:0000269|PubMed:38326650}. |
| P49591 | SARS1 | S101 | psp | Serine--tRNA ligase, cytoplasmic (EC 6.1.1.11) (Seryl-tRNA synthetase) (SerRS) (Seryl-tRNA(Ser/Sec) synthetase) | Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:36041817, PubMed:9431993). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:9431993). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423847, PubMed:19423848, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:34570399, ECO:0000269|PubMed:36041817, ECO:0000269|PubMed:9431993}. |
| P49790 | NUP153 | S607 | ochoa | Nuclear pore complex protein Nup153 (153 kDa nucleoporin) (Nucleoporin Nup153) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC). {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22253824}.; FUNCTION: (Microbial infection) Interacts with HIV-1 caspid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro). {ECO:0000269|PubMed:23523133, ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:29997211}.; FUNCTION: (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro). {ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:31913756}. |
| P49792 | RANBP2 | S18 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S380 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49796 | RGS3 | S992 | ochoa | Regulator of G-protein signaling 3 (RGP3) (RGS3) | Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form. Down-regulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. {ECO:0000269|PubMed:10749886, ECO:0000269|PubMed:11294858, ECO:0000269|PubMed:8602223, ECO:0000269|PubMed:9858594}. |
| P49917 | LIG4 | S854 | ochoa | DNA ligase 4 (EC 6.5.1.1) (DNA ligase IV) (Polydeoxyribonucleotide synthase [ATP] 4) | DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242410, PubMed:9809069). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242). {ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:23523427, ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:29980672, ECO:0000269|PubMed:33586762, ECO:0000269|PubMed:8798671, ECO:0000269|PubMed:9242410, ECO:0000269|PubMed:9809069}. |
| P50148 | GNAQ | S53 | psp | Guanine nucleotide-binding protein G(q) subunit alpha (EC 3.6.5.-) (Guanine nucleotide-binding protein alpha-q) | Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:37991948). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:37991948). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:37991948). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:37991948). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:37991948). Signaling is mediated via phospholipase C-beta-dependent inositol lipid hydrolysis for signal propagation: activates phospholipase C-beta: following GPCR activation, GNAQ activates PLC-beta (PLCB1, PLCB2, PLCB3 or PLCB4), leading to production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (PubMed:37991948). Required for platelet activation (By similarity). Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity (By similarity). Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (By similarity). Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs) (PubMed:27852822). Together with GNA11, required for heart development (By similarity). {ECO:0000250|UniProtKB:P21279, ECO:0000269|PubMed:27852822, ECO:0000269|PubMed:37991948}. |
| P50336 | PPOX | S213 | ochoa | Protoporphyrinogen oxidase (PPO) (EC 1.3.3.4) | Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX. {ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23467411, ECO:0000269|PubMed:7713909}. |
| P50402 | EMD | S29 | ochoa | Emerin | Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. {ECO:0000269|PubMed:15328537, ECO:0000269|PubMed:16680152, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17785515, ECO:0000269|PubMed:19323649, ECO:0000269|PubMed:32923640}. |
| P50402 | EMD | S87 | ochoa | Emerin | Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. {ECO:0000269|PubMed:15328537, ECO:0000269|PubMed:16680152, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17785515, ECO:0000269|PubMed:19323649, ECO:0000269|PubMed:32923640}. |
| P50454 | SERPINH1 | S132 | ochoa | Serpin H1 (47 kDa heat shock protein) (Arsenic-transactivated protein 3) (AsTP3) (Cell proliferation-inducing gene 14 protein) (Collagen-binding protein) (Colligin) (Rheumatoid arthritis-related antigen RA-A47) | Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen. |
| P50613 | CDK7 | S164 | ochoa|psp | Cyclin-dependent kinase 7 (EC 2.7.11.22) (EC 2.7.11.23) (39 kDa protein kinase) (p39 Mo15) (CDK-activating kinase 1) (Cell division protein kinase 7) (Serine/threonine-protein kinase 1) (TFIIH basal transcription factor complex kinase subunit) | Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription (PubMed:9852112, PubMed:19136461, PubMed:26257281, PubMed:28768201). Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201). Initiates transcription by RNA polymerase II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, PubMed:28768201). CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the CTD of POLR2A, allowing its escape from the promoter and elongation of the transcripts (PubMed:9852112). Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130, ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173, ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:28768201, ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}. |
| P50993 | ATP1A2 | S367 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-2) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P51003 | PAPOLA | S552 | ochoa | Poly(A) polymerase alpha (PAP-alpha) (EC 2.7.7.19) (Polynucleotide adenylyltransferase alpha) | Polymerase that creates the 3'-poly(A) tail of mRNA's. Also required for the endoribonucleolytic cleavage reaction at some polyadenylation sites. May acquire specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus. {ECO:0000269|PubMed:19224921}. |
| P51116 | FXR2 | S397 | ochoa | RNA-binding protein FXR2 (FXR2P) (FMR1 autosomal homolog 2) | mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for adult hippocampal neurogenesis (By similarity). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs: mRNAs storage into membraneless compartments regulates their translation and/or stability (By similarity). Acts as a regulator of adult hippocampal neurogenesis by regulating translation and/or stability of NOG mRNA, thereby preventing NOG protein expression in the dentate gyrus (By similarity). {ECO:0000250|UniProtKB:Q61584, ECO:0000250|UniProtKB:Q9WVR4}. |
| P51116 | FXR2 | S401 | ochoa | RNA-binding protein FXR2 (FXR2P) (FMR1 autosomal homolog 2) | mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for adult hippocampal neurogenesis (By similarity). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs: mRNAs storage into membraneless compartments regulates their translation and/or stability (By similarity). Acts as a regulator of adult hippocampal neurogenesis by regulating translation and/or stability of NOG mRNA, thereby preventing NOG protein expression in the dentate gyrus (By similarity). {ECO:0000250|UniProtKB:Q61584, ECO:0000250|UniProtKB:Q9WVR4}. |
| P51531 | SMARCA2 | S588 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SAMRCA2) (EC 3.6.4.-) (BRG1-associated factor 190B) (BAF190B) (Probable global transcription activator SNF2L2) (Protein brahma homolog) (hBRM) (SNF2-alpha) | ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:15075294, PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6DIC0, ECO:0000269|PubMed:15075294, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P51587 | BRCA2 | S1339 | ochoa | Breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein) | Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}. |
| P51608 | MECP2 | S149 | ochoa | Methyl-CpG-binding protein 2 (MeCp-2 protein) (MeCp2) | Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC). {ECO:0000250|UniProtKB:Q9Z2D6}. |
| P51610 | HCFC1 | S674 | ochoa | Host cell factor 1 (HCF) (HCF-1) (C1 factor) (CFF) (VCAF) (VP16 accessory protein) [Cleaved into: HCF N-terminal chain 1; HCF N-terminal chain 2; HCF N-terminal chain 3; HCF N-terminal chain 4; HCF N-terminal chain 5; HCF N-terminal chain 6; HCF C-terminal chain 1; HCF C-terminal chain 2; HCF C-terminal chain 3; HCF C-terminal chain 4; HCF C-terminal chain 5; HCF C-terminal chain 6] | Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity). {ECO:0000250|UniProtKB:D3ZN95, ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26416877}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:17578910}. |
| P51610 | HCFC1 | S1070 | psp | Host cell factor 1 (HCF) (HCF-1) (C1 factor) (CFF) (VCAF) (VP16 accessory protein) [Cleaved into: HCF N-terminal chain 1; HCF N-terminal chain 2; HCF N-terminal chain 3; HCF N-terminal chain 4; HCF N-terminal chain 5; HCF N-terminal chain 6; HCF C-terminal chain 1; HCF C-terminal chain 2; HCF C-terminal chain 3; HCF C-terminal chain 4; HCF C-terminal chain 5; HCF C-terminal chain 6] | Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity). {ECO:0000250|UniProtKB:D3ZN95, ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26416877}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:17578910}. |
| P51812 | RPS6KA3 | S78 | ochoa | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
| P51825 | AFF1 | S717 | ochoa | AF4/FMR2 family member 1 (ALL1-fused gene from chromosome 4 protein) (Protein AF-4) (Protein FEL) (Proto-oncogene AF4) | None |
| P51955 | NEK2 | S356 | psp | Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) | Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856, ECO:0000269|PubMed:30404835}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}. |
| P51955 | NEK2 | S377 | ochoa | Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) | Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856, ECO:0000269|PubMed:30404835}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}. |
| P52630 | STAT2 | S381 | psp | Signal transducer and activator of transcription 2 (p113) | Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state (PubMed:23391734, PubMed:9020188). In addition, also has a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs (PubMed:28165510). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:23391734, PubMed:26122121, PubMed:9020188). {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121, ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142, ECO:0000269|PubMed:9020188}. |
| P52701 | MSH6 | S309 | ochoa|psp | DNA mismatch repair protein Msh6 (hMSH6) (G/T mismatch-binding protein) (GTBP) (GTMBP) (MutS protein homolog 6) (MutS-alpha 160 kDa subunit) (p160) | Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}. |
| P52943 | CRIP2 | S74 | ochoa | Cysteine-rich protein 2 (CRP-2) (Protein ESP1) | None |
| P53004 | BLVRA | S149 | psp | Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) | Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}. |
| P53007 | SLC25A1 | S94 | ochoa | Tricarboxylate transport protein, mitochondrial (Citrate transport protein) (CTP) (Mitochondrial citrate carrier) (CIC) (Solute carrier family 25 member 1) (Tricarboxylate carrier protein) | Mitochondrial electroneutral antiporter that exports citrate from the mitochondria into the cytosol in exchange for malate (PubMed:26870663, PubMed:29031613, PubMed:29238895, PubMed:39881208). Also able to mediate the exchange of citrate for isocitrate, phosphoenolpyruvate, cis-aconitate and to a lesser extent trans-aconitate, maleate and succinate (PubMed:29031613). In the cytoplasm, citrate plays important roles in fatty acid and sterol synthesis, regulation of glycolysis, protein acetylation, and other physiopathological processes (PubMed:29031613, PubMed:29238895, PubMed:39881208). {ECO:0000269|PubMed:26870663, ECO:0000269|PubMed:29031613, ECO:0000269|PubMed:29238895, ECO:0000269|PubMed:39881208}. |
| P53602 | MVD | S211 | ochoa | Diphosphomevalonate decarboxylase (EC 4.1.1.33) (Mevalonate (diphospho)decarboxylase) (MDDase) (Mevalonate pyrophosphate decarboxylase) | Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoids and sterol synthesis. {ECO:0000269|PubMed:18823933, ECO:0000269|PubMed:8626466, ECO:0000269|PubMed:9392419}. |
| P53779 | MAPK10 | S217 | ochoa | Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (MAP kinase p49 3F12) (Stress-activated protein kinase 1b) (SAPK1b) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3) | Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000269|PubMed:11718727, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692}. |
| P54105 | CLNS1A | S50 | ochoa | Methylosome subunit pICln (Chloride channel, nucleotide sensitive 1A) (Chloride conductance regulatory protein ICln) (I(Cln)) (Chloride ion current inducer protein) (ClCI) (Reticulocyte pICln) | Involved in both the assembly of spliceosomal snRNPs and the methylation of Sm proteins (PubMed:10330151, PubMed:11713266, PubMed:18984161, PubMed:21081503). Chaperone that regulates the assembly of spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (PubMed:10330151, PubMed:18984161). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (PubMed:10330151). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (PubMed:10330151, PubMed:18984161). Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus (PubMed:10330151, PubMed:18984161). {ECO:0000269|PubMed:10330151, ECO:0000269|PubMed:11713266, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21081503}. |
| P54252 | ATXN3 | S260 | psp | Ataxin-3 (EC 3.4.19.12) (Machado-Joseph disease protein 1) (Spinocerebellar ataxia type 3 protein) | Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:16118278, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:33157014). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (PubMed:17696782). Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (PubMed:12297501). Acts as a negative regulator of mTORC1 signaling in response to amino acid deprivation by mediating deubiquitination of RHEB, thereby promoting RHEB inactivation by the TSC-TBC complex (PubMed:33157014). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460). {ECO:0000250|UniProtKB:Q9CVD2, ECO:0000269|PubMed:12297501, ECO:0000269|PubMed:16118278, ECO:0000269|PubMed:17696782, ECO:0000269|PubMed:23625928, ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:33157014}. |
| P54253 | ATXN1 | S82 | ochoa | Ataxin-1 (Spinocerebellar ataxia type 1 protein) | Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Binds RNA in vitro. May be involved in RNA metabolism (PubMed:21475249). In concert with CIC and ATXN1L, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P54254, ECO:0000269|PubMed:21475249}. |
| P54277 | PMS1 | S673 | ochoa | PMS1 protein homolog 1 (DNA mismatch repair protein PMS1) | Probably involved in the repair of mismatches in DNA. {ECO:0000269|PubMed:10748105}. |
| P54278 | PMS2 | S513 | ochoa | Mismatch repair endonuclease PMS2 (EC 3.1.-.-) (DNA mismatch repair protein PMS2) (PMS1 protein homolog 2) | Component of the post-replicative DNA mismatch repair system (MMR) (PubMed:30653781, PubMed:35189042). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Possesses an ATPase activity, but in the absence of gross structural changes, ATP hydrolysis may not be necessary for proficient mismatch repair (PubMed:35189042). {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:23709753, ECO:0000269|PubMed:30653781, ECO:0000269|PubMed:35189042}. |
| P54296 | MYOM2 | S192 | ochoa | Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P54296 | MYOM2 | S553 | ochoa | Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P54652 | HSPA2 | S224 | ochoa | Heat shock-related 70 kDa protein 2 (Heat shock 70 kDa protein 2) (Heat shock protein family A member 2) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity). {ECO:0000250|UniProtKB:P17156, ECO:0000303|PubMed:26865365}. |
| P54760 | EPHB4 | S911 | ochoa | Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}. |
| P54762 | EPHB1 | S899 | ochoa | Ephrin type-B receptor 1 (EC 2.7.10.1) (ELK) (EPH tyrosine kinase 2) (EPH-like kinase 6) (EK6) (hEK6) (Neuronally-expressed EPH-related tyrosine kinase) (NET) (Tyrosine-protein kinase receptor EPH-2) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}. |
| P55055 | NR1H2 | S426 | psp | Oxysterols receptor LXR-beta (Liver X receptor beta) (Nuclear receptor NER) (Nuclear receptor subfamily 1 group H member 2) (Ubiquitously-expressed nuclear receptor) | Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (By similarity). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). {ECO:0000250|UniProtKB:Q60644, ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:25661920}. |
| P55072 | VCP | S37 | ochoa | Transitional endoplasmic reticulum ATPase (TER ATPase) (EC 3.6.4.6) (15S Mg(2+)-ATPase p97 subunit) (Valosin-containing protein) (VCP) | Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Involved in clearance process by mediating G3BP1 extraction from stress granules (PubMed:29804830, PubMed:34739333). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042605, PubMed:23042607). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (PubMed:35013556). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:P23787, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:35013556}. |
| P55072 | VCP | S770 | ochoa | Transitional endoplasmic reticulum ATPase (TER ATPase) (EC 3.6.4.6) (15S Mg(2+)-ATPase p97 subunit) (Valosin-containing protein) (VCP) | Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Involved in clearance process by mediating G3BP1 extraction from stress granules (PubMed:29804830, PubMed:34739333). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042605, PubMed:23042607). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (PubMed:35013556). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:P23787, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:35013556}. |
| P55082 | MFAP3 | S331 | ochoa | Microfibril-associated glycoprotein 3 | Component of the elastin-associated microfibrils. |
| P55197 | MLLT10 | S278 | ochoa | Protein AF-10 (ALL1-fused gene from chromosome 10 protein) | Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (PubMed:26439302). {ECO:0000269|PubMed:17868029, ECO:0000269|PubMed:26439302}. |
| P55197 | MLLT10 | S527 | ochoa | Protein AF-10 (ALL1-fused gene from chromosome 10 protein) | Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (PubMed:26439302). {ECO:0000269|PubMed:17868029, ECO:0000269|PubMed:26439302}. |
| P55786 | NPEPPS | S811 | ochoa | Puromycin-sensitive aminopeptidase (PSA) (EC 3.4.11.14) (Cytosol alanyl aminopeptidase) (AAP-S) | Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain. {ECO:0000269|PubMed:10978616, ECO:0000269|PubMed:11062501, ECO:0000269|PubMed:17154549, ECO:0000269|PubMed:17318184, ECO:0000269|PubMed:19917696}. |
| P56182 | RRP1 | S272 | ochoa | Ribosomal RNA processing protein 1 homolog A (Novel nuclear protein 1) (NNP-1) (Nucleolar protein Nop52) (RRP1-like protein) | Plays a critical role in the generation of 28S rRNA. {ECO:0000269|PubMed:10341208}. |
| P56211 | ARPP19 | S46 | psp | cAMP-regulated phosphoprotein 19 (ARPP-19) | Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis (PubMed:38123684). Inhibition of PP2A is enhanced when ARPP19 is phosphorylated (PubMed:38123684). When phosphorylated at Ser-62 during mitosis, specifically interacts with PPP2R2D (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase (PubMed:21164014). May indirectly enhance GAP-43 expression (By similarity). {ECO:0000250|UniProtKB:Q712U5, ECO:0000269|PubMed:21164014, ECO:0000269|PubMed:38123684}. |
| P57053 | H2BC12L | S57 | ochoa | Histone H2B type F-S (H2B-clustered histone 12 like) (H2B.S histone 1) (Histone H2B.s) (H2B/s) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.; FUNCTION: Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid. |
| P57721 | PCBP3 | S143 | ochoa | Poly(rC)-binding protein 3 (Alpha-CP3) (PCBP3-overlapping transcript) (PCBP3-overlapping transcript 1) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. {ECO:0000250}. |
| P58876 | H2BC5 | S57 | ochoa | Histone H2B type 1-D (H2B-clustered histone 5) (HIRA-interacting protein 2) (Histone H2B.1 B) (Histone H2B.b) (H2B/b) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| P60484 | PTEN | S294 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (EC 3.1.3.16) (EC 3.1.3.48) (EC 3.1.3.67) (Inositol polyphosphate 3-phosphatase) (EC 3.1.3.-) (Mutated in multiple advanced cancers 1) (Phosphatase and tensin homolog) | Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3 (PubMed:16824732, PubMed:26504226, PubMed:9593664, PubMed:9811831). Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate (PubMed:11418101, PubMed:15979280). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:31492966, PubMed:37279284). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (PubMed:22279049). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (PubMed:26166433). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (PubMed:26166433). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability (PubMed:10468583, PubMed:18716620). {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:10468583, ECO:0000269|PubMed:11418101, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:15979280, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26504226, ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:37279284, ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433, ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9616126, ECO:0000269|PubMed:9811831}.; FUNCTION: [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1. {ECO:0000269|PubMed:23744781}. |
| P60983 | GMFB | S72 | psp | Glia maturation factor beta (GMF-beta) | This protein causes differentiation of brain cells, stimulation of neural regeneration, and inhibition of proliferation of tumor cells. |
| P61073 | CXCR4 | S312 | ochoa | C-X-C chemokine receptor type 4 (CXC-R4) (CXCR-4) (FB22) (Fusin) (HM89) (LCR1) (Leukocyte-derived seven transmembrane domain receptor) (LESTR) (Lipopolysaccharide-associated protein 3) (LAP-3) (LPS-associated protein 3) (NPYRL) (Stromal cell-derived factor 1 receptor) (SDF-1 receptor) (CD antigen CD184) | Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10452968, PubMed:18799424, PubMed:24912431, PubMed:28978524). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (By similarity). {ECO:0000250|UniProtKB:P70658, ECO:0000269|PubMed:10074102, ECO:0000269|PubMed:10452968, ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:10825158, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:17197449, ECO:0000269|PubMed:18799424, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:20228059, ECO:0000269|PubMed:20505072, ECO:0000269|PubMed:24912431, ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:8752280, ECO:0000269|PubMed:8752281}.; FUNCTION: (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus (PubMed:10074122, PubMed:10756055, PubMed:8849450, PubMed:8929542, PubMed:9427609). {ECO:0000269|PubMed:10074122, ECO:0000269|PubMed:10756055, ECO:0000269|PubMed:8849450, ECO:0000269|PubMed:8929542, ECO:0000269|PubMed:9427609}. |
| P61106 | RAB14 | S180 | ochoa | Ras-related protein Rab-14 (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:22595670). Involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development (By similarity). Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes (By similarity). Regulates, together with its guanine nucleotide exchange factor DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion (PubMed:22595670). Mediates endosomal tethering and fusion through the interaction with RUFY1 and RAB4B (PubMed:20534812). Interaction with RAB11FIP1 may function in the process of neurite formation (PubMed:26032412). {ECO:0000250|UniProtKB:P61107, ECO:0000250|UniProtKB:Q91V41, ECO:0000269|PubMed:20534812, ECO:0000269|PubMed:22595670, ECO:0000269|PubMed:26032412}. |
| P61221 | ABCE1 | S423 | ochoa | ATP-binding cassette sub-family E member 1 (EC 3.6.5.-) (2'-5'-oligoadenylate-binding protein) (HuHP68) (RNase L inhibitor) (Ribonuclease 4 inhibitor) (RNS4I) | Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly (PubMed:20122402, PubMed:21448132). Able to hydrolyze ATP, GTP, UTP and CTP (PubMed:20122402). Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits (PubMed:20122402, PubMed:21448132). Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota) (PubMed:20122402, PubMed:21448132). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132). Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA (PubMed:29861391). As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy (PubMed:29861391). RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) to RNASEL (PubMed:9660177). Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway (PubMed:11585831, PubMed:9660177, PubMed:9847332). {ECO:0000269|PubMed:11585831, ECO:0000269|PubMed:20122402, ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:29861391, ECO:0000269|PubMed:9660177, ECO:0000269|PubMed:9847332}.; FUNCTION: (Microbial infection) May act as a chaperone for post-translational events during HIV-1 capsid assembly. {ECO:0000269|PubMed:9847332}.; FUNCTION: (Microbial infection) Plays a role in the down-regulation of the 2-5A/RNASEL pathway during encephalomyocarditis virus (EMCV) and HIV-1 infections. {ECO:0000269|PubMed:9660177}. |
| P61247 | RPS3A | S236 | ochoa | Small ribosomal subunit protein eS1 (40S ribosomal protein S3a) (v-fos transformation effector protein) (Fte-1) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). May play a role during erythropoiesis through regulation of transcription factor DDIT3 (By similarity). {ECO:0000255|HAMAP-Rule:MF_03122, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P61513 | RPL37A | S59 | ochoa | Large ribosomal subunit protein eL43 (60S ribosomal protein L37a) | Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| P61601 | NCALD | S175 | ochoa | Neurocalcin-delta | May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions. |
| P61604 | HSPE1 | S53 | ochoa | 10 kDa heat shock protein, mitochondrial (Hsp10) (10 kDa chaperonin) (Chaperonin 10) (CPN10) (Early-pregnancy factor) (EPF) (Heat shock protein family E member 1) | Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131, PubMed:7912672). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000269|PubMed:7912672, ECO:0000305|PubMed:25918392}. |
| P61962 | DCAF7 | S200 | psp | DDB1- and CUL4-associated factor 7 (WD repeat-containing protein 68) (WD repeat-containing protein An11 homolog) | Involved in craniofacial development. Acts upstream of the EDN1 pathway and is required for formation of the upper jaw equivalent, the palatoquadrate. The activity required for EDN1 pathway function differs between the first and second arches (By similarity). Associates with DIAPH1 and controls GLI1 transcriptional activity. Could be involved in normal and disease skin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. {ECO:0000250, ECO:0000269|PubMed:16887337, ECO:0000269|PubMed:16949367}. |
| P61978 | HNRNPK | S141 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P61978 | HNRNPK | S401 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P62136 | PPP1CA | S22 | ochoa | Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PP-1A) (EC 3.1.3.16) | Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets (PubMed:28216226, PubMed:30158517, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39603239, PubMed:39603240). Protein phosphatase 1 (PP1) is essential for cell division, transcription elongation, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39603239, PubMed:39603240). Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Catalytic component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation: the PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex also regulates transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription (PubMed:31677974). PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at 'Ser-5' of the CTD, promoting RNA polymerase II degradation (PubMed:33264625). PNUTS-PP1 also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (PubMed:20516061). Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage (PubMed:17283141). Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development (By similarity). In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:21712997). May dephosphorylate CSNK1D and CSNK1E (PubMed:21712997). Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323). Together with PPP1CC (PP1-gamma subunit), dephosphorylates IFIH1/MDA5 and RIG-I leading to their activation and a functional innate immune response (PubMed:23499489). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670). {ECO:0000250|UniProtKB:P62137, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:30158517, ECO:0000269|PubMed:31677974, ECO:0000269|PubMed:33264625, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35830882, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670, ECO:0000269|PubMed:39603239, ECO:0000269|PubMed:39603240}.; FUNCTION: (Microbial infection) Necessary for alphaviruses replication. {ECO:0000269|PubMed:29769351}. |
| P62701 | RPS4X | S204 | ochoa | Small ribosomal subunit protein eS4, X isoform (40S ribosomal protein S4) (SCR10) (Single copy abundant mRNA protein) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P62807 | H2BC4 | S57 | ochoa | Histone H2B type 1-C/E/F/G/I (Histone H2B.1 A) (Histone H2B.a) (H2B/a) (Histone H2B.g) (H2B/g) (Histone H2B.h) (H2B/h) (Histone H2B.k) (H2B/k) (Histone H2B.l) (H2B/l) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.; FUNCTION: Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid. |
| P62910 | RPL32 | S62 | ochoa | Large ribosomal subunit protein eL32 (60S ribosomal protein L32) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| P62937 | PPIA | S110 | ochoa | Peptidyl-prolyl cis-trans isomerase A (PPIase A) (EC 5.2.1.8) (Cyclophilin A) (Cyclosporin A-binding protein) (Rotamase A) [Cleaved into: Peptidyl-prolyl cis-trans isomerase A, N-terminally processed] | Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.; FUNCTION: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.; FUNCTION: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}. |
| P68363 | TUBA1B | S379 | ochoa | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P68366 | TUBA4A | S379 | ochoa | Tubulin alpha-4A chain (EC 3.6.5.-) (Alpha-tubulin 1) (Testis-specific alpha-tubulin) (Tubulin H2-alpha) (Tubulin alpha-1 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P78312 | FAM193A | S287 | ochoa | Protein FAM193A (Protein IT14) | None |
| P78347 | GTF2I | S710 | ochoa | General transcription factor II-I (GTFII-I) (TFII-I) (Bruton tyrosine kinase-associated protein 135) (BAP-135) (BTK-associated protein 135) (SRF-Phox1-interacting protein) (SPIN) (Williams-Beuren syndrome chromosomal region 6 protein) | Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C-FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box. Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation. {ECO:0000269|PubMed:10373551, ECO:0000269|PubMed:11373296, ECO:0000269|PubMed:16738337}. |
| P78352 | DLG4 | S418 | ochoa | Disks large homolog 4 (Postsynaptic density protein 95) (PSD-95) (Synapse-associated protein 90) (SAP-90) (SAP90) | Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723). {ECO:0000250|UniProtKB:Q62108, ECO:0000269|PubMed:26334723}. |
| P78352 | DLG4 | S422 | ochoa | Disks large homolog 4 (Postsynaptic density protein 95) (PSD-95) (Synapse-associated protein 90) (SAP-90) (SAP90) | Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723). {ECO:0000250|UniProtKB:Q62108, ECO:0000269|PubMed:26334723}. |
| P78352 | DLG4 | S561 | psp | Disks large homolog 4 (Postsynaptic density protein 95) (PSD-95) (Synapse-associated protein 90) (SAP-90) (SAP90) | Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723). {ECO:0000250|UniProtKB:Q62108, ECO:0000269|PubMed:26334723}. |
| P78362 | SRPK2 | S608 | ochoa | SRSF protein kinase 2 (EC 2.7.11.1) (SFRS protein kinase 2) (Serine/arginine-rich protein-specific kinase 2) (SR-protein-specific kinase 2) [Cleaved into: SRSF protein kinase 2 N-terminal; SRSF protein kinase 2 C-terminal] | Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing (PubMed:18559500, PubMed:21056976, PubMed:9472028). Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression (PubMed:19592491). This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression (PubMed:21205200). Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation (PubMed:18559500). Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28 (PubMed:18425142). Probably by phosphorylating DDX23, leads to the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:28076779). Can mediate hepatitis B virus (HBV) core protein phosphorylation (PubMed:12134018). Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles (PubMed:16122776). {ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:18425142, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21056976, ECO:0000269|PubMed:21205200, ECO:0000269|PubMed:28076779, ECO:0000269|PubMed:9472028}. |
| P78371 | CCT2 | S54 | psp | T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P78371 | CCT2 | S254 | ochoa | T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P78504 | JAG1 | S1101 | ochoa | Protein jagged-1 (Jagged1) (hJ1) (CD antigen CD339) | Ligand for multiple Notch receptors and involved in the mediation of Notch signaling (PubMed:18660822, PubMed:20437614). May be involved in cell-fate decisions during hematopoiesis (PubMed:9462510). Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). Enhances fibroblast growth factor-induced angiogenesis (in vitro). {ECO:0000250, ECO:0000269|PubMed:18660822, ECO:0000269|PubMed:20437614, ECO:0000269|PubMed:9462510}. |
| P78527 | PRKDC | S2624 | ochoa|psp | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P78559 | MAP1A | S2686 | ochoa | Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Cleaved into: MAP1A heavy chain; MAP1 light chain LC2] | Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. |
| P84074 | HPCA | S175 | ochoa | Neuron-specific calcium-binding protein hippocalcin (Calcium-binding protein BDR-2) | Calcium-binding protein that may play a role in the regulation of voltage-dependent calcium channels (PubMed:28398555). May also play a role in cyclic-nucleotide-mediated signaling through the regulation of adenylate and guanylate cyclases (By similarity). {ECO:0000250|UniProtKB:P84076, ECO:0000269|PubMed:28398555}. |
| P85037 | FOXK1 | S455 | ochoa | Forkhead box protein K1 (Myocyte nuclear factor) (MNF) | Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:17670796). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity). Represses myogenic differentiation by inhibiting MEFC activity (By similarity). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK1-bound genes (PubMed:24634419, PubMed:30664650). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164, ECO:0000269|PubMed:30664650}. |
| Q00325 | SLC25A3 | S297 | ochoa | Solute carrier family 25 member 3 (Phosphate carrier protein, mitochondrial) (Phosphate transport protein) (PTP) | Inorganic ion transporter that transports phosphate or copper ions across the mitochondrial inner membrane into the matrix compartment (By similarity) (PubMed:17273968, PubMed:29237729). Mediates proton-coupled symport of phosphate ions necessary for mitochondrial oxidative phosphorylation of ADP to ATP (By similarity) (PubMed:17273968). Transports copper ions probably in the form of anionic copper(I) complexes to maintain mitochondrial matrix copper pool and to supply copper for cytochrome C oxidase complex assembly (PubMed:29237729). May also play a role in regulation of the mitochondrial permeability transition pore (mPTP) (By similarity). {ECO:0000250|UniProtKB:P12234, ECO:0000250|UniProtKB:P16036, ECO:0000269|PubMed:17273968, ECO:0000269|PubMed:29237729}. |
| Q00537 | CDK17 | S80 | ochoa | Cyclin-dependent kinase 17 (EC 2.7.11.22) (Cell division protein kinase 17) (PCTAIRE-motif protein kinase 2) (Serine/threonine-protein kinase PCTAIRE-2) | May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}. |
| Q00537 | CDK17 | S92 | ochoa | Cyclin-dependent kinase 17 (EC 2.7.11.22) (Cell division protein kinase 17) (PCTAIRE-motif protein kinase 2) (Serine/threonine-protein kinase PCTAIRE-2) | May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}. |
| Q00537 | CDK17 | S105 | ochoa | Cyclin-dependent kinase 17 (EC 2.7.11.22) (Cell division protein kinase 17) (PCTAIRE-motif protein kinase 2) (Serine/threonine-protein kinase PCTAIRE-2) | May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}. |
| Q00577 | PURA | S182 | ochoa | Transcriptional activator protein Pur-alpha (Purine-rich single-stranded DNA-binding protein alpha) | This is a probable transcription activator that specifically binds the purine-rich single strand of the PUR element located upstream of the MYC gene (PubMed:1448097, PubMed:20976240). May play a role in the initiation of DNA replication and in recombination. {ECO:0000269|PubMed:1448097, ECO:0000269|PubMed:20976240}. |
| Q00587 | CDC42EP1 | S365 | ochoa | Cdc42 effector protein 1 (Binder of Rho GTPases 5) (Serum protein MSE55) | Probably involved in the organization of the actin cytoskeleton. Induced membrane extensions in fibroblasts. {ECO:0000269|PubMed:10430899}. |
| Q00978 | IRF9 | S283 | ochoa | Interferon regulatory factor 9 (IRF-9) (IFN-alpha-responsive transcription factor subunit) (ISGF3 p48 subunit) (Interferon-stimulated gene factor 3 gamma) (ISGF-3 gamma) (Transcriptional regulator ISGF3 subunit gamma) | Transcription factor that plays an essential role in anti-viral immunity. It mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. {ECO:0000269|PubMed:30143481}. |
| Q01094 | E2F1 | S364 | psp | Transcription factor E2F1 (E2F-1) (PBR3) (Retinoblastoma-associated protein 1) (RBAP-1) (Retinoblastoma-binding protein 3) (RBBP-3) (pRB-binding protein E2F-1) | Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication (PubMed:10675335, PubMed:12717439, PubMed:17050006, PubMed:17704056, PubMed:18625225, PubMed:28992046). The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase (PubMed:10675335, PubMed:12717439, PubMed:17704056). E2F1 binds preferentially RB1 in a cell-cycle dependent manner (PubMed:10675335, PubMed:12717439, PubMed:17704056). It can mediate both cell proliferation and TP53/p53-dependent apoptosis (PubMed:8170954). Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812). Directly activates transcription of PEG10 (PubMed:17050006, PubMed:18625225, PubMed:28992046). Positively regulates transcription of RRP1B (PubMed:20040599). {ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:18625225, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:8170954}. |
| Q01201 | RELB | S254 | ochoa | Transcription factor RelB (I-Rel) | NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function (PubMed:26385063). {ECO:0000269|PubMed:1732739, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:26385063, ECO:0000269|PubMed:7925301, ECO:0000269|PubMed:8441398}. |
| Q01538 | MYT1 | S94 | ochoa | Myelin transcription factor 1 (MyT1) (Myelin transcription factor I) (MyTI) (PLPB1) (Proteolipid protein-binding protein) | Binds to the promoter region of genes encoding proteolipid proteins of the central nervous system. May play a role in the development of neurons and oligodendroglia in the CNS. May regulate a critical transition point in oligodendrocyte lineage development by modulating oligodendrocyte progenitor proliferation relative to terminal differentiation and up-regulation of myelin gene transcription. {ECO:0000269|PubMed:14962745}. |
| Q01804 | OTUD4 | S905 | ochoa | OTU domain-containing protein 4 (EC 3.4.19.12) (HIV-1-induced protein HIN-1) | Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}. |
| Q01804 | OTUD4 | S1049 | ochoa | OTU domain-containing protein 4 (EC 3.4.19.12) (HIV-1-induced protein HIN-1) | Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}. |
| Q01831 | XPC | S104 | ochoa | DNA repair protein complementing XP-C cells (Xeroderma pigmentosum group C-complementing protein) (p125) | Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex (PubMed:10734143, PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19609301, PubMed:19941824, PubMed:20028083, PubMed:20649465, PubMed:20798892, PubMed:9734359). Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides (PubMed:10734143, PubMed:19609301, PubMed:20649465). This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity (PubMed:10734143, PubMed:19609301, PubMed:20649465). The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). The orientation of XPC complex binding appears to be crucial for inducing a productive NER (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair (PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892, PubMed:9734359). In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts (PubMed:20028083). XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1 (PubMed:20028083). {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:10873465, ECO:0000269|PubMed:12509299, ECO:0000269|PubMed:12547395, ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:19941824, ECO:0000269|PubMed:20028083, ECO:0000269|PubMed:20649465, ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:9734359}.; FUNCTION: In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT) (PubMed:29973595, PubMed:31527837). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes (PubMed:31527837). {ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837}. |
| Q01968 | OCRL | S716 | ochoa | Inositol polyphosphate 5-phosphatase OCRL (EC 3.1.3.36) (EC 3.1.3.56) (Inositol polyphosphate 5-phosphatase OCRL-1) (OCRL-1) (Lowe oculocerebrorenal syndrome protein) (Phosphatidylinositol 3,4,5-triphosphate 5-phosphatase) (EC 3.1.3.86) | Catalyzes the hydrolysis of the 5-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic activity towards PtdIns(4,5)P2 (PubMed:10764818, PubMed:15474001, PubMed:7761412, PubMed:9430698). Able also to hydrolyze the 5-phosphate of inositol 1,4,5-trisphosphate and of inositol 1,3,4,5-tetrakisphosphate (PubMed:25869668, PubMed:7761412). Regulates traffic in the endosomal pathway by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with endosomes (PubMed:21971085). Involved in primary cilia assembly (PubMed:22228094, PubMed:22543976). Acts as a regulator of phagocytosis, hydrolyzing PtdIns(4,5)P2 to promote phagosome closure, through attenuation of PI3K signaling (PubMed:22072788). {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:15474001, ECO:0000269|PubMed:21971085, ECO:0000269|PubMed:22072788, ECO:0000269|PubMed:22228094, ECO:0000269|PubMed:22543976, ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:7761412, ECO:0000269|PubMed:9430698}. |
| Q01974 | ROR2 | S576 | ochoa | Tyrosine-protein kinase transmembrane receptor ROR2 (EC 2.7.10.1) (Neurotrophic tyrosine kinase, receptor-related 2) | Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development (By similarity). Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation (PubMed:17717073). In contrast, has also been shown to have very little tyrosine kinase activity in vitro. May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443). {ECO:0000250|UniProtKB:Q9Z138, ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:25029443}. |
| Q01995 | TAGLN | S135 | ochoa | Transgelin (22 kDa actin-binding protein) (Protein WS3-10) (Smooth muscle protein 22-alpha) (SM22-alpha) | Actin cross-linking/gelling protein (By similarity). Involved in calcium interactions and contractile properties of the cell that may contribute to replicative senescence. {ECO:0000250}. |
| Q02156 | PRKCE | S234 | psp | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
| Q02487 | DSC2 | S868 | ochoa | Desmocollin-2 (Cadherin family member 2) (Desmocollin-3) (Desmosomal glycoprotein II) (Desmosomal glycoprotein III) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:33596089). Promotes timely incorporation of DSG2 into desmosome intercellular junctions and promotes interaction of desmosome cell junctions with intermediate filament cytokeratin, via modulation of DSP phosphorylation (PubMed:33596089). Plays an important role in desmosome-mediated maintenance of intestinal epithelial cell intercellular adhesion strength and barrier function (PubMed:33596089). Positively regulates wound healing of intestinal mucosa via promotion of epithelial cell migration, and also plays a role in mechanotransduction of force between intestinal epithelial cells and extracellular matrix (PubMed:31967937). May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. May promote p38MAPK signaling activation that facilitates keratinocyte migration (By similarity). {ECO:0000250|UniProtKB:P55292, ECO:0000269|PubMed:31967937, ECO:0000269|PubMed:33596089}. |
| Q02539 | H1-1 | S107 | ochoa | Histone H1.1 (Histone H1a) | Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}. |
| Q02790 | FKBP4 | S336 | ochoa | Peptidyl-prolyl cis-trans isomerase FKBP4 (PPIase FKBP4) (EC 5.2.1.8) (51 kDa FK506-binding protein) (FKBP51) (52 kDa FK506-binding protein) (52 kDa FKBP) (FKBP-52) (59 kDa immunophilin) (p59) (FK506-binding protein 4) (FKBP-4) (FKBP59) (HSP-binding immunophilin) (HBI) (Immunophilin FKBP52) (Rotamase) [Cleaved into: Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed] | Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Also acts as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}. |
| Q02952 | AKAP12 | S514 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q02952 | AKAP12 | S1507 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q03001 | DST | S2239 | ochoa | Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) | Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. |
| Q03001 | DST | S2502 | ochoa | Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) | Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. |
| Q03001 | DST | S2553 | ochoa | Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) | Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. |
| Q03164 | KMT2A | S2350 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q03164 | KMT2A | S2611 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q04206 | RELA | S205 | psp | Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148}. |
| Q04721 | NOTCH2 | S1855 | ochoa | Neurogenic locus notch homolog protein 2 (Notch 2) (hN2) [Cleaved into: Notch 2 extracellular truncation (N2ECD); Notch 2 intracellular domain (N2ICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus (PubMed:21378985, PubMed:21378989). Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737). {ECO:0000250|UniProtKB:O35516, ECO:0000269|PubMed:21378985, ECO:0000269|PubMed:21378989, ECO:0000269|PubMed:25985737, ECO:0000269|PubMed:29149593}. |
| Q04864 | REL | S34 | ochoa | Proto-oncogene c-Rel | Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator. |
| Q05086 | UBE3A | S93 | ochoa | Ubiquitin-protein ligase E3A (EC 2.3.2.26) (E6AP ubiquitin-protein ligase) (HECT-type ubiquitin transferase E3A) (Human papillomavirus E6-associated protein) (Oncogenic protein-associated protein E6-AP) (Renal carcinoma antigen NY-REN-54) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:10373495, PubMed:16772533, PubMed:19204938, PubMed:19233847, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24273172, PubMed:24728990, PubMed:30020076). Several substrates have been identified including the BMAL1, ARC, LAMTOR1, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B (PubMed:10373495, PubMed:19204938, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24728990, PubMed:30020076). Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins (PubMed:19233847). Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component BMAL1, leading to its proteasomal degradation (PubMed:24728990). Acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation (PubMed:16772533). Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (By similarity). Required for synaptic remodeling in neurons by mediating ubiquitination and degradation of LAMTOR1, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (By similarity). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533). {ECO:0000250|UniProtKB:O08759, ECO:0000269|PubMed:10373495, ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:19204938, ECO:0000269|PubMed:19233847, ECO:0000269|PubMed:19325566, ECO:0000269|PubMed:19591933, ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:24273172, ECO:0000269|PubMed:24728990, ECO:0000269|PubMed:30020076}.; FUNCTION: (Microbial infection) Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses. {ECO:0000269|PubMed:8380895}. |
| Q05193 | DNM1 | S347 | psp | Dynamin-1 (EC 3.6.5.5) (Dynamin) (Dynamin I) | Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission and participates in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis as well as rapid endocytosis (RE) (PubMed:15703209, PubMed:20428113, PubMed:29668686, PubMed:8101525, PubMed:8910402, PubMed:9362482). Associates to the membrane, through lipid binding, and self-assembles into rings and stacks of interconnected rings through oligomerization to form a helical polymer around the vesicle membrane leading to constriction of invaginated coated pits around their necks (PubMed:30069048, PubMed:7877694, PubMed:9922133). Self-assembly of the helical polymer induces membrane tubules narrowing until the polymer reaches a length sufficient to trigger GTP hydrolysis (PubMed:19084269). Depending on the curvature imposed on the tubules, membrane detachment from the helical polymer upon GTP hydrolysis can cause spontaneous hemifission followed by complete fission (PubMed:19084269). May play a role in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells through its activation by dephosphorylation via the signaling downstream of EGFR (PubMed:29668686). Controls vesicle size at a step before fission, during formation of membrane pits, at hippocampal synapses (By similarity). Controls plastic adaptation of the synaptic vesicle recycling machinery to high levels of activity (By similarity). Mediates rapid endocytosis (RE), a Ca(2+)-dependent and clathrin- and K(+)-independent process in chromaffin cells (By similarity). Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP (By similarity). Through its interaction with DNAJC6, acts during the early steps of clathrin-coated vesicle (CCV) formation (PubMed:12791276). {ECO:0000250|UniProtKB:P39053, ECO:0000250|UniProtKB:Q08DF4, ECO:0000269|PubMed:12791276, ECO:0000269|PubMed:15703209, ECO:0000269|PubMed:19084269, ECO:0000269|PubMed:20428113, ECO:0000269|PubMed:29668686, ECO:0000269|PubMed:30069048, ECO:0000269|PubMed:7877694, ECO:0000269|PubMed:8101525, ECO:0000269|PubMed:8910402, ECO:0000269|PubMed:9362482, ECO:0000269|PubMed:9922133}. |
| Q05397 | PTK2 | S850 | ochoa | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| Q05655 | PRKCD | S359 | psp | Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}. |
| Q06187 | BTK | S55 | ochoa | Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) | Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}. |
| Q06210 | GFPT1 | S235 | psp | Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 (EC 2.6.1.16) (D-fructose-6-phosphate amidotransferase 1) (Glutamine:fructose-6-phosphate amidotransferase 1) (GFAT 1) (GFAT1) (Hexosephosphate aminotransferase 1) | Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (PubMed:26887390). {ECO:0000250|UniProtKB:P47856, ECO:0000269|PubMed:26887390}. |
| Q06265 | EXOSC9 | S384 | ochoa | Exosome complex component RRP45 (Autoantigen PM/Scl 1) (Exosome component 9) (P75 polymyositis-scleroderma overlap syndrome-associated autoantigen) (Polymyositis/scleroderma autoantigen 1) (Polymyositis/scleroderma autoantigen 75 kDa) (PM/Scl-75) | Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC9 binds to ARE-containing RNAs. {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:16455498, ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563}. |
| Q06546 | GABPA | S62 | ochoa | GA-binding protein alpha chain (GABP subunit alpha) (Nuclear respiratory factor 2 subunit alpha) (Transcription factor E4TF1-60) | Transcription factor capable of interacting with purine rich repeats (GA repeats). Positively regulates transcription of transcriptional repressor RHIT/ZNF205 (PubMed:22306510). {ECO:0000269|PubMed:22306510}.; FUNCTION: (Microbial infection) Necessary for the expression of the Adenovirus E4 gene. |
| Q06587 | RING1 | S163 | ochoa | E3 ubiquitin-protein ligase RING1 (EC 2.3.2.27) (Polycomb complex protein RING1) (RING finger protein 1) (RING-type E3 ubiquitin transferase RING1) (Really interesting new gene 1 protein) | Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity. {ECO:0000269|PubMed:16359901}. |
| Q07157 | TJP1 | S241 | ochoa | Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}. |
| Q07157 | TJP1 | S828 | ochoa | Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}. |
| Q07820 | MCL1 | S159 | ochoa|psp | Induced myeloid leukemia cell differentiation protein Mcl-1 (Bcl-2-like protein 3) (Bcl2-L-3) (Bcl-2-related protein EAT/mcl1) (mcl1/EAT) | Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. {ECO:0000269|PubMed:10766760, ECO:0000269|PubMed:16543145}. |
| Q07864 | POLE | S1317 | ochoa | DNA polymerase epsilon catalytic subunit A (EC 2.7.7.7) (3'-5' exodeoxyribonuclease) (EC 3.1.11.-) (DNA polymerase II subunit A) | Catalytic component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in chromosomal DNA replication (By similarity). Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199). Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374). {ECO:0000250|UniProtKB:P21951, ECO:0000269|PubMed:10801849, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:27573199}. |
| Q07864 | POLE | S2077 | ochoa | DNA polymerase epsilon catalytic subunit A (EC 2.7.7.7) (3'-5' exodeoxyribonuclease) (EC 3.1.11.-) (DNA polymerase II subunit A) | Catalytic component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in chromosomal DNA replication (By similarity). Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199). Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374). {ECO:0000250|UniProtKB:P21951, ECO:0000269|PubMed:10801849, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:27573199}. |
| Q07954 | LRP1 | S4517 | psp | Prolow-density lipoprotein receptor-related protein 1 (LRP-1) (Alpha-2-macroglobulin receptor) (A2MR) (Apolipoprotein E receptor) (APOER) (CD antigen CD91) [Cleaved into: Low-density lipoprotein receptor-related protein 1 85 kDa subunit (LRP-85); Low-density lipoprotein receptor-related protein 1 515 kDa subunit (LRP-515); Low-density lipoprotein receptor-related protein 1 intracellular domain (LRPICD)] | Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells (PubMed:11907044, PubMed:12713657). Required for early embryonic development (By similarity). Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Acts as an LRPAP1 alpha-2-macroglobulin receptor (PubMed:1702392, PubMed:26142438). Acts as TAU/MAPT receptor and controls the endocytosis of TAU/MAPT as well as its subsequent spread (PubMed:32296178). May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission (PubMed:12888553). Also acts as a receptor for IGFBP3 to mediate cell growth inhibition (PubMed:9252371). {ECO:0000250|UniProtKB:Q91ZX7, ECO:0000269|PubMed:11907044, ECO:0000269|PubMed:12713657, ECO:0000269|PubMed:12888553, ECO:0000269|PubMed:1702392, ECO:0000269|PubMed:26142438, ECO:0000269|PubMed:32296178, ECO:0000269|PubMed:9252371}.; FUNCTION: (Microbial infection) Functions as a receptor for Pseudomonas aeruginosa exotoxin A. {ECO:0000269|PubMed:1618748}. |
| Q07955 | SRSF1 | S133 | psp | Serine/arginine-rich splicing factor 1 (Alternative-splicing factor 1) (ASF-1) (Splicing factor, arginine/serine-rich 1) (pre-mRNA-splicing factor SF2, P33 subunit) | Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway. {ECO:0000269|PubMed:8139654}. |
| Q08211 | DHX9 | S130 | ochoa | ATP-dependent RNA helicase A (EC 3.6.4.13) (DEAH box protein 9) (DExH-box helicase 9) (Leukophysin) (LKP) (Nuclear DNA helicase II) (NDH II) (RNA helicase A) | Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:24990949, PubMed:25062910, PubMed:28221134, PubMed:9111062, PubMed:37467750). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:10198287, PubMed:9111062). Also binds to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11038348, PubMed:11149922, PubMed:11416126, PubMed:15355351, PubMed:28221134, PubMed:9323138, PubMed:9662397). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Also acts as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:10924507, PubMed:11402034, PubMed:9162007). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588). {ECO:0000250|UniProtKB:O70133, ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:11038348, ECO:0000269|PubMed:11149922, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11416126, ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:12711669, ECO:0000269|PubMed:15355351, ECO:0000269|PubMed:1537828, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20669935, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:21561811, ECO:0000269|PubMed:22190748, ECO:0000269|PubMed:24049074, ECO:0000269|PubMed:24990949, ECO:0000269|PubMed:25062910, ECO:0000269|PubMed:28221134, ECO:0000269|PubMed:28355180, ECO:0000269|PubMed:28636595, ECO:0000269|PubMed:37467750, ECO:0000269|PubMed:9111062, ECO:0000269|PubMed:9162007, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9662397}.; FUNCTION: (Microbial infection) Plays a role in HIV-1 replication and virion infectivity (PubMed:11096080, PubMed:19229320, PubMed:25149208, PubMed:27107641). Enhances HIV-1 transcription by facilitating the binding of RNA polymerase II holoenzyme to the proviral DNA (PubMed:11096080, PubMed:25149208). Binds (via DRBM domain 2) to the HIV-1 TAR RNA and stimulates HIV-1 transcription of transactivation response element (TAR)-containing mRNAs (PubMed:11096080, PubMed:9892698). Involved also in HIV-1 mRNA splicing and transport (PubMed:25149208). Positively regulates HIV-1 gag mRNA translation, through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Binds (via DRBM domains) to a HIV-1 double-stranded RNA region of the primer binding site (PBS)-segment of the 5'-UTR, and hence stimulates DHX9 incorporation into virions and virion infectivity (PubMed:27107641). Also plays a role as a cytosolic viral MyD88-dependent DNA and RNA sensors in plasmacytoid dendritic cells (pDCs), and hence induce antiviral innate immune responses (PubMed:20696886, PubMed:21957149). Binds (via the OB-fold region) to viral single-stranded DNA unmethylated C-phosphate-G (CpG) oligonucleotide (PubMed:20696886). {ECO:0000269|PubMed:11096080, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:20696886, ECO:0000269|PubMed:21957149, ECO:0000269|PubMed:25149208, ECO:0000269|PubMed:27107641, ECO:0000269|PubMed:9892698}. |
| Q08357 | SLC20A2 | S321 | ochoa | Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. |
| Q08357 | SLC20A2 | S407 | ochoa | Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. |
| Q08378 | GOLGA3 | S115 | ochoa | Golgin subfamily A member 3 (Golgi complex-associated protein of 170 kDa) (GCP170) (Golgin-160) | Golgi auto-antigen; probably involved in maintaining Golgi structure. |
| Q08379 | GOLGA2 | S981 | ochoa | Golgin subfamily A member 2 (130 kDa cis-Golgi matrix protein) (GM130) (GM130 autoantigen) (Golgin-95) | Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane (Probable) (PubMed:16489344). Required for normal protein transport from the endoplasmic reticulum to the Golgi apparatus and the cell membrane (By similarity). Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401). {ECO:0000250|UniProtKB:Q62839, ECO:0000250|UniProtKB:Q921M4, ECO:0000269|PubMed:16489344, ECO:0000269|PubMed:17314401, ECO:0000269|PubMed:18045989, ECO:0000269|PubMed:19109421, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:26165940, ECO:0000305|PubMed:26363069}. |
| Q08499 | PDE4D | S596 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:9371713}. |
| Q08999 | RBL2 | S639 | ochoa|psp | Retinoblastoma-like protein 2 (130 kDa retinoblastoma-associated protein) (p130) (Retinoblastoma-related protein 2) (RBR-2) (pRb2) | Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor. |
| Q09666 | AHNAK | S407 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S466 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S539 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S559 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S691 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S2150 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S3509 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S3724 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S4425 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5298 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5418 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5530 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5593 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q0JRZ9 | FCHO2 | S682 | ochoa | F-BAR domain only protein 2 | Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2-dependent endocytosis of the transferrin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor. {ECO:0000269|PubMed:17540576, ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:21762413, ECO:0000269|PubMed:22323290}. |
| Q0VF96 | CGNL1 | S349 | ochoa | Cingulin-like protein 1 (Junction-associated coiled-coil protein) (Paracingulin) | May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons. {ECO:0000269|PubMed:22891260}. |
| Q10471 | GALNT2 | S536 | ochoa | Polypeptide N-acetylgalactosaminyltransferase 2 (EC 2.4.1.41) (Polypeptide GalNAc transferase 2) (GalNAc-T2) (pp-GaNTase 2) (Protein-UDP acetylgalactosaminyltransferase 2) (UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 2) [Cleaved into: Polypeptide N-acetylgalactosaminyltransferase 2 soluble form] | Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region. Involved in O-linked glycosylation of APOC-III, ANGPTL3 and PLTP. It participates in the regulation of HDL-C metabolism (PubMed:27508872, PubMed:32293671). {ECO:0000269|PubMed:12438318, ECO:0000269|PubMed:16207894, ECO:0000269|PubMed:16434399, ECO:0000269|PubMed:25939779, ECO:0000269|PubMed:27508872, ECO:0000269|PubMed:32293671, ECO:0000269|PubMed:7592619, ECO:0000269|PubMed:9295285}. |
| Q10570 | CPSF1 | S734 | ochoa | Cleavage and polyadenylation specificity factor subunit 1 (Cleavage and polyadenylation specificity factor 160 kDa subunit) (CPSF 160 kDa subunit) | Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction (PubMed:14749727). May play a role in eye morphogenesis and the development of retinal ganglion cell projections to the midbrain (By similarity). {ECO:0000250|UniProtKB:A0A0R4IC37, ECO:0000269|PubMed:14749727}. |
| Q12815 | TROAP | S222 | ochoa | Tastin (Trophinin-assisting protein) (Trophinin-associated protein) | Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation. |
| Q12815 | TROAP | S408 | ochoa | Tastin (Trophinin-assisting protein) (Trophinin-associated protein) | Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation. |
| Q12830 | BPTF | S1297 | ochoa | Nucleosome-remodeling factor subunit BPTF (Bromodomain and PHD finger-containing transcription factor) (Fetal Alz-50 clone 1 protein) (Fetal Alzheimer antigen) | Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:14609955, PubMed:28801535). The NURF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NURF-5 ISWI chromatin remodeling complex (PubMed:28801535). Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development (PubMed:14609955). Histone-binding protein which binds to H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of active genes (PubMed:16728976, PubMed:16728978). Binds to histone H3 tails dimethylated on 'Lys-4' (H3K4Me2) to a lesser extent (PubMed:16728976, PubMed:16728978, PubMed:18042461). May also regulate transcription through direct binding to DNA or transcription factors (PubMed:10575013). {ECO:0000269|PubMed:10575013, ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:16728976, ECO:0000269|PubMed:16728978, ECO:0000269|PubMed:18042461, ECO:0000269|PubMed:28801535}. |
| Q12846 | STX4 | S36 | ochoa | Syntaxin-4 (Renal carcinoma antigen NY-REN-31) | Plasma membrane t-SNARE that mediates docking of transport vesicles (By similarity). Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane (By similarity). In neurons, recruited at neurite tips to membrane domains rich in the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) which promotes neurite tip surface expression of the dopamine transporter SLC6A3/DAT by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity). Together with STXB3 and VAMP2, may also play a role in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes and in docking of synaptic vesicles at presynaptic active zones (By similarity). Required for normal hearing (PubMed:36355422). {ECO:0000250|UniProtKB:P70452, ECO:0000250|UniProtKB:Q08850, ECO:0000269|PubMed:36355422}. |
| Q12852 | MAP3K12 | S555 | ochoa | Mitogen-activated protein kinase kinase kinase 12 (EC 2.7.11.25) (Dual leucine zipper bearing kinase) (DLK) (Leucine-zipper protein kinase) (ZPK) (MAPK-upstream kinase) (MUK) (Mixed lineage kinase) | Part of a non-canonical MAPK signaling pathway (PubMed:28111074). Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074). May be an activator of the JNK/SAPK pathway. {ECO:0000269|PubMed:28111074}. |
| Q12873 | CHD3 | S308 | ochoa | Chromodomain-helicase-DNA-binding protein 3 (CHD-3) (EC 3.6.4.-) (ATP-dependent helicase CHD3) (Mi-2 autoantigen 240 kDa protein) (Mi2-alpha) (Zinc finger helicase) (hZFH) | ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA (PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666, PubMed:30397230, PubMed:9804427). Involved in transcriptional repression as part of the NuRD complex (PubMed:27068747). Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity (PubMed:17626165). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:27068747, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:30397230, ECO:0000269|PubMed:9804427}. |
| Q12879 | GRIN2A | S890 | ochoa | Glutamate receptor ionotropic, NMDA 2A (GluN2A) (Glutamate [NMDA] receptor subunit epsilon-1) (N-methyl D-aspartate receptor subtype 2A) (NMDAR2A) (NR2A) (hNR2A) | Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:20890276, PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:28242877, PubMed:36117210, PubMed:38538865, PubMed:8768735). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:27288002, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28182669, PubMed:29644724, PubMed:38307912, PubMed:8768735). NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761). Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte (By similarity). {ECO:0000250|UniProtKB:P35436, ECO:0000250|UniProtKB:P35438, ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23933818, ECO:0000269|PubMed:23933819, ECO:0000269|PubMed:23933820, ECO:0000269|PubMed:24504326, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27288002, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28182669, ECO:0000269|PubMed:28242877, ECO:0000269|PubMed:29644724, ECO:0000269|PubMed:36117210, ECO:0000269|PubMed:38307912, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:8768735}. |
| Q12882 | DPYD | S440 | ochoa | Dihydropyrimidine dehydrogenase [NADP(+)] (DHPDHase) (DPD) (EC 1.3.1.2) (Dihydrothymine dehydrogenase) (Dihydrouracil dehydrogenase) | Involved in pyrimidine base degradation (PubMed:1512248). Catalyzes the reduction of uracil and thymine (PubMed:1512248). Also involved the degradation of the chemotherapeutic drug 5-fluorouracil (PubMed:1512248). {ECO:0000269|PubMed:1512248}. |
| Q12888 | TP53BP1 | S566 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12923 | PTPN13 | S512 | ochoa | Tyrosine-protein phosphatase non-receptor type 13 (EC 3.1.3.48) (Fas-associated protein-tyrosine phosphatase 1) (FAP-1) (PTP-BAS) (Protein-tyrosine phosphatase 1E) (PTP-E1) (hPTPE1) (Protein-tyrosine phosphatase PTPL1) | Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}. |
| Q12931 | TRAP1 | S195 | ochoa | Heat shock protein 75 kDa, mitochondrial (HSP 75) (Heat shock protein family C member 5) (TNFR-associated protein 1) (Tumor necrosis factor type 1 receptor-associated protein) (TRAP-1) | Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. {ECO:0000269|PubMed:23525905, ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:23747254}. |
| Q12955 | ANK3 | S4181 | ochoa | Ankyrin-3 (ANK-3) (Ankyrin-G) | Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}. |
| Q12959 | DLG1 | S517 | ochoa | Disks large homolog 1 (Synapse-associated protein 97) (SAP-97) (SAP97) (hDlg) | Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). May also play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497). {ECO:0000250|UniProtKB:A0A8C0TYJ0, ECO:0000250|UniProtKB:Q811D0, ECO:0000269|PubMed:10656683, ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15263016, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:23676497}. |
| Q12965 | MYO1E | S980 | ochoa | Unconventional myosin-Ie (Myosin-Ic) (Unconventional myosin 1E) | Actin-based motor molecule with ATPase activity (PubMed:11940582, PubMed:36316095). Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. Binds to membranes containing anionic phospholipids via its tail domain. Involved in clathrin-mediated endocytosis and intracellular movement of clathrin-coated vesicles (PubMed:36316095). Required for normal morphology of the glomerular basement membrane, normal development of foot processes by kidney podocytes and normal kidney function. In dendritic cells, may control the movement of class II-containing cytoplasmic vesicles along the actin cytoskeleton by connecting them with the actin network via ARL14EP and ARL14. {ECO:0000269|PubMed:11940582, ECO:0000269|PubMed:17257598, ECO:0000269|PubMed:20860408, ECO:0000269|PubMed:36316095}. |
| Q12983 | BNIP3 | S144 | psp | BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 | Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway. {ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:22292033}. |
| Q13029 | PRDM2 | S1359 | ochoa | PR domain zinc finger protein 2 (EC 2.1.1.355) (GATA-3-binding protein G3B) (Lysine N-methyltransferase 8) (MTB-ZF) (MTE-binding protein) (PR domain-containing protein 2) (Retinoblastoma protein-interacting zinc finger protein) (Zinc finger protein RIZ) | S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates 'Lys-9' of histone H3. May function as a DNA-binding transcription factor. Binds to the macrophage-specific TPA-responsive element (MTE) of the HMOX1 (heme oxygenase 1) gene and may act as a transcriptional activator of this gene. {ECO:0000269|PubMed:14633678}. |
| Q13033 | STRN3 | S214 | ochoa | Striatin-3 (Cell cycle autoantigen SG2NA) (S/G2 antigen) | Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753, PubMed:30622739, PubMed:33633399). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (Probable). {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:33633399, ECO:0000305|PubMed:26876214}. |
| Q13043 | STK4 | S40 | psp | Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. |
| Q13085 | ACACA | S344 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13085 | ACACA | S835 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13136 | PPFIA1 | S530 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13148 | TARDBP | S254 | psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q13148 | TARDBP | S369 | psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q13177 | PAK2 | S381 | ochoa | Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. |
| Q13200 | PSMD2 | S363 | ochoa | 26S proteasome non-ATPase regulatory subunit 2 (26S proteasome regulatory subunit RPN1) (26S proteasome regulatory subunit S2) (26S proteasome subunit p97) (Protein 55.11) (Tumor necrosis factor type 1 receptor-associated protein 2) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}.; FUNCTION: Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1. |
| Q13201 | MMRN1 | S884 | ochoa | Multimerin-1 (EMILIN-4) (Elastin microfibril interface located protein 4) (Elastin microfibril interfacer 4) (Endothelial cell multimerin) [Cleaved into: Platelet glycoprotein Ia*; 155 kDa platelet multimerin (p-155) (p155)] | Carrier protein for platelet (but not plasma) factor V/Va. Plays a role in the storage and stabilization of factor V in platelets. Upon release following platelet activation, may limit platelet and plasma factor Va-dependent thrombin generation. Ligand for integrin alpha-IIb/beta-3 and integrin alpha-V/beta-3 on activated platelets, and may function as an extracellular matrix or adhesive protein. {ECO:0000269|PubMed:16363244, ECO:0000269|PubMed:19132231, ECO:0000269|PubMed:7629143}. |
| Q13228 | SELENBP1 | S111 | ochoa | Methanethiol oxidase (MTO) (EC 1.8.3.4) (56 kDa selenium-binding protein) (SBP56) (SP56) (Selenium-binding protein 1) | Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria (PubMed:29255262). Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity). {ECO:0000250|UniProtKB:Q8VIF7, ECO:0000269|PubMed:29255262}. |
| Q13242 | SRSF9 | S123 | ochoa | Serine/arginine-rich splicing factor 9 (Pre-mRNA-splicing factor SRp30C) (Splicing factor, arginine/serine-rich 9) | Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:10196175, ECO:0000269|PubMed:11875052, ECO:0000269|PubMed:12024014, ECO:0000269|PubMed:12604611, ECO:0000269|PubMed:15009090, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:15695522, ECO:0000269|PubMed:7556075}. |
| Q13263 | TRIM28 | S140 | ochoa | Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) | Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}. |
| Q13263 | TRIM28 | S501 | ochoa|psp | Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) | Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}. |
| Q13263 | TRIM28 | S512 | ochoa | Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) | Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}. |
| Q13283 | G3BP1 | S119 | ochoa | Ras GTPase-activating protein-binding protein 1 (G3BP-1) (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent DNA helicase VIII) (hDH VIII) (GAP SH3 domain-binding protein 1) | Protein involved in various processes, such as stress granule formation and innate immunity (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:30510222, PubMed:30804210). Plays an essential role in stress granule formation (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:35977029, PubMed:36183834, PubMed:36279435, PubMed:36692217, PubMed:37379838). Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:27022092, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:36279435, PubMed:37379838). Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations (PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:36279435, PubMed:36692217). Also acts as an ATP- and magnesium-dependent helicase: unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency (PubMed:9889278). Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA (PubMed:9889278). Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends (PubMed:9889278). Plays an essential role in innate immunity by promoting CGAS and RIGI activity (PubMed:30510222, PubMed:30804210). Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS (PubMed:30510222). Triggers the condensation of cGAS, a process probably linked to the formation of membrane-less organelles (PubMed:34779554). Also enhances RIGI-induced type I interferon production probably by helping RIGI at sensing pathogenic RNA (PubMed:30804210). May also act as a phosphorylation-dependent sequence-specific endoribonuclease in vitro: Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:12642610, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:23279204, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:30510222, ECO:0000269|PubMed:30804210, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:34779554, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:36183834, ECO:0000269|PubMed:36279435, ECO:0000269|PubMed:36692217, ECO:0000269|PubMed:37379838, ECO:0000269|PubMed:9889278}. |
| Q13315 | ATM | S1270 | psp | Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated) | Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217). May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, ECO:0000269|PubMed:9843217}. |
| Q13393 | PLD1 | S499 | ochoa | Phospholipase D1 (PLD 1) (hPLD1) (EC 3.1.4.4) (Choline phosphatase 1) (Phosphatidylcholine-hydrolyzing phospholipase D1) | Function as phospholipase selective for phosphatidylcholine (PubMed:25936805, PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). {ECO:0000250|UniProtKB:Q9Z280, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:8530346, ECO:0000269|PubMed:9582313}. |
| Q13409 | DYNC1I2 | S101 | ochoa | Cytoplasmic dynein 1 intermediate chain 2 (Cytoplasmic dynein intermediate chain 2) (Dynein intermediate chain 2, cytosolic) (DH IC-2) | Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (PubMed:31079899). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (PubMed:31079899). The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1 (By similarity). Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes (By similarity). {ECO:0000250|UniProtKB:Q62871, ECO:0000269|PubMed:31079899}. |
| Q13409 | DYNC1I2 | S111 | ochoa | Cytoplasmic dynein 1 intermediate chain 2 (Cytoplasmic dynein intermediate chain 2) (Dynein intermediate chain 2, cytosolic) (DH IC-2) | Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (PubMed:31079899). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (PubMed:31079899). The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1 (By similarity). Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes (By similarity). {ECO:0000250|UniProtKB:Q62871, ECO:0000269|PubMed:31079899}. |
| Q13439 | GOLGA4 | S118 | ochoa | Golgin subfamily A member 4 (256 kDa golgin) (Golgin-245) (Protein 72.1) (Trans-Golgi p230) | Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking (PubMed:29084197). {ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:29084197}. |
| Q13469 | NFATC2 | S704 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 2 (NF-ATc2) (NFATc2) (NFAT pre-existing subunit) (NF-ATp) (T-cell transcription factor NFAT1) | Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF (PubMed:15790681). Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway (PubMed:21871017). Is involved in the negative regulation of chondrogenesis (PubMed:35789258). Recruited by AKAP5 to ORAI1 pore-forming subunit of CRAC channels in Ca(2+) signaling microdomains where store-operated Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT-dependent transcriptional responses. {ECO:0000250|UniProtKB:Q60591, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:21871017, ECO:0000269|PubMed:35789258}. |
| Q13492 | PICALM | S20 | ochoa | Phosphatidylinositol-binding clathrin assembly protein (Clathrin assembly lymphoid myeloid leukemia protein) | Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly (PubMed:10436022, PubMed:16262731, PubMed:27574975). Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature (PubMed:25898166). In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 (PubMed:21808019, PubMed:22118466, PubMed:23741335). In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors (PubMed:25241929). Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF) (PubMed:24067654, PubMed:25241929). {ECO:0000269|PubMed:10436022, ECO:0000269|PubMed:16262731, ECO:0000269|PubMed:21808019, ECO:0000269|PubMed:22118466, ECO:0000269|PubMed:23741335, ECO:0000269|PubMed:24067654, ECO:0000269|PubMed:25241929, ECO:0000269|PubMed:25898166, ECO:0000269|PubMed:27574975}. |
| Q13501 | SQSTM1 | S318 | ochoa | Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) | Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}. |
| Q13523 | PRP4K | S837 | ochoa | Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) | Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}. |
| Q13546 | RIPK1 | S389 | ochoa|psp | Receptor-interacting serine/threonine-protein kinase 1 (EC 2.7.11.1) (Cell death protein RIP) (Receptor-interacting protein 1) (RIP-1) | Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:17703191, PubMed:24144979, PubMed:31827280, PubMed:31827281, PubMed:32657447, PubMed:35831301). Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (By similarity). Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (By similarity). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity). In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:15310755, PubMed:17389591). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity). {ECO:0000250|UniProtKB:Q60855, ECO:0000269|PubMed:11101870, ECO:0000269|PubMed:15310755, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:17703191, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513, ECO:0000269|PubMed:24144979, ECO:0000269|PubMed:29440439, ECO:0000269|PubMed:30988283, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32657447, ECO:0000269|PubMed:35831301}. |
| Q13555 | CAMK2G | S311 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit gamma (CaM kinase II subunit gamma) (CaMK-II subunit gamma) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q923T9, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:30184290}. |
| Q13586 | STIM1 | S512 | ochoa|psp | Stromal interaction molecule 1 | Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19182790, PubMed:19249086, PubMed:19622606, PubMed:19706554, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:25326555, PubMed:26322679, PubMed:28219928, PubMed:32415068). Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates CRAC channel pore-forming subunits ORA1, ORA2 and ORAI3 to generate sustained and oscillatory Ca(2+) entry (PubMed:16208375, PubMed:16537481, PubMed:32415068). Involved in enamel formation (PubMed:24621671). {ECO:0000269|PubMed:15866891, ECO:0000269|PubMed:16005298, ECO:0000269|PubMed:16208375, ECO:0000269|PubMed:16537481, ECO:0000269|PubMed:16733527, ECO:0000269|PubMed:16766533, ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:18854159, ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:22464749, ECO:0000269|PubMed:24069340, ECO:0000269|PubMed:24351972, ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:24621671, ECO:0000269|PubMed:25326555, ECO:0000269|PubMed:26322679, ECO:0000269|PubMed:28219928, ECO:0000269|PubMed:32415068}. |
| Q13596 | SNX1 | S32 | ochoa | Sorting nexin-1 | Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:12198132). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:19816406, PubMed:23085988). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin stxB. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi (PubMed:12198132, PubMed:15498486, PubMed:17101778, PubMed:17550970, PubMed:18088323, PubMed:21040701). Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R (PubMed:16407403, PubMed:20070609). Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901). Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking (PubMed:23152498). {ECO:0000269|PubMed:12198132, ECO:0000269|PubMed:15498486, ECO:0000269|PubMed:16407403, ECO:0000269|PubMed:17101778, ECO:0000269|PubMed:17550970, ECO:0000269|PubMed:18088323, ECO:0000269|PubMed:19816406, ECO:0000269|PubMed:20070609, ECO:0000269|PubMed:20604901, ECO:0000269|PubMed:21040701, ECO:0000269|PubMed:23085988, ECO:0000269|PubMed:23152498, ECO:0000303|PubMed:15498486}. |
| Q13618 | CUL3 | S585 | ochoa | Cullin-3 (CUL-3) | Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21670212, PubMed:21840486, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:27664236). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205). By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205). The BCR(KBTBD4) E3 ubiquitin ligase complex targets CoREST corepressor complex components RCOR1, KDM1A/LSD1 and HDAC2 for proteasomal degradation with RCOR1 likely to be the primary target while degradation of KDM1A and HDAC2 is likely due to their association with RCOR1 (PubMed:33417871). It also targets RCOR3, MIER2 and MIER3 for proteasomal degradation as well as associated proteins ZNF217 and RREB1 with degradation being dependent on the presence of an ELM2 domain in the target proteins (PubMed:36997086). The BCR(ARMC5) complex mediates premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation by mediating ubiquitination of Pol II subunit POLR2A (PubMed:35687106, PubMed:38225631, PubMed:39504960, PubMed:39667934). Required for 'Lys-63'-linked ubiquitination of large ribosomal subunit protein MRPL12 (PubMed:37526061). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27664236, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:33417871, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:36997086, ECO:0000269|PubMed:37526061, ECO:0000269|PubMed:38225631, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}. |
| Q13620 | CUL4B | S193 | ochoa | Cullin-4B (CUL-4B) | Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14578910, PubMed:16322693, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948, PubMed:30166453, PubMed:33854232, PubMed:33854239). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948). CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460). Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage (PubMed:14578910, PubMed:16678110, PubMed:18593899). Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication (PubMed:16678110). A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948). The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (PubMed:33854232, PubMed:33854239). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:30166453). Required for ubiquitination of cyclin E (CCNE1 or CCNE2), and consequently, normal G1 cell cycle progression (PubMed:16322693, PubMed:19801544). Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism (PubMed:18235224). Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8 (PubMed:18235224). With CUL4A, contributes to ribosome biogenesis (PubMed:26711351). {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:16322693, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:18235224, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19801544, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:30166453, ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854239}. |
| Q13671 | RIN1 | S461 | ochoa | Ras and Rab interactor 1 (Ras inhibitor JC99) (Ras interaction/interference protein 1) | Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. Can affect Ras signaling at different levels. First, by competing with RAF1 protein for binding to activated Ras. Second, by enhancing signaling from ABL1 and ABL2, which regulate cytoskeletal remodeling. Third, by activating RAB5A, possibly by functioning as a guanine nucleotide exchange factor (GEF) for RAB5A, by exchanging bound GDP for free GTP, and facilitating Ras-activated receptor endocytosis. {ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9208849}. |
| Q13733 | ATP1A4 | S377 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-4 (Na(+)/K(+) ATPase alpha-4 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-4) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility. |
| Q13813 | SPTAN1 | S1041 | ochoa | Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin) (Fodrin alpha chain) (Spectrin, non-erythroid alpha subunit) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. |
| Q13813 | SPTAN1 | S1990 | ochoa | Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin) (Fodrin alpha chain) (Spectrin, non-erythroid alpha subunit) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. |
| Q13835 | PKP1 | S142 | ochoa | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q13835 | PKP1 | S174 | psp | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q13838 | DDX39B | S38 | ochoa | Spliceosome RNA helicase DDX39B (EC 3.6.4.13) (56 kDa U2AF65-associated protein) (ATP-dependent RNA helicase p47) (DEAD box protein UAP56) (HLA-B-associated transcript 1 protein) | Involved in nuclear export of spliced and unspliced mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602). The THOC1-THOC2-THOC3 core complex alone is sufficient to promote ATPase activity of DDX39B; in the complex THOC2 is the only component that directly interacts with DDX39B (PubMed:33191911). Associates with SARNP/CIP29, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export (PubMed:37578863). May undergo several rounds of ATP hydrolysis during assembly of TREX to drive subsequent loading of components such as ALYREF/THOC4 and CHTOP onto mRNA. Also associates with pre-mRNA independent of ALYREF/THOC4. Involved in the nuclear export of intronless mRNA; the ATP-bound form is proposed to recruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPase activity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATP hydrolysis is thought to trigger the dissociation from RNA to allow the association of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved in transcription elongation and genome stability. {ECO:0000269|PubMed:11675789, ECO:0000269|PubMed:15585580, ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:17562711, ECO:0000269|PubMed:17984224, ECO:0000269|PubMed:20844015, ECO:0000269|PubMed:22144908, ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:23299939, ECO:0000269|PubMed:33191911, ECO:0000269|PubMed:37578863, ECO:0000269|PubMed:9242493}.; FUNCTION: Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2; the effect of ALYREF/THOC4 is reported conflictingly with [PubMed:23299939] reporting a stimulatory effect. {ECO:0000269|PubMed:23299939, ECO:0000269|PubMed:9242493}.; FUNCTION: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. {ECO:0000269|PubMed:18974867}. |
| Q13905 | RAPGEF1 | S375 | ochoa | Rap guanine nucleotide exchange factor 1 (CRK SH3-binding GNRP) (Guanine nucleotide-releasing factor 2) (Protein C3G) | Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}. |
| Q13950 | RUNX2 | S378 | psp | Runt-related transcription factor 2 (Acute myeloid leukemia 3 protein) (Core-binding factor subunit alpha-1) (CBF-alpha-1) (Oncogene AML-3) (Osteoblast-specific transcription factor 2) (OSF-2) (Polyomavirus enhancer-binding protein 2 alpha A subunit) (PEA2-alpha A) (PEBP2-alpha A) (SL3-3 enhancer factor 1 alpha A subunit) (SL3/AKV core-binding factor alpha A subunit) | Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28703881, PubMed:28738062). Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Inhibits KAT6B-dependent transcriptional activation. {ECO:0000250, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:28505335, ECO:0000269|PubMed:28703881, ECO:0000269|PubMed:28738062}. |
| Q13976 | PRKG1 | S51 | psp | cGMP-dependent protein kinase 1 (cGK 1) (cGK1) (EC 2.7.11.12) (cGMP-dependent protein kinase I) (cGKI) | Serine/threonine protein kinase that acts as a key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates IRAG1 and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling also alters gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle. {ECO:0000269|PubMed:10567269, ECO:0000269|PubMed:11162591, ECO:0000269|PubMed:11723116, ECO:0000269|PubMed:12082086, ECO:0000269|PubMed:14608379, ECO:0000269|PubMed:15194681, ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:8182057}. |
| Q14004 | CDK13 | S1022 | ochoa | Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) | Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}. |
| Q14012 | CAMK1 | S176 | ochoa | Calcium/calmodulin-dependent protein kinase type 1 (EC 2.7.11.17) (CaM kinase I) (CaM-KI) (CaM kinase I alpha) (CaMKI-alpha) | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}. |
| Q14126 | DSG2 | S680 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14126 | DSG2 | S972 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14126 | DSG2 | S999 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14126 | DSG2 | S1068 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14151 | SAFB2 | S283 | ochoa | Scaffold attachment factor B2 (SAF-B2) | Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation. |
| Q14154 | DELE1 | S474 | ochoa | DAP3-binding cell death enhancer 1 (DAP3-binding cell death enhancer 1, long form) (DELE1(L)) (Death ligand signal enhancer) [Cleaved into: DAP3-binding cell death enhancer 1 short form (DELE1(S)) (S-DELE1) (cDELE1)] | Protein kinase activator that acts as a key activator of the integrated stress response (ISR) following various stresses, such as iron deficiency, mitochondrial stress or mitochondrial DNA breaks (PubMed:32132706, PubMed:32132707, PubMed:35388015, PubMed:37327776, PubMed:37550454, PubMed:37832546, PubMed:38340717). Detects impaired protein import and processing in mitochondria, activating the ISR (PubMed:35388015). May also required for the induction of death receptor-mediated apoptosis through the regulation of caspase activation (PubMed:20563667). {ECO:0000269|PubMed:20563667, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:35388015, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:37550454, ECO:0000269|PubMed:37832546, ECO:0000269|PubMed:38340717}.; FUNCTION: [DAP3-binding cell death enhancer 1]: Protein kinase activator that activates the ISR in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting DELE1 localization at the mitochondrial surface, where it binds and activates EIF2AK1/HRI to trigger the ISR. {ECO:0000269|PubMed:37327776}.; FUNCTION: [DAP3-binding cell death enhancer 1 short form]: Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:37832546, PubMed:38340717). It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:37832546). Also acts as an activator of PRKN-independent mitophagy: activates the protein kinase activity of EIF2AK1/HRI in response to mitochondrial damage, promoting eIF-2-alpha (EIF2S1) phosphorylation, leading to mitochondrial localization of EIF2S1 followed by induction of mitophagy (PubMed:38340717). {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:37550454, ECO:0000269|PubMed:37832546, ECO:0000269|PubMed:38340717}. |
| Q14161 | GIT2 | S384 | psp | ARF GTPase-activating protein GIT2 (ARF GAP GIT2) (Cool-interacting tyrosine-phosphorylated protein 2) (CAT-2) (CAT2) (G protein-coupled receptor kinase-interactor 2) (GRK-interacting protein 2) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. {ECO:0000269|PubMed:10896954}. |
| Q14185 | DOCK1 | S1807 | ochoa | Dedicator of cytokinesis protein 1 (180 kDa protein downstream of CRK) (DOCK180) | Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829). Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1 (PubMed:8657152). {ECO:0000269|PubMed:19004829, ECO:0000269|PubMed:8657152}. |
| Q14201 | BTG3 | S146 | ochoa | Protein BTG3 (Abundant in neuroepithelium area protein) (BTG family member 3) (Protein Tob5) | Overexpression impairs serum-induced cell cycle progression from the G0/G1 to S phase. |
| Q14207 | NPAT | S371 | ochoa | Protein NPAT (Nuclear protein of the ataxia telangiectasia mutated locus) (Nuclear protein of the ATM locus) (p220) | Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters. {ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:12665581, ECO:0000269|PubMed:12724424, ECO:0000269|PubMed:14585971, ECO:0000269|PubMed:14612403, ECO:0000269|PubMed:15555599, ECO:0000269|PubMed:15988025, ECO:0000269|PubMed:16131487, ECO:0000269|PubMed:17163457, ECO:0000269|PubMed:17826007, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:17974976, ECO:0000269|PubMed:9472014}. |
| Q14258 | TRIM25 | S340 | ochoa | E3 ubiquitin/ISG15 ligase TRIM25 (EC 6.3.2.n3) (Estrogen-responsive finger protein) (RING finger protein 147) (RING-type E3 ubiquitin transferase) (EC 2.3.2.27) (RING-type E3 ubiquitin transferase TRIM25) (Tripartite motif-containing protein 25) (Ubiquitin/ISG15-conjugating enzyme TRIM25) (Zinc finger protein 147) | Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase (PubMed:16352599). Involved in innate immune defense against viruses by mediating ubiquitination of RIGI and IFIH1 (PubMed:17392790, PubMed:29357390, PubMed:30193849, PubMed:31710640, PubMed:33849980, PubMed:36045682). Mediates 'Lys-63'-linked polyubiquitination of the RIGI N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection (PubMed:17392790, PubMed:23950712). Mediates 'Lys-63'-linked polyubiquitination of IFIH1 (PubMed:30193849). Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway (PubMed:16352599, PubMed:17069755). Mediates estrogen action in various target organs (PubMed:22452784). Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (By similarity). Plays an essential role in the antiviral activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the replication of certain viruses. Mechanistically, mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1 that is required for its optimal binding to target mRNA (PubMed:28060952, PubMed:28202764). Also mediates the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (PubMed:36067236). {ECO:0000250|UniProtKB:Q61510, ECO:0000269|PubMed:16352599, ECO:0000269|PubMed:17069755, ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:22452784, ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:29357390, ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:31710640, ECO:0000269|PubMed:33849980, ECO:0000269|PubMed:36045682, ECO:0000269|PubMed:36067236}. |
| Q14315 | FLNC | S1396 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14517 | FAT1 | S4276 | ochoa | Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form] | [Protocadherin Fat 1]: Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. {ECO:0000250}. |
| Q14517 | FAT1 | S4473 | ochoa | Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form] | [Protocadherin Fat 1]: Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. {ECO:0000250}. |
| Q14524 | SCN5A | S1934 | psp | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q14566 | MCM6 | S268 | ochoa | DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| Q14566 | MCM6 | S798 | ochoa | DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| Q14644 | RASA3 | S282 | ochoa | Ras GTPase-activating protein 3 (GAP1(IP4BP)) (Ins P4-binding protein) | Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4) with high affinity. Might be a specific IP4 receptor. |
| Q14651 | PLS1 | S541 | ochoa | Plastin-1 (Intestine-specific plastin) (I-plastin) | Actin-bundling protein. In the inner ear, it is required for stereocilia formation. Mediates liquid packing of actin filaments that is necessary for stereocilia to grow to their proper dimensions. {ECO:0000250|UniProtKB:Q3V0K9}. |
| Q14674 | ESPL1 | S1305 | psp | Separin (EC 3.4.22.49) (Caspase-like protein ESPL1) (Extra spindle poles-like 1 protein) (Separase) | Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}. |
| Q14676 | MDC1 | S402 | ochoa|psp | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14676 | MDC1 | S1732 | ochoa | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14677 | CLINT1 | S210 | ochoa | Clathrin interactor 1 (Clathrin-interacting protein localized in the trans-Golgi region) (Clint) (Enthoprotin) (Epsin-4) (Epsin-related protein) (EpsinR) | Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly. {ECO:0000269|PubMed:12429846, ECO:0000269|PubMed:12538641}. |
| Q14678 | KANK1 | S195 | ochoa | KN motif and ankyrin repeat domain-containing protein 1 (Ankyrin repeat domain-containing protein 15) (Kidney ankyrin repeat-containing protein) | Adapter protein that links structural and signaling protein complexes positioned to guide microtubule and actin cytoskeleton dynamics during cell morphogenesis (PubMed:22084092, PubMed:24120883). At focal adhesions (FAs) rims, organizes cortical microtubule stabilizing complexes (CMSCs) and directly interacts with major FA component TLN1, forming macromolecular assemblies positioned to control microtubule-actin crosstalk at the cell edge (PubMed:24120883, PubMed:27410476). Recruits KIF21A in CMSCs at axonal growth cones and regulates axon guidance by suppressing microtubule growth without inducing microtubule disassembly once it reaches the cell cortex (PubMed:24120883). Interacts with ARFGEF1 and participates in establishing microtubule-organizing center (MTOC) orientation and directed cell movement in wound healing (PubMed:22084092). Regulates actin stress fiber formation and cell migration by inhibiting RHOA activation in response to growth factors; this function involves phosphorylation through PI3K/Akt signaling and may depend on the competitive interaction with 14-3-3 adapter proteins to sequester them from active complexes (PubMed:18458160, PubMed:25961457). Inhibits the formation of lamellipodia but not of filopodia; this function may depend on the competitive interaction with BAIAP2 to block its association with activated RAC1. Inhibits fibronectin-mediated cell spreading; this function is partially mediated by BAIAP2 (PubMed:19171758). In the nucleus, is involved in beta-catenin-dependent activation of transcription (PubMed:16968744). During cell division, may regulate DAAM1-dependent RHOA activation that signals centrosome maturation and chromosomal segregation. May also be involved in contractile ring formation during cytokinesis (By similarity). Potential tumor suppressor for renal cell carcinoma (Probable). {ECO:0000250|UniProtKB:E9Q238, ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:18458160, ECO:0000269|PubMed:19171758, ECO:0000269|PubMed:22084092, ECO:0000269|PubMed:24120883, ECO:0000269|PubMed:25961457, ECO:0000269|PubMed:27410476, ECO:0000305|PubMed:12133830}. |
| Q14680 | MELK | S171 | psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q14680 | MELK | S343 | psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q14680 | MELK | S431 | ochoa|psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q14684 | RRP1B | S255 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14684 | RRP1B | S338 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14689 | DIP2A | S145 | ochoa | Disco-interacting protein 2 homolog A (DIP2 homolog A) (EC 6.2.1.1) | Catalyzes the de novo synthesis of acetyl-CoA in vitro (By similarity). Promotes acetylation of CTTN, possibly by providing the acetyl donor, ensuring correct dendritic spine morphology and synaptic transmission (By similarity). Binds to follistatin-related protein FSTL1 and may act as a cell surface receptor for FSTL1, contributing to AKT activation and subsequent FSTL1-induced survival and function of endothelial cells and cardiac myocytes (PubMed:20054002). {ECO:0000250|UniProtKB:Q8BWT5, ECO:0000269|PubMed:20054002}. |
| Q14692 | BMS1 | S403 | ochoa | Ribosome biogenesis protein BMS1 homolog (EC 3.6.5.-) (Ribosome assembly protein BMS1 homolog) | GTPase required for the synthesis of 40S ribosomal subunits and for processing of pre-ribosomal RNA (pre-rRNA) at sites A0, A1, and A2. Controls access of pre-rRNA intermediates to RCL1 during ribosome biogenesis by binding RCL1 in a GTP-dependent manner, and delivering it to pre-ribosomes. GTP-binding and/or GTP hydrolysis may induce conformational rearrangements within the BMS1-RCL1 complex allowing the interaction of RCL1 with its RNA substrate. Required for RCL1 import into the nucleus. {ECO:0000250|UniProtKB:Q08965}. |
| Q14721 | KCNB1 | S730 | ochoa | Potassium voltage-gated channel subfamily B member 1 (Delayed rectifier potassium channel 1) (DRK1) (h-DRK1) (Voltage-gated potassium channel subunit Kv2.1) | Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:10484328, PubMed:12560340, PubMed:1283219, PubMed:19074135, PubMed:19717558, PubMed:24901643, PubMed:8081723). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity). {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q03717, ECO:0000269|PubMed:10484328, ECO:0000269|PubMed:11852086, ECO:0000269|PubMed:12060745, ECO:0000269|PubMed:12560340, ECO:0000269|PubMed:1283219, ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:19717558, ECO:0000269|PubMed:23161216, ECO:0000269|PubMed:24901643, ECO:0000269|PubMed:8081723}. |
| Q14761 | PTPRCAP | S99 | ochoa|psp | Protein tyrosine phosphatase receptor type C-associated protein (PTPRC-associated protein) (CD45-associated protein) (CD45-AP) (Lymphocyte phosphatase-associated phosphoprotein) | None |
| Q14761 | PTPRCAP | S172 | ochoa|psp | Protein tyrosine phosphatase receptor type C-associated protein (PTPRC-associated protein) (CD45-associated protein) (CD45-AP) (Lymphocyte phosphatase-associated phosphoprotein) | None |
| Q14764 | MVP | S445 | ochoa | Major vault protein (MVP) (Lung resistance-related protein) | Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases. {ECO:0000269|PubMed:15133037, ECO:0000269|PubMed:16418217, ECO:0000269|PubMed:16441665}. |
| Q14789 | GOLGB1 | S1259 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| Q14789 | GOLGB1 | S1936 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| Q14790 | CASP8 | S347 | psp | Caspase-8 (CASP-8) (EC 3.4.22.61) (Apoptotic cysteine protease) (Apoptotic protease Mch-5) (CAP4) (FADD-homologous ICE/ced-3-like protease) (FADD-like ICE) (FLICE) (ICE-like apoptotic protease 5) (MORT1-associated ced-3 homolog) (MACH) [Cleaved into: Caspase-8 subunit p18; Caspase-8 subunit p10] | Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:16916640, PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:32929201, PubMed:34012073). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376). Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380 (PubMed:18216014, PubMed:27109099). {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:18216014, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:27109099, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32929201, ECO:0000269|PubMed:34012073, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:8681376, ECO:0000269|PubMed:8681377, ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:8962078, ECO:0000269|PubMed:9006941, ECO:0000269|PubMed:9184224}.; FUNCTION: [Isoform 5]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 6]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 7]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade (PubMed:12010809). {ECO:0000269|PubMed:12010809, ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 8]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}. |
| Q14807 | KIF22 | S455 | ochoa | Kinesin-like protein KIF22 (Kinesin-like DNA-binding protein) (Kinesin-like protein 4) | Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA (By similarity). Plays a role in congression of laterally attached chromosomes in NDC80-depleted cells (PubMed:25743205). {ECO:0000250|UniProtKB:Q9I869, ECO:0000269|PubMed:25743205}. |
| Q14966 | ZNF638 | S366 | ochoa | Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) | Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}. |
| Q14966 | ZNF638 | S676 | ochoa | Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) | Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}. |
| Q14980 | NUMA1 | S1105 | ochoa | Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) | Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}. |
| Q14D04 | VEPH1 | S462 | ochoa | Ventricular zone-expressed PH domain-containing protein homolog 1 (Protein melted) | Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}. |
| Q15003 | NCAPH | S201 | ochoa | Condensin complex subunit 2 (Barren homolog protein 1) (Chromosome-associated protein H) (hCAP-H) (Non-SMC condensin I complex subunit H) (XCAP-H homolog) | Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases (PubMed:11136719). Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}. |
| Q15018 | ABRAXAS2 | S354 | ochoa | BRISC complex subunit Abraxas 2 (Abraxas brother protein 1) (Protein FAM175B) | Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148). {ECO:0000250|UniProtKB:Q3TCJ1, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20032457, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25283148}. |
| Q15021 | NCAPD2 | S1310 | ochoa | Condensin complex subunit 1 (Chromosome condensation-related SMC-associated protein 1) (Chromosome-associated protein D2) (hCAP-D2) (Non-SMC condensin I complex subunit D2) (XCAP-D2 homolog) | Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain (PubMed:11136719). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of non-centromeric ultrafine DNA bridges during anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}. |
| Q15027 | ACAP1 | S379 | ochoa | Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1 (Centaurin-beta-1) (Cnt-b1) | GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration. {ECO:0000269|PubMed:11062263, ECO:0000269|PubMed:16256741, ECO:0000269|PubMed:17398097, ECO:0000269|PubMed:17664335, ECO:0000269|PubMed:22645133}. |
| Q15036 | SNX17 | S312 | ochoa | Sorting nexin-17 | Critical regulator of endosomal recycling of numerous surface proteins, including integrins, signaling receptor and channels (PubMed:15121882, PubMed:15769472, PubMed:39587083). Binds to NPxY sequences in the cytoplasmic tails of target cargos (PubMed:21512128). Associates with retriever and CCC complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGB1, ITGB5 and their associated alpha subunits (PubMed:22492727, PubMed:28892079, PubMed:39587083). Also required for maintenance of normal cell surface levels of APP and LRP1 (PubMed:16712798, PubMed:19005208). Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) (PubMed:16712798). {ECO:0000269|PubMed:15121882, ECO:0000269|PubMed:15769472, ECO:0000269|PubMed:16712798, ECO:0000269|PubMed:19005208, ECO:0000269|PubMed:21512128, ECO:0000269|PubMed:22492727, ECO:0000269|PubMed:28892079}. |
| Q15047 | SETDB1 | S1140 | ochoa | Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1) | Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation (PubMed:12869583, PubMed:27237050, PubMed:39096901). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:14536086, PubMed:27732843). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:27732843, ECO:0000269|PubMed:39096901}. |
| Q15052 | ARHGEF6 | S101 | ochoa | Rho guanine nucleotide exchange factor 6 (Alpha-Pix) (COOL-2) (PAK-interacting exchange factor alpha) (Rac/Cdc42 guanine nucleotide exchange factor 6) | Acts as a RAC1 guanine nucleotide exchange factor (GEF). |
| Q15056 | EIF4H | S110 | ochoa | Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) | Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}. |
| Q15058 | KIF14 | S101 | ochoa | Kinesin-like protein KIF14 | Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}. |
| Q15058 | KIF14 | S607 | psp | Kinesin-like protein KIF14 | Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}. |
| Q15149 | PLEC | S224 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15149 | PLEC | S3580 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15155 | NOMO1 | S1202 | ochoa | BOS complex subunit NOMO1 (Nodal modulator 1) (pM5 protein) | Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:32820719, PubMed:36261522). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:36261522). {ECO:0000269|PubMed:32820719, ECO:0000269|PubMed:36261522}. |
| Q15166 | PON3 | S325 | psp | Serum paraoxonase/lactonase 3 (EC 3.1.1.2) (EC 3.1.1.81) (EC 3.1.8.1) | Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents. {ECO:0000269|PubMed:15772423}. |
| Q15185 | PTGES3 | S100 | ochoa | Prostaglandin E synthase 3 (EC 5.3.99.3) (Cytosolic prostaglandin E2 synthase) (cPGES) (Hsp90 co-chaperone) (Progesterone receptor complex p23) (Telomerase-binding protein p23) | Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes (PubMed:11274138, PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway (PubMed:24711448). {ECO:0000269|PubMed:10922363, ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12077419, ECO:0000269|PubMed:24711448}. |
| Q15208 | STK38 | S264 | ochoa | Serine/threonine-protein kinase 38 (EC 2.7.11.1) (NDR1 protein kinase) (Nuclear Dbf2-related kinase 1) | Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441). Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441). Acts as an ufmylation 'reader' in a kinase-independent manner: specifically recognizes and binds mono-ufmylated histone H4 in response to DNA damage, promoting the recruitment of SUV39H1 to the double-strand breaks, resulting in ATM activation (PubMed:32537488). {ECO:0000269|PubMed:12493777, ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:17906693, ECO:0000269|PubMed:32537488, ECO:0000269|PubMed:7761441}. |
| Q15283 | RASA2 | S553 | ochoa | Ras GTPase-activating protein 2 (GTPase-activating protein 1m) (GAP1m) | Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4). |
| Q15286 | RAB35 | S36 | ochoa | Ras-related protein Rab-35 (EC 3.6.5.2) (GTP-binding protein RAY) (Ras-related protein Rab-1C) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:30905672). RAB35 is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane (PubMed:21951725). During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge (PubMed:16950109). May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:Q6PHN9, ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725, ECO:0000269|PubMed:30905672}. |
| Q15291 | RBBP5 | S515 | ochoa | Retinoblastoma-binding protein 5 (RBBP-5) (Retinoblastoma-binding protein RBQ-3) | In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). Does not affect ES cell self-renewal (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (PubMed:19556245). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:19556245). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000250|UniProtKB:Q8BX09, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}. |
| Q15327 | ANKRD1 | S213 | ochoa | Ankyrin repeat domain-containing protein 1 (Cardiac ankyrin repeat protein) (Cytokine-inducible gene C-193 protein) (Cytokine-inducible nuclear protein) | May play an important role in endothelial cell activation. May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes. Induction seems to be correlated with apoptotic cell death in hepatoma cells. {ECO:0000269|PubMed:15805281, ECO:0000269|PubMed:7730328}. |
| Q15345 | LRRC41 | S281 | ochoa | Leucine-rich repeat-containing protein 41 (Protein Muf1) | Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. {ECO:0000269|PubMed:15601820}. |
| Q15365 | PCBP1 | S111 | ochoa | Poly(rC)-binding protein 1 (Alpha-CP1) (Heterogeneous nuclear ribonucleoprotein E1) (hnRNP E1) (Nucleic acid-binding protein SUB2.3) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:15731341, PubMed:7556077, PubMed:7607214, PubMed:8152927). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:P60335, ECO:0000269|PubMed:15731341, ECO:0000269|PubMed:7556077, ECO:0000269|PubMed:7607214, ECO:0000269|PubMed:8152927}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD. {ECO:0000269|PubMed:12414943}. |
| Q15365 | PCBP1 | S332 | ochoa | Poly(rC)-binding protein 1 (Alpha-CP1) (Heterogeneous nuclear ribonucleoprotein E1) (hnRNP E1) (Nucleic acid-binding protein SUB2.3) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:15731341, PubMed:7556077, PubMed:7607214, PubMed:8152927). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:P60335, ECO:0000269|PubMed:15731341, ECO:0000269|PubMed:7556077, ECO:0000269|PubMed:7607214, ECO:0000269|PubMed:8152927}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD. {ECO:0000269|PubMed:12414943}. |
| Q15366 | PCBP2 | S90 | ochoa | Poly(rC)-binding protein 2 (Alpha-CP2) (Heterogeneous nuclear ribonucleoprotein E2) (hnRNP E2) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:12414943, PubMed:7607214). Major cellular poly(rC)-binding protein (PubMed:12414943). Also binds poly(rU) (PubMed:12414943). Acts as a negative regulator of antiviral signaling (PubMed:19881509, PubMed:35322803). Negatively regulates cellular antiviral responses mediated by MAVS signaling (PubMed:19881509). It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation (PubMed:19881509). Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid-like droplets in which CGAS is activated (PubMed:35322803). Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:Q61990, ECO:0000269|PubMed:12414943, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:35322803, ECO:0000269|PubMed:7607214}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12414943, PubMed:24371074). Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943). {ECO:0000269|PubMed:12414943, ECO:0000269|PubMed:24371074}. |
| Q15366 | PCBP2 | S111 | ochoa | Poly(rC)-binding protein 2 (Alpha-CP2) (Heterogeneous nuclear ribonucleoprotein E2) (hnRNP E2) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:12414943, PubMed:7607214). Major cellular poly(rC)-binding protein (PubMed:12414943). Also binds poly(rU) (PubMed:12414943). Acts as a negative regulator of antiviral signaling (PubMed:19881509, PubMed:35322803). Negatively regulates cellular antiviral responses mediated by MAVS signaling (PubMed:19881509). It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation (PubMed:19881509). Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid-like droplets in which CGAS is activated (PubMed:35322803). Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:Q61990, ECO:0000269|PubMed:12414943, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:35322803, ECO:0000269|PubMed:7607214}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12414943, PubMed:24371074). Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943). {ECO:0000269|PubMed:12414943, ECO:0000269|PubMed:24371074}. |
| Q15418 | RPS6KA1 | S72 | ochoa | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q15418 | RPS6KA1 | S307 | ochoa | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q15424 | SAFB | S284 | ochoa | Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) | Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}. |
| Q15428 | SF3A2 | S68 | ochoa | Splicing factor 3A subunit 2 (SF3a66) (Spliceosome-associated protein 62) (SAP 62) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10882114, PubMed:11533230, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:10882114, PubMed:11533230, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3A2 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes, including the Bact complex (PubMed:29360106, PubMed:29361316, PubMed:30315277). Interacts directly with the duplex formed by U2 snRNA and the intron (PubMed:29360106). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:11533230, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:34822310}. |
| Q15569 | TESK1 | S603 | ochoa | Dual specificity testis-specific protein kinase 1 (EC 2.7.12.1) (Testicular protein kinase 1) | Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues (By similarity). Regulates the cellular cytoskeleton by enhancing actin stress fiber formation via phosphorylation of cofilin and by preventing microtubule breakdown via inhibition of TAOK1/MARKK kinase activity (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Positively regulates integrin-mediated cell spreading, via phosphorylation of cofilin (PubMed:15584898). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of ciliary vesicle directional trafficking to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity). {ECO:0000250|UniProtKB:O70146, ECO:0000250|UniProtKB:Q63572, ECO:0000269|PubMed:15584898, ECO:0000269|PubMed:25849865}. |
| Q15596 | NCOA2 | S726 | ochoa | Nuclear receptor coactivator 2 (NCoA-2) (Class E basic helix-loop-helix protein 75) (bHLHe75) (Transcriptional intermediary factor 2) (hTIF2) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:22504882, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:26553876, ECO:0000269|PubMed:8670870, ECO:0000269|PubMed:9430642}. |
| Q15599 | NHERF2 | S269 | ochoa | Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (NHERF-2) (NHE3 kinase A regulatory protein E3KARP) (SRY-interacting protein 1) (SIP-1) (Sodium-hydrogen exchanger regulatory factor 2) (Solute carrier family 9 isoform A3 regulatory factor 2) (Tyrosine kinase activator protein 1) (TKA-1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus. {ECO:0000269|PubMed:10455146, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:9096337}. |
| Q15648 | MED1 | S207 | ochoa | Mediator of RNA polymerase II transcription subunit 1 (Activator-recruited cofactor 205 kDa component) (ARC205) (Mediator complex subunit 1) (Peroxisome proliferator-activated receptor-binding protein) (PBP) (PPAR-binding protein) (Thyroid hormone receptor-associated protein complex 220 kDa component) (Trap220) (Thyroid receptor-interacting protein 2) (TR-interacting protein 2) (TRIP-2) (Vitamin D receptor-interacting protein complex component DRIP205) (p53 regulatory protein RB18A) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (PubMed:10406464, PubMed:11867769, PubMed:12037571, PubMed:12218053, PubMed:12556447, PubMed:14636573, PubMed:15340084, PubMed:15471764, PubMed:15989967, PubMed:16574658, PubMed:9653119). Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). {ECO:0000269|PubMed:10406464, ECO:0000269|PubMed:11867769, ECO:0000269|PubMed:12037571, ECO:0000269|PubMed:12218053, ECO:0000269|PubMed:12556447, ECO:0000269|PubMed:14636573, ECO:0000269|PubMed:15340084, ECO:0000269|PubMed:15471764, ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16574658, ECO:0000269|PubMed:24245781, ECO:0000269|PubMed:9653119}. |
| Q15654 | TRIP6 | S92 | ochoa | Thyroid receptor-interacting protein 6 (TR-interacting protein 6) (TRIP-6) (Opa-interacting protein 1) (OIP-1) (Zyxin-related protein 1) (ZRP-1) | Relays signals from the cell surface to the nucleus to weaken adherens junction and promote actin cytoskeleton reorganization and cell invasiveness. Involved in lysophosphatidic acid-induced cell adhesion and migration. Acts as a transcriptional coactivator for NF-kappa-B and JUN, and mediates the transrepression of these transcription factors induced by glucocorticoid receptor. {ECO:0000269|PubMed:14688263, ECO:0000269|PubMed:15489293, ECO:0000269|PubMed:16624523, ECO:0000269|PubMed:19017743}. |
| Q15699 | ALX1 | S39 | ochoa | ALX homeobox protein 1 (Cartilage homeoprotein 1) (CART-1) | Sequence-specific DNA-binding transcription factor that binds palindromic sequences within promoters and may activate or repress the transcription of a subset of genes (PubMed:8756334, PubMed:9753625). Most probably regulates the expression of genes involved in the development of mesenchyme-derived craniofacial structures. Early on in development, it plays a role in forebrain mesenchyme survival (PubMed:20451171). May also induce epithelial to mesenchymal transition (EMT) through the expression of SNAI1 (PubMed:23288509). {ECO:0000269|PubMed:20451171, ECO:0000269|PubMed:23288509, ECO:0000269|PubMed:8756334, ECO:0000269|PubMed:9753625}. |
| Q15700 | DLG2 | S627 | ochoa | Disks large homolog 2 (Channel-associated protein of synapse-110) (Chapsyn-110) (Postsynaptic density protein PSD-93) | Required for perception of chronic pain through NMDA receptor signaling. Regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord. Interacts with the cytoplasmic tail of NMDA receptor subunits as well as inward rectifying potassium channels. Involved in regulation of synaptic stability at cholinergic synapses. Part of the postsynaptic protein scaffold of excitatory synapses (By similarity). {ECO:0000250}. |
| Q15717 | ELAVL1 | S242 | psp | ELAV-like protein 1 (Hu-antigen R) (HuR) | RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability (PubMed:14517288, PubMed:18285462, PubMed:31358969). Involved in embryonic stem cell (ESC) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESC differentiation (By similarity). Has also been shown to be capable of binding to m6A-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398, PubMed:17632515, PubMed:18285462, PubMed:23519412, PubMed:8626503). Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro (PubMed:8626503). With ZNF385A, binds the 3'-UTR of p53/TP53 mRNA to control their nuclear export induced by CDKN2A. Hence, may regulate p53/TP53 expression and mediate in part the CDKN2A anti-proliferative activity. May also bind with ZNF385A the CCNB1 mRNA (By similarity). Increases the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR (PubMed:29180010). {ECO:0000250|UniProtKB:P70372, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:17632515, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:23519412, ECO:0000269|PubMed:29180010, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:32245947, ECO:0000269|PubMed:8626503}. |
| Q15746 | MYLK | S1151 | ochoa | Myosin light chain kinase, smooth muscle (MLCK) (smMLCK) (EC 2.7.11.18) (Kinase-related protein) (KRP) (Telokin) [Cleaved into: Myosin light chain kinase, smooth muscle, deglutamylated form] | Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, ECO:0000269|PubMed:20453870}. |
| Q15746 | MYLK | S1617 | ochoa | Myosin light chain kinase, smooth muscle (MLCK) (smMLCK) (EC 2.7.11.18) (Kinase-related protein) (KRP) (Telokin) [Cleaved into: Myosin light chain kinase, smooth muscle, deglutamylated form] | Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, ECO:0000269|PubMed:20453870}. |
| Q15785 | TOMM34 | S153 | ochoa | Mitochondrial import receptor subunit TOM34 (hTom34) (Translocase of outer membrane 34 kDa subunit) | Plays a role in the import of cytosolically synthesized preproteins into mitochondria. Binds the mature portion of precursor proteins. Interacts with cellular components, and possesses weak ATPase activity. May be a chaperone-like protein that helps to keep newly synthesized precursors in an unfolded import compatible state. {ECO:0000269|PubMed:10101285, ECO:0000269|PubMed:11913975, ECO:0000269|PubMed:9324309}. |
| Q15796 | SMAD2 | S260 | psp | Mothers against decapentaplegic homolog 2 (MAD homolog 2) (Mothers against DPP homolog 2) (JV18-1) (Mad-related protein 2) (hMAD-2) (SMAD family member 2) (SMAD 2) (Smad2) (hSMAD2) | Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. May act as a tumor suppressor in colorectal carcinoma (PubMed:8752209). {ECO:0000250|UniProtKB:Q62432, ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:9892009}. |
| Q15906 | VPS72 | S107 | ochoa | Vacuolar protein sorting-associated protein 72 homolog (Protein YL-1) (Transcription factor-like 1) | Deposition-and-exchange histone chaperone specific for H2AZ1, specifically chaperones H2AZ1 and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP-dependent exchange of histone H2AZ1/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. {ECO:0000269|PubMed:26974126}. |
| Q16555 | DPYSL2 | S288 | ochoa | Dihydropyrimidinase-related protein 2 (DRP-2) (Collapsin response mediator protein 2) (CRMP-2) (N2A3) (Unc-33-like phosphoprotein 2) (ULIP-2) | Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis. {ECO:0000269|PubMed:11477421, ECO:0000269|PubMed:15466863, ECO:0000269|PubMed:20801876}. |
| Q16647 | PTGIS | S221 | ochoa | Prostacyclin synthase (EC 5.3.99.4) (Hydroperoxy icosatetraenoate dehydratase) (EC 4.2.1.152) (Prostaglandin I2 synthase) | Catalyzes the biosynthesis and metabolism of eicosanoids. Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2), a potent mediator of vasodilation and inhibitor of platelet aggregation (PubMed:12372404, PubMed:15115769, PubMed:18032380, PubMed:25623425). Additionally, displays dehydratase activity, toward hydroperoxyeicosatetraenoates (HPETEs), especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) (PubMed:17459323). {ECO:0000269|PubMed:12372404, ECO:0000269|PubMed:15115769, ECO:0000269|PubMed:17459323, ECO:0000269|PubMed:18032380, ECO:0000269|PubMed:25623425}. |
| Q16665 | HIF1A | S761 | psp | Hypoxia-inducible factor 1-alpha (HIF-1-alpha) (HIF1-alpha) (ARNT-interacting protein) (Basic-helix-loop-helix-PAS protein MOP1) (Class E basic helix-loop-helix protein 78) (bHLHe78) (Member of PAS protein 1) (PAS domain-containing protein 8) | Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:16543236, PubMed:9887100). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}. |
| Q16678 | CYP1B1 | S112 | ochoa | Cytochrome P450 1B1 (EC 1.14.14.1) (CYPIB1) (Hydroperoxy icosatetraenoate dehydratase) (EC 4.2.1.152) | A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity). {ECO:0000250|UniProtKB:Q64429, ECO:0000269|PubMed:10426814, ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:15258110, ECO:0000269|PubMed:20972997, ECO:0000269|PubMed:21068195}. |
| Q16706 | MAN2A1 | S943 | ochoa | Alpha-mannosidase 2 (EC 3.2.1.114) (Golgi alpha-mannosidase II) (AMan II) (Man II) (Mannosidase alpha class 2A member 1) (Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase) | Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway. {ECO:0000250|UniProtKB:P28494}. |
| Q16760 | DGKD | S731 | ochoa | Diacylglycerol kinase delta (DAG kinase delta) (EC 2.7.1.107) (130 kDa diacylglycerol kinase) (Diglyceride kinase delta) (DGK-delta) | Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:12200442, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable). By controlling the levels of diacylglycerol, regulates for instance the PKC and EGF receptor signaling pathways and plays a crucial role during development (By similarity). May also regulate clathrin-dependent endocytosis (PubMed:17880279). {ECO:0000250|UniProtKB:E9PUQ8, ECO:0000269|PubMed:12200442, ECO:0000269|PubMed:17880279, ECO:0000269|PubMed:23949095, ECO:0000305}. |
| Q16778 | H2BC21 | S57 | ochoa | Histone H2B type 2-E (H2B-clustered histone 21) (Histone H2B-GL105) (Histone H2B.q) (H2B/q) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.; FUNCTION: Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid. |
| Q16825 | PTPN21 | S863 | ochoa | Tyrosine-protein phosphatase non-receptor type 21 (EC 3.1.3.48) (Protein-tyrosine phosphatase D1) | None |
| Q17RC7 | EXOC3L4 | S52 | ochoa | Exocyst complex component 3-like protein 4 | None |
| Q29RF7 | PDS5A | S178 | ochoa | Sister chromatid cohesion protein PDS5 homolog A (Cell proliferation-inducing gene 54 protein) (Sister chromatid cohesion protein 112) (SCC-112) | Probable regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15855230, ECO:0000269|PubMed:19907496}. |
| Q29RF7 | PDS5A | S1159 | ochoa | Sister chromatid cohesion protein PDS5 homolog A (Cell proliferation-inducing gene 54 protein) (Sister chromatid cohesion protein 112) (SCC-112) | Probable regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15855230, ECO:0000269|PubMed:19907496}. |
| Q2LD37 | BLTP1 | S1364 | ochoa | Bridge-like lipid transfer protein family member 1 (Fragile site-associated protein) | Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum (Probable). Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics (PubMed:30906834). Acts as a regulator of phagocytosis (PubMed:31540829). {ECO:0000269|PubMed:30906834, ECO:0000269|PubMed:31540829, ECO:0000305|PubMed:35015055, ECO:0000305|PubMed:35491307}. |
| Q2LD37 | BLTP1 | S2300 | ochoa | Bridge-like lipid transfer protein family member 1 (Fragile site-associated protein) | Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum (Probable). Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics (PubMed:30906834). Acts as a regulator of phagocytosis (PubMed:31540829). {ECO:0000269|PubMed:30906834, ECO:0000269|PubMed:31540829, ECO:0000305|PubMed:35015055, ECO:0000305|PubMed:35491307}. |
| Q2M1Z3 | ARHGAP31 | S954 | ochoa | Rho GTPase-activating protein 31 (Cdc42 GTPase-activating protein) | Functions as a GTPase-activating protein (GAP) for RAC1 and CDC42. Required for cell spreading, polarized lamellipodia formation and cell migration. {ECO:0000269|PubMed:12192056, ECO:0000269|PubMed:16519628}. |
| Q2NKX8 | ERCC6L | S807 | ochoa | DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) | DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}. |
| Q2PPJ7 | RALGAPA2 | S360 | ochoa | Ral GTPase-activating protein subunit alpha-2 (250 kDa substrate of Akt) (AS250) (p220) | Catalytic subunit of the heterodimeric RalGAP2 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q2QGD7 | ZXDC | S631 | ochoa | Zinc finger protein ZXDC (ZXD-like zinc finger protein) | Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes. {ECO:0000269|PubMed:16600381, ECO:0000269|PubMed:17493635, ECO:0000269|PubMed:17696781}. |
| Q2TAK8 | PWWP3A | S540 | ochoa | PWWP domain-containing DNA repair factor 3A (PWWP3A) (Mutated melanoma-associated antigen 1) (MUM-1) (PWWP domain-containing protein MUM1) (Protein expandere) | Involved in the DNA damage response pathway by contributing to the maintenance of chromatin architecture. Recruited to the vicinity of DNA breaks by TP53BP1 and plays an accessory role to facilitate damage-induced chromatin changes and promoting chromatin relaxation. Required for efficient DNA repair and cell survival following DNA damage. {ECO:0000269|PubMed:20347427}. |
| Q2TAZ0 | ATG2A | S1402 | ochoa | Autophagy-related protein 2 homolog A | Lipid transfer protein involved in autophagosome assembly (PubMed:28561066, PubMed:30952800, PubMed:31271352). Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion (PubMed:30952800, PubMed:31271352). Binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, and extracts phospholipids from the membrane source and transfers them to ATG9 (ATG9A or ATG9B) to the IM for membrane expansion (PubMed:30952800, PubMed:31271352). Lipid transfer activity is enhanced by WIPI1 and WDR45/WIPI4, which promote ATG2A-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31271352). Also regulates lipid droplets morphology and distribution within the cell (PubMed:22219374, PubMed:28561066). {ECO:0000269|PubMed:22219374, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:30952800, ECO:0000269|PubMed:31271352}. |
| Q3V6T2 | CCDC88A | S1675 | ochoa|psp | Girdin (Akt phosphorylation enhancer) (APE) (Coiled-coil domain-containing protein 88A) (G alpha-interacting vesicle-associated protein) (GIV) (Girders of actin filament) (Hook-related protein 1) (HkRP1) | Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:16139227, PubMed:19211784, PubMed:20462955, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}. |
| Q3YBM2 | TMEM176B | S245 | ochoa | Transmembrane protein 176B (Protein LR8) | May play a role in the process of maturation of dendritic cells. Required for the development of cerebellar granule cells (By similarity). {ECO:0000250}. |
| Q3YBR2 | TBRG1 | S18 | ochoa | Transforming growth factor beta regulator 1 (Nuclear interactor of ARF and Mdm2) | Acts as a growth inhibitor. Can activate p53/TP53, causes G1 arrest and collaborates with CDKN2A to restrict proliferation, but does not require either protein to inhibit DNA synthesis. Redistributes CDKN2A into the nucleoplasm. Involved in maintaining chromosomal stability. {ECO:0000269|PubMed:17110379}. |
| Q49A88 | CCDC14 | S126 | ochoa | Coiled-coil domain-containing protein 14 | Negatively regulates centriole duplication. Negatively regulates CEP63 and CDK2 centrosomal localization. {ECO:0000269|PubMed:24613305, ECO:0000269|PubMed:26297806}. |
| Q4KMG0 | CDON | S1076 | ochoa | Cell adhesion molecule-related/down-regulated by oncogenes | Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells (By similarity). {ECO:0000250}. |
| Q4KMP7 | TBC1D10B | S248 | ochoa | TBC1 domain family member 10B (Rab27A-GAP-beta) | Acts as a GTPase-activating protein for RAB3A, RAB22A, RAB27A, and RAB35. Does not act on RAB2A and RAB6A. {ECO:0000269|PubMed:16923811, ECO:0000269|PubMed:19077034}. |
| Q4KMP7 | TBC1D10B | S318 | ochoa | TBC1 domain family member 10B (Rab27A-GAP-beta) | Acts as a GTPase-activating protein for RAB3A, RAB22A, RAB27A, and RAB35. Does not act on RAB2A and RAB6A. {ECO:0000269|PubMed:16923811, ECO:0000269|PubMed:19077034}. |
| Q4L180 | FILIP1L | S992 | ochoa | Filamin A-interacting protein 1-like (130 kDa GPBP-interacting protein) (90 kDa GPBP-interacting protein) (Protein down-regulated in ovarian cancer 1) (DOC-1) | Acts as a regulator of the antiangiogenic activity on endothelial cells. When overexpressed in endothelial cells, leads to inhibition of cell proliferation and migration and an increase in apoptosis. Inhibits melanoma growth When expressed in tumor-associated vasculature. {ECO:0000269|PubMed:18794120}. |
| Q53EL6 | PDCD4 | S317 | ochoa | Programmed cell death protein 4 (Neoplastic transformation inhibitor protein) (Nuclear antigen H731-like) (Protein 197/15a) | Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA (By similarity). {ECO:0000250, ECO:0000269|PubMed:16357133, ECO:0000269|PubMed:16449643, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:18296639, ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291}. |
| Q53ET0 | CRTC2 | S70 | ochoa | CREB-regulated transcription coactivator 2 (Transducer of regulated cAMP response element-binding protein 2) (TORC-2) (Transducer of CREB protein 2) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:14536081, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:16809310, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223}. |
| Q53ET0 | CRTC2 | S79 | ochoa | CREB-regulated transcription coactivator 2 (Transducer of regulated cAMP response element-binding protein 2) (TORC-2) (Transducer of CREB protein 2) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:14536081, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:16809310, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223}. |
| Q53GL0 | PLEKHO1 | S221 | ochoa | Pleckstrin homology domain-containing family O member 1 (PH domain-containing family O member 1) (C-Jun-binding protein) (JBP) (Casein kinase 2-interacting protein 1) (CK2-interacting protein 1) (CKIP-1) (Osteoclast maturation-associated gene 120 protein) | Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP). May function to target CK2 to the plasma membrane thereby serving as an adapter to facilitate the phosphorylation of CP by protein kinase 2 (CK2). Appears to target ATM to the plasma membrane. Appears to also inhibit tumor cell growth by inhibiting AKT-mediated cell-survival. Also implicated in PI3K-regulated muscle differentiation, the regulation of AP-1 activity (plasma membrane bound AP-1 regulator that translocates to the nucleus) and the promotion of apoptosis induced by tumor necrosis factor TNF. When bound to PKB, it inhibits it probably by decreasing PKB level of phosphorylation. {ECO:0000269|PubMed:14729969, ECO:0000269|PubMed:15706351, ECO:0000269|PubMed:15831458, ECO:0000269|PubMed:16325375, ECO:0000269|PubMed:16987810, ECO:0000269|PubMed:17197158, ECO:0000269|PubMed:17942896}. |
| Q53GS7 | GLE1 | S41 | ochoa | mRNA export factor GLE1 (hGLE1) (GLE1 RNA export mediator) (GLE1-like protein) (Nucleoporin GLE1) | Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm. May be involved in the terminal step of the mRNA transport through the nuclear pore complex (NPC). {ECO:0000269|PubMed:12668658, ECO:0000269|PubMed:16000379, ECO:0000269|PubMed:9618489}. |
| Q53H12 | AGK | S350 | ochoa | Acylglycerol kinase, mitochondrial (hAGK) (EC 2.7.1.107) (EC 2.7.1.138) (EC 2.7.1.94) (Multiple substrate lipid kinase) (HsMuLK) (MuLK) (Multi-substrate lipid kinase) | Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (PubMed:15939762). Does not phosphorylate sphingosine (PubMed:15939762). Phosphorylates ceramide (By similarity). Phosphorylates 1,2-dioleoylglycerol more rapidly than 2,3-dioleoylglycerol (By similarity). Independently of its lipid kinase activity, acts as a component of the TIM22 complex (PubMed:28712724, PubMed:28712726). The TIM22 complex mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane by forming a twin-pore translocase that uses the membrane potential as the external driving force (PubMed:28712724, PubMed:28712726). In the TIM22 complex, required for the import of a subset of metabolite carriers into mitochondria, such as ANT1/SLC25A4 and SLC25A24, while it is not required for the import of TIMM23 (PubMed:28712724). Overexpression increases the formation and secretion of LPA, resulting in transactivation of EGFR and activation of the downstream MAPK signaling pathway, leading to increased cell growth (PubMed:15939762). {ECO:0000250|UniProtKB:Q9ESW4, ECO:0000269|PubMed:15939762, ECO:0000269|PubMed:28712724, ECO:0000269|PubMed:28712726}. |
| Q53LP3 | SOWAHC | S408 | ochoa | Ankyrin repeat domain-containing protein SOWAHC (Ankyrin repeat domain-containing protein 57) (Protein sosondowah homolog C) | None |
| Q53S48 | STON1-GTF2A1L | S244 | ochoa | Stonin-1 (Stoned B-like factor) | May be involved in the endocytic machinery. {ECO:0000256|ARBA:ARBA00059680}. |
| Q53S58 | TMEM177 | S275 | ochoa | Transmembrane protein 177 | Plays a role in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation and is required for the stabilization of COX20 and the newly synthesized MT-CO2/COX2 protein. {ECO:0000269|PubMed:29154948}. |
| Q562E7 | WDR81 | S670 | ochoa | WD repeat-containing protein 81 | Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (PubMed:28404643). May also be involved in maintenance of normal mitochondrial structure and organization (By similarity). {ECO:0000250|UniProtKB:Q5ND34, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989, ECO:0000269|PubMed:28404643}. |
| Q58FF3 | HSP90B2P | S60 | ochoa | Putative endoplasmin-like protein (Putative heat shock protein 90 kDa beta member 2) | Putative molecular chaperone. {ECO:0000250}. |
| Q5BJD5 | TMEM41B | S35 | ochoa | Transmembrane protein 41B (Protein stasimon) | Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes (PubMed:33850023, PubMed:33929485, PubMed:34015269). Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine (PubMed:33850023, PubMed:33929485, PubMed:34015269). Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by ATG2 (ATG2A or ATG2B) to mediate autophagosome assembly (PubMed:30093494, PubMed:30126924, PubMed:30933966, PubMed:33850023, PubMed:33929485, PubMed:34015269, PubMed:34043740). In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required (PubMed:33850023). Required for normal motor neuron development (By similarity). {ECO:0000250|UniProtKB:A1A5V7, ECO:0000269|PubMed:30093494, ECO:0000269|PubMed:30126924, ECO:0000269|PubMed:30933966, ECO:0000269|PubMed:33850023, ECO:0000269|PubMed:33929485, ECO:0000269|PubMed:34015269, ECO:0000269|PubMed:34043740}.; FUNCTION: (Microbial infection) Critical host factor required for infection by human coronaviruses SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E, as well as all flaviviruses tested such as Zika virus and Yellow fever virus (PubMed:33338421, PubMed:33382968). Required post-entry of the virus to facilitate the ER membrane remodeling necessary to form replication organelles (PubMed:33382968). {ECO:0000269|PubMed:33338421, ECO:0000269|PubMed:33382968, ECO:0000269|PubMed:34043740}. |
| Q5BKX6 | SLC45A4 | S389 | ochoa | Solute carrier family 45 member 4 | Proton-associated sucrose transporter. May be able to transport also glucose and fructose. {ECO:0000250|UniProtKB:Q0P5V9}. |
| Q5BKZ1 | ZNF326 | S130 | ochoa | DBIRD complex subunit ZNF326 (Zinc finger protein 326) (Zinc finger protein interacting with mRNPs and DBC1) | Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. May play a role in neuronal differentiation and is able to bind DNA and activate expression in vitro. {ECO:0000269|PubMed:22446626}. |
| Q5CZC0 | FSIP2 | S3175 | ochoa | Fibrous sheath-interacting protein 2 | Plays a role in spermatogenesis. {ECO:0000305|PubMed:30137358}. |
| Q5CZC0 | FSIP2 | S3858 | ochoa | Fibrous sheath-interacting protein 2 | Plays a role in spermatogenesis. {ECO:0000305|PubMed:30137358}. |
| Q5FWE3 | PRRT3 | S865 | ochoa | Proline-rich transmembrane protein 3 | None |
| Q5JPB2 | ZNF831 | S439 | ochoa | Zinc finger protein 831 | None |
| Q5JRX3 | PITRM1 | S261 | ochoa | Presequence protease, mitochondrial (hPreP) (EC 3.4.24.-) (Pitrilysin metalloproteinase 1) (Metalloprotease 1) (hMP1) | Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing (PubMed:10360838, PubMed:16849325, PubMed:19196155, PubMed:24931469). Has an ATP-independent activity (PubMed:16849325). Specifically cleaves peptides in the range of 5 to 65 residues (PubMed:19196155). Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference (PubMed:10360838, PubMed:19196155, PubMed:24931469). Degrades the transit peptides of mitochondrial proteins after their cleavage (PubMed:19196155). Also degrades other unstructured peptides (PubMed:19196155). It is also able to degrade amyloid-beta protein 40, one of the peptides produced by APP processing, when it accumulates in mitochondrion (PubMed:16849325, PubMed:24931469, PubMed:26697887). It is a highly efficient protease, at least toward amyloid-beta protein 40 (PubMed:24931469, PubMed:29383861, PubMed:29764912). Cleaves that peptide at a specific position and is probably not processive, releasing digested peptides intermediates that can be further cleaved subsequently (PubMed:24931469). It is also able to degrade amyloid-beta protein 42 (PubMed:29764912). {ECO:0000269|PubMed:10360838, ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:24931469, ECO:0000269|PubMed:26697887, ECO:0000269|PubMed:29383861, ECO:0000269|PubMed:29764912}. |
| Q5JSZ5 | PRRC2B | S1395 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JSZ5 | PRRC2B | S1486 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JSZ5 | PRRC2B | S1808 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JWF2 | GNAS | S697 | ochoa | Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas (EC 3.6.5.-) (Adenylate cyclase-stimulating G alpha protein) (Extra large alphas protein) (XLalphas) | Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as Gnas isoforms. {ECO:0000250|UniProtKB:Q6R0H7}. |
| Q5M775 | SPECC1 | S617 | ochoa | Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) | None |
| Q5M775 | SPECC1 | S840 | ochoa | Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) | None |
| Q5M7Z0 | RNFT1 | S72 | ochoa | E3 ubiquitin-protein ligase RNFT1 (EC 2.3.2.27) (Protein PTD016) (RING finger and transmembrane domain-containing protein 1) | E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis. {ECO:0000269|PubMed:27485036}. |
| Q5PRF9 | SAMD4B | S299 | ochoa | Protein Smaug homolog 2 (Smaug 2) (hSmaug2) (Sterile alpha motif domain-containing protein 4B) (SAM domain-containing protein 4B) | Has transcriptional repressor activity. Overexpression inhibits the transcriptional activities of AP-1, p53/TP53 and CDKN1A. {ECO:0000269|PubMed:20510020}. |
| Q5QJE6 | DNTTIP2 | S481 | ochoa | Deoxynucleotidyltransferase terminal-interacting protein 2 (Estrogen receptor-binding protein) (LPTS-interacting protein 2) (LPTS-RP2) (Terminal deoxynucleotidyltransferase-interacting factor 2) (TdIF2) (TdT-interacting factor 2) | Regulates the transcriptional activity of DNTT and ESR1. May function as a chromatin remodeling protein (PubMed:12786946, PubMed:15047147). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:12786946, ECO:0000269|PubMed:15047147, ECO:0000269|PubMed:34516797}. |
| Q5QNW6 | H2BC18 | S57 | ochoa | Histone H2B type 2-F (H2B-clustered histone 18) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q5R3F8 | ELFN2 | S636 | ochoa | Protein phosphatase 1 regulatory subunit 29 (Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2) (Leucine-rich repeat and fibronectin type-III domain-containing protein 6) (Leucine-rich repeat-containing protein 62) | Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000269|PubMed:19389623}. |
| Q5SNT2 | TMEM201 | S473 | ochoa | Transmembrane protein 201 (Spindle-associated membrane protein 1) | Critical regulator of angiogenesis and endothelial cell (EC) migration (PubMed:35311970). Promotes the migration of endothelial cells, which is essential for angiogenesis (PubMed:35311970). Interacts with the linker of nucleoskeleton and cytoskeleton (LINC) complex, which plays a vital role in connecting the cell's cytoskeleton to the nuclear envelope (PubMed:35311970). This interaction is essential for maintaining cellular structure and facilitating the movement of endothelial cells, which is critical for proper vascular development (PubMed:35311970). Involved in nuclear movement during fibroblast polarization and migration (By similarity). Overexpression can recruit Ran GTPase to the nuclear periphery (PubMed:27541860). {ECO:0000250|UniProtKB:A2A8U2, ECO:0000269|PubMed:35311970, ECO:0000305|PubMed:27541860}.; FUNCTION: [Isoform 2]: May define a distinct membrane domain in the vicinity of the mitotic spindle (PubMed:19494128). Involved in the organization of the nuclear envelope implicating EMD, SUN1 and A-type lamina (PubMed:21610090). {ECO:0000269|PubMed:19494128, ECO:0000269|PubMed:21610090}. |
| Q5SSJ5 | HP1BP3 | S176 | ochoa | Heterochromatin protein 1-binding protein 3 (Protein HP1-BP74) | Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity (PubMed:24830416). Mediates chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance and self-renewal (PubMed:25100860). {ECO:0000269|PubMed:24830416, ECO:0000269|PubMed:25100860}. |
| Q5T0W9 | FAM83B | S514 | ochoa | Protein FAM83B | Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. {ECO:0000269|PubMed:22886302, ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:23912460}. |
| Q5T0Z8 | C6orf132 | S260 | ochoa | Uncharacterized protein C6orf132 | None |
| Q5T1R4 | HIVEP3 | S720 | ochoa | Transcription factor HIVEP3 (Human immunodeficiency virus type I enhancer-binding protein 3) (Kappa-B and V(D)J recombination signal sequences-binding protein) (Kappa-binding protein 1) (KBP-1) (Zinc finger protein ZAS3) | Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-alpha-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and pro-inflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation. {ECO:0000269|PubMed:11161801}. |
| Q5T200 | ZC3H13 | S1423 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5T3I0 | GPATCH4 | S137 | ochoa | G patch domain-containing protein 4 | None |
| Q5T4S7 | UBR4 | S2892 | ochoa | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| Q5T5P2 | KIAA1217 | S468 | ochoa | Sickle tail protein homolog | Required for normal development of intervertebral disks. {ECO:0000250|UniProtKB:A2AQ25}. |
| Q5T5X7 | BEND3 | S181 | ochoa | BEN domain-containing protein 3 | Transcriptional repressor which associates with the NoRC (nucleolar remodeling complex) complex and plays a key role in repressing rDNA transcription. The sumoylated form modulates the stability of the NoRC complex component BAZ2A/TIP5 by controlling its USP21-mediated deubiquitination (PubMed:21914818, PubMed:26100909). Binds to unmethylated major satellite DNA and is involved in the recruitment of the Polycomb repressive complex 2 (PRC2) to major satellites (By similarity). Stimulates the ERCC6L translocase and ATPase activities (PubMed:28977671). {ECO:0000250|UniProtKB:Q6PAL0, ECO:0000269|PubMed:21914818, ECO:0000269|PubMed:26100909, ECO:0000269|PubMed:28977671}. |
| Q5T5X7 | BEND3 | S489 | ochoa | BEN domain-containing protein 3 | Transcriptional repressor which associates with the NoRC (nucleolar remodeling complex) complex and plays a key role in repressing rDNA transcription. The sumoylated form modulates the stability of the NoRC complex component BAZ2A/TIP5 by controlling its USP21-mediated deubiquitination (PubMed:21914818, PubMed:26100909). Binds to unmethylated major satellite DNA and is involved in the recruitment of the Polycomb repressive complex 2 (PRC2) to major satellites (By similarity). Stimulates the ERCC6L translocase and ATPase activities (PubMed:28977671). {ECO:0000250|UniProtKB:Q6PAL0, ECO:0000269|PubMed:21914818, ECO:0000269|PubMed:26100909, ECO:0000269|PubMed:28977671}. |
| Q5T5Y3 | CAMSAP1 | S1060 | ochoa | Calmodulin-regulated spectrin-associated protein 1 | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}. |
| Q5T5Y3 | CAMSAP1 | S1252 | ochoa | Calmodulin-regulated spectrin-associated protein 1 | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}. |
| Q5T6F0 | DCAF12 | S20 | ochoa | DDB1- and CUL4-associated factor 12 (Centrosome-related protein TCC52) (Testis cancer centrosome-related protein) (WD repeat-containing protein 40A) | Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:16949367, PubMed:16964240, PubMed:29779948). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948). The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:31267705). Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12) complex is required for starvation-induced autophagy (PubMed:31267705). Also directly recognizes the C-terminal glutamate-leucine (Glu-Leu) degron as an alternative degron in proteins such as MOV10, leading to their ubiquitination and degradation. Controls the protein level of MOV10 during spermatogenesis and in T cells, especially after their activation (PubMed:34065512). {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:31267705, ECO:0000269|PubMed:34065512}. |
| Q5T6F2 | UBAP2 | S956 | ochoa | Ubiquitin-associated protein 2 (UBAP-2) (RNA polymerase II degradation factor UBAP2) | Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). May promote the degradation of ANXA2 (PubMed:27121050). {ECO:0000269|PubMed:27121050, ECO:0000269|PubMed:35633597}. |
| Q5T7B8 | KIF24 | S603 | ochoa | Kinesin-like protein KIF24 | Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles. Mediates depolymerization of microtubules of centriolar origin, possibly to suppress aberrant cilia formation (PubMed:21620453). Following activation by NEK2 involved in disassembly of primary cilium during G2/M phase but does not disassemble fully formed ciliary axonemes. As cilium assembly and disassembly is proposed to coexist in a dynamic equilibrium may suppress nascent cilium assembly and, potentially, ciliar re-assembly in cells that have already disassembled their cilia ensuring the completion of cilium removal in the later stages of the cell cycle (PubMed:26290419). Plays an important role in recruiting MPHOSPH9, a negative regulator of cilia formation to the distal end of mother centriole (PubMed:30375385). {ECO:0000269|PubMed:21620453, ECO:0000269|PubMed:26290419, ECO:0000269|PubMed:30375385}. |
| Q5TBA9 | FRY | S723 | ochoa | Protein furry homolog | Plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity by promoting PLK1 activity at the spindle poles in early mitosis. May function as a scaffold promoting the interaction between AURKA and PLK1, thereby enhancing AURKA-mediated PLK1 phosphorylation. {ECO:0000269|PubMed:22753416}. |
| Q5TCX8 | MAP3K21 | S635 | ochoa | Mitogen-activated protein kinase kinase kinase 21 (EC 2.7.11.25) (Mitogen-activated protein kinase kinase kinase MLK4) (Mixed lineage kinase 4) | Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1 pathways. {ECO:0000269|PubMed:21602844}. |
| Q5TH69 | ARFGEF3 | S1049 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (ARFGEF family member 3) | Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8, ECO:0000269|PubMed:19496786}. |
| Q5THJ4 | VPS13D | S1034 | ochoa | Intermembrane lipid transfer protein VPS13D (Vacuolar protein sorting-associated protein 13D) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Functions in promoting mitochondrial clearance by mitochondrial autophagy (mitophagy), also possibly by positively regulating mitochondrial fission (PubMed:29307555, PubMed:29604224). Mitophagy plays an important role in regulating cell health and mitochondrial size and homeostasis. {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:29307555, ECO:0000269|PubMed:29604224}. |
| Q5U5Q3 | MEX3C | S152 | ochoa | RNA-binding E3 ubiquitin-protein ligase MEX3C (EC 2.3.2.27) (RING finger and KH domain-containing protein 2) (RING finger protein 194) (RING-type E3 ubiquitin transferase MEX3C) | E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNA decay. RNA binding is sufficient to prevent translation, but ubiquitin ligase activity is required for mRNA degradation. {ECO:0000269|PubMed:22863774, ECO:0000269|PubMed:23446422}. |
| Q5VST9 | OBSCN | S125 | ochoa | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q5VT25 | CDC42BPA | S222 | psp | Serine/threonine-protein kinase MRCK alpha (EC 2.7.11.1) (CDC42-binding protein kinase alpha) (DMPK-like alpha) (Myotonic dystrophy kinase-related CDC42-binding kinase alpha) (MRCK alpha) (Myotonic dystrophy protein kinase-like alpha) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration (PubMed:15723050, PubMed:9092543, PubMed:9418861). Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates: PPP1R12A, LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in TFRC-mediated iron uptake (PubMed:20188707). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). Triggers the formation of an extrusion apical actin ring required for epithelial extrusion of apoptotic cells (PubMed:29162624). {ECO:0000250|UniProtKB:Q3UU96, ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11399775, ECO:0000269|PubMed:15723050, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:20188707, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:29162624, ECO:0000269|PubMed:9092543, ECO:0000269|PubMed:9418861}. |
| Q5VT25 | CDC42BPA | S1003 | psp | Serine/threonine-protein kinase MRCK alpha (EC 2.7.11.1) (CDC42-binding protein kinase alpha) (DMPK-like alpha) (Myotonic dystrophy kinase-related CDC42-binding kinase alpha) (MRCK alpha) (Myotonic dystrophy protein kinase-like alpha) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration (PubMed:15723050, PubMed:9092543, PubMed:9418861). Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates: PPP1R12A, LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in TFRC-mediated iron uptake (PubMed:20188707). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). Triggers the formation of an extrusion apical actin ring required for epithelial extrusion of apoptotic cells (PubMed:29162624). {ECO:0000250|UniProtKB:Q3UU96, ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11399775, ECO:0000269|PubMed:15723050, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:20188707, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:29162624, ECO:0000269|PubMed:9092543, ECO:0000269|PubMed:9418861}. |
| Q5VT52 | RPRD2 | S381 | ochoa | Regulation of nuclear pre-mRNA domain-containing protein 2 | None |
| Q5VUB5 | FAM171A1 | S443 | ochoa | Protein FAM171A1 (Astroprincin) (APCN) | Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation. {ECO:0000269|PubMed:30312582}. |
| Q5VUJ6 | LRCH2 | S351 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 2 | May play a role in the organization of the cytoskeleton. {ECO:0000250|UniProtKB:Q960C5, ECO:0000250|UniProtKB:Q96II8}. |
| Q5VWG9 | TAF3 | S114 | ochoa | Transcription initiation factor TFIID subunit 3 (140 kDa TATA box-binding protein-associated factor) (TBP-associated factor 3) (Transcription initiation factor TFIID 140 kDa subunit) (TAF(II)140) (TAF140) (TAFII-140) (TAFII140) | The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (PubMed:33795473). TAF3 forms the TFIID-A module together with TAF5 and TBP (PubMed:33795473). Required in complex with TBPL2 for the differentiation of myoblasts into myocytes (PubMed:11438666). The TAF3-TBPL2 complex replaces TFIID at specific promoters at an early stage in the differentiation process (PubMed:11438666). {ECO:0000269|PubMed:11438666, ECO:0000269|PubMed:33795473}. |
| Q5VYS8 | TUT7 | S706 | ochoa | Terminal uridylyltransferase 7 (TUTase 7) (EC 2.7.7.52) (Zinc finger CCHC domain-containing protein 6) | Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also functions as an integral regulator of microRNA biogenesiS using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828, PubMed:28671666). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (PubMed:25979828). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:18172165, PubMed:19703396, PubMed:22898984, PubMed:25480299, PubMed:25979828, PubMed:28671666). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (PubMed:30122351). {ECO:0000250|UniProtKB:Q5BLK4, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:22898984, ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:25979828, ECO:0000269|PubMed:28671666, ECO:0000269|PubMed:30122351}. |
| Q5VZ89 | DENND4C | S263 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5VZ89 | DENND4C | S538 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5VZ89 | DENND4C | S909 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5VZK9 | CARMIL1 | S1165 | ochoa | F-actin-uncapping protein LRRC16A (CARMIL homolog) (Capping protein regulator and myosin 1 linker protein 1) (Capping protein, Arp2/3 and myosin-I linker homolog 1) (Capping protein, Arp2/3 and myosin-I linker protein 1) (Leucine-rich repeat-containing protein 16A) | Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:19846667). {ECO:0000269|PubMed:16054028, ECO:0000269|PubMed:19846667}. |
| Q5VZL5 | ZMYM4 | S306 | ochoa | Zinc finger MYM-type protein 4 (Zinc finger protein 262) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q5W0B1 | OBI1 | S416 | ochoa | ORC ubiquitin ligase 1 (OBI1) (EC 2.3.2.27) (RING finger protein 219) | E3 ubiquitin ligase essential for DNA replication origin activation during S phase (PubMed:31160578). Acts as a replication origin selector which selects the origins to be fired and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase (PubMed:31160578). {ECO:0000269|PubMed:31160578}. |
| Q63HR2 | TNS2 | S102 | ochoa | Tensin-2 (EC 3.1.3.48) (C1 domain-containing phosphatase and tensin homolog) (C1-TEN) (Tensin-like C1 domain-containing phosphatase) | Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin (PubMed:15817639, PubMed:23401856). Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain (PubMed:30092354). In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy (PubMed:23401856, PubMed:30092354). Negatively regulates PI3K-AKT pathway activation (PubMed:15817639, PubMed:23401856, PubMed:30092354). Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex (PubMed:28955049). Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria (PubMed:28955049). Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix (PubMed:20069572). {ECO:0000250|UniProtKB:Q8CGB6, ECO:0000269|PubMed:15817639, ECO:0000269|PubMed:20069572, ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:28955049, ECO:0000269|PubMed:30092354}. |
| Q66K74 | MAP1S | S321 | ochoa | Microtubule-associated protein 1S (MAP-1S) (BPY2-interacting protein 1) (Microtubule-associated protein 8) (Variable charge Y chromosome 2-interacting protein 1) (VCY2-interacting protein 1) (VCY2IP-1) [Cleaved into: MAP1S heavy chain; MAP1S light chain] | Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles (By similarity). {ECO:0000250, ECO:0000269|PubMed:15899810, ECO:0000269|PubMed:17234756}. |
| Q684P5 | RAP1GAP2 | S574 | ochoa | Rap1 GTPase-activating protein 2 (Rap1GAP2) (GTPase-activating Rap/Ran-GAP domain-like protein 4) | GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. {ECO:0000269|PubMed:15632203}. |
| Q68CZ2 | TNS3 | S439 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q68D51 | DENND2C | S504 | ochoa | DENN domain-containing protein 2C | Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}. |
| Q68DK7 | MSL1 | S213 | ochoa | Male-specific lethal 1 homolog (MSL-1) (Male-specific lethal 1-like 1) (MSL1-like 1) (Male-specific lethal-1 homolog 1) | Non-catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at 'Lys-16' (H4K16ac), an epigenetic mark that prevents chromatin compaction (PubMed:16227571, PubMed:16543150, PubMed:33837287). The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac (PubMed:33837287). The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome (By similarity). X up-regulation is required to compensate for autosomal biallelic expression (By similarity). The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA (By similarity). Within the MSL complex, acts as a scaffold to tether MSL3 and KAT8 together for enzymatic activity regulation (PubMed:22547026). Greatly enhances MSL2 E3 ubiquitin ligase activity, promoting monoubiquitination of histone H2B at 'Lys-34' (H2BK34Ub) (PubMed:21726816, PubMed:30930284). This modification in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (PubMed:21726816). {ECO:0000250|UniProtKB:Q6PDM1, ECO:0000269|PubMed:16227571, ECO:0000269|PubMed:16543150, ECO:0000269|PubMed:21726816, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:30930284, ECO:0000269|PubMed:33837287}. |
| Q68DN1 | SPATA31H1 | S178 | ochoa | Spermatogenesis-associated protein 31H1 | None |
| Q68DQ2 | CRYBG3 | S387 | ochoa | Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) | [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}. |
| Q68EM7 | ARHGAP17 | S610 | ochoa | Rho GTPase-activating protein 17 (Rho-type GTPase-activating protein 17) (RhoGAP interacting with CIP4 homologs protein 1) (RICH-1) | Rho GTPase-activating protein involved in the maintenance of tight junction by regulating the activity of CDC42, thereby playing a central role in apical polarity of epithelial cells. Specifically acts as a GTPase activator for the CDC42 GTPase by converting it to an inactive GDP-bound state. The complex formed with AMOT acts by regulating the uptake of polarity proteins at tight junctions, possibly by deciding whether tight junction transmembrane proteins are recycled back to the plasma membrane or sent elsewhere. Participates in the Ca(2+)-dependent regulation of exocytosis, possibly by catalyzing GTPase activity of Rho family proteins and by inducing the reorganization of the cortical actin filaments. Acts as a GTPase activator in vitro for RAC1. {ECO:0000269|PubMed:11431473, ECO:0000269|PubMed:16678097}. |
| Q6DT37 | CDC42BPG | S1524 | ochoa | Serine/threonine-protein kinase MRCK gamma (EC 2.7.11.1) (CDC42-binding protein kinase gamma) (DMPK-like gamma) (Myotonic dystrophy kinase-related CDC42-binding kinase gamma) (MRCK gamma) (MRCKG) (Myotonic dystrophy protein kinase-like gamma) (Myotonic dystrophy protein kinase-like alpha) | May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation (By similarity). {ECO:0000250|UniProtKB:Q5VT25, ECO:0000269|PubMed:15194684}. |
| Q6EKJ0 | GTF2IRD2B | S500 | ochoa | General transcription factor II-I repeat domain-containing protein 2B (GTF2I repeat domain-containing protein 2B) (Transcription factor GTF2IRD2-beta) | None |
| Q6GQQ9 | OTUD7B | S63 | ochoa | OTU domain-containing protein 7B (EC 3.4.19.12) (Cellular zinc finger anti-NF-kappa-B protein) (Cezanne) (Zinc finger A20 domain-containing protein 1) (Zinc finger protein Cezanne) | Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses (PubMed:18178551). In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (By similarity). Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:11463333, PubMed:20622874, PubMed:23827681, PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin (PubMed:12682062). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked deubiquitination of MLST8, thereby promoting assembly of the mTORC2 complex, while inibiting formation of the mTORC1 complex (PubMed:28489822). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584, ECO:0000269|PubMed:28489822}. |
| Q6GYQ0 | RALGAPA1 | S503 | ochoa | Ral GTPase-activating protein subunit alpha-1 (GAP-related-interacting partner to E12) (GRIPE) (GTPase-activating Rap/Ran-GAP domain-like 1) (Tuberin-like protein 1) (p240) | Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q6GYQ0 | RALGAPA1 | S691 | ochoa | Ral GTPase-activating protein subunit alpha-1 (GAP-related-interacting partner to E12) (GRIPE) (GTPase-activating Rap/Ran-GAP domain-like 1) (Tuberin-like protein 1) (p240) | Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q6GYQ0 | RALGAPA1 | S832 | ochoa | Ral GTPase-activating protein subunit alpha-1 (GAP-related-interacting partner to E12) (GRIPE) (GTPase-activating Rap/Ran-GAP domain-like 1) (Tuberin-like protein 1) (p240) | Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q6ICG6 | KIAA0930 | S358 | ochoa | Uncharacterized protein KIAA0930 | None |
| Q6ICG6 | KIAA0930 | S362 | ochoa | Uncharacterized protein KIAA0930 | None |
| Q6IQ32 | ADNP2 | S869 | ochoa | Activity-dependent neuroprotector homeobox protein 2 (ADNP homeobox protein 2) (Zinc finger protein 508) | May be involved in transcriptional regulation. May play a role in neuronal function; perhaps involved in protection of brain tissues from oxidative stress. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CHC8}. |
| Q6KC79 | NIPBL | S1243 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6KC79 | NIPBL | S2684 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6MZZ7 | CAPN13 | S501 | ochoa | Calpain-13 (EC 3.4.22.-) (Calcium-activated neutral proteinase 13) (CANP 13) | Probable non-lysosomal thiol-protease. {ECO:0000250}. |
| Q6N021 | TET2 | S69 | ochoa | Methylcytosine dioxygenase TET2 (EC 1.14.11.80) | Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. {ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493, ECO:0000269|PubMed:21817016, ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:32518946}. |
| Q6N021 | TET2 | S936 | ochoa | Methylcytosine dioxygenase TET2 (EC 1.14.11.80) | Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. {ECO:0000269|PubMed:19483684, ECO:0000269|PubMed:21057493, ECO:0000269|PubMed:21817016, ECO:0000269|PubMed:23222540, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24315485, ECO:0000269|PubMed:32518946}. |
| Q6N022 | TENM4 | S2585 | ochoa | Teneurin-4 (Ten-4) (Protein Odd Oz/ten-m homolog 4) (Tenascin-M4) (Ten-m4) (Teneurin transmembrane protein 4) | Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Plays a role in the establishment of the anterior-posterior axis during gastrulation. Regulates the differentiation and cellular process formation of oligodendrocytes and myelination of small-diameter axons in the central nervous system (CNS) (PubMed:26188006). Promotes activation of focal adhesion kinase. May function as a cellular signal transducer (By similarity). {ECO:0000250|UniProtKB:Q3UHK6, ECO:0000269|PubMed:26188006}. |
| Q6NUJ5 | PWWP2B | S291 | ochoa | PWWP domain-containing protein 2B | Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes (PubMed:30228260). Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z (PubMed:30228260). Plays a role in facilitating transcriptional elongation through regulation of histone acetylation (By similarity). Negatively regulates brown adipocyte thermogenesis by interacting with and stabilizing HDAC1 at the UCP1 gene promoter, thereby promoting histone deacetylation at the promoter leading to the repression of UCP1 expression (By similarity). {ECO:0000250|UniProtKB:Q69Z61, ECO:0000269|PubMed:30228260}. |
| Q6NUP7 | PPP4R4 | S150 | ochoa | Serine/threonine-protein phosphatase 4 regulatory subunit 4 | Putative regulatory subunit of serine/threonine-protein phosphatase 4. |
| Q6NUQ4 | TMEM214 | S456 | ochoa | Transmembrane protein 214 | Critical mediator, in cooperation with CASP4, of endoplasmic reticulum-stress induced apoptosis. Required or the activation of CASP4 following endoplasmic reticulum stress. {ECO:0000269|PubMed:23661706}. |
| Q6NXE6 | ARMC6 | S80 | ochoa | Armadillo repeat-containing protein 6 | None |
| Q6NY19 | KANK3 | S293 | ochoa | KN motif and ankyrin repeat domain-containing protein 3 (Ankyrin repeat domain-containing protein 47) | May be involved in the control of cytoskeleton formation by regulating actin polymerization. |
| Q6P0N0 | MIS18BP1 | S299 | ochoa | Mis18-binding protein 1 (Kinetochore-associated protein KNL-2 homolog) (HsKNL-2) (P243) | Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038, ECO:0000269|PubMed:17339379}. |
| Q6P0N0 | MIS18BP1 | S335 | ochoa | Mis18-binding protein 1 (Kinetochore-associated protein KNL-2 homolog) (HsKNL-2) (P243) | Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038, ECO:0000269|PubMed:17339379}. |
| Q6P1J9 | CDC73 | S212 | ochoa | Parafibromin (Cell division cycle protein 73 homolog) (Hyperparathyroidism 2 protein) | Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors. {ECO:0000269|PubMed:15580289, ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15923622, ECO:0000269|PubMed:16630820, ECO:0000269|PubMed:16989776, ECO:0000269|PubMed:19136632, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}. |
| Q6P2E9 | EDC4 | S565 | ochoa | Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) | In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}. |
| Q6P2E9 | EDC4 | S1154 | ochoa | Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) | In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}. |
| Q6P2E9 | EDC4 | S1380 | ochoa | Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) | In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}. |
| Q6P4E1 | GOLM2 | S328 | ochoa | Protein GOLM2 (Cancer susceptibility candidate gene 4 protein) (CASC4) (Golgi membrane protein 2) | None |
| Q6P4E1 | GOLM2 | S332 | ochoa | Protein GOLM2 (Cancer susceptibility candidate gene 4 protein) (CASC4) (Golgi membrane protein 2) | None |
| Q6P995 | FAM171B | S716 | ochoa | Protein FAM171B | None |
| Q6P9A1 | ZNF530 | S131 | ochoa | Zinc finger protein 530 | May be involved in transcriptional regulation. {ECO:0000250}. |
| Q6PCE3 | PGM2L1 | S175 | ochoa | Glucose 1,6-bisphosphate synthase (EC 2.7.1.106) (PMMLP) (Phosphoglucomutase-2-like 1) | Glucose 1,6-bisphosphate synthase using 1,3-bisphosphoglycerate as a phosphate donor and a series of 1-phosphate sugars, including glucose 1-phosphate, mannose 1-phosphate, ribose 1-phosphate and deoxyribose 1-phosphate, as acceptors (PubMed:17804405). In vitro, also exhibits very low phosphopentomutase and phosphoglucomutase activity which are most probably not physiologically relevant (PubMed:17804405). {ECO:0000269|PubMed:17804405, ECO:0000269|PubMed:18927083, ECO:0000269|PubMed:33979636}. |
| Q6PFW1 | PPIP5K1 | S1037 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 1) (Histidine acid phosphatase domain-containing protein 2A) (IP6 kinase) (Inositol pyrophosphate synthase 1) (InsP6 and PP-IP5 kinase 1) (VIP1 homolog) (hsVIP1) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress. {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752}. |
| Q6PJF5 | RHBDF2 | S102 | ochoa | Inactive rhomboid protein 2 (iRhom2) (Rhomboid 5 homolog 2) (Rhomboid family member 2) (Rhomboid veinlet-like protein 5) (Rhomboid veinlet-like protein 6) | Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. {ECO:0000250|UniProtKB:Q80WQ6}. |
| Q6PJG2 | MIDEAS | S996 | ochoa | Mitotic deacetylase-associated SANT domain protein (ELM2 and SANT domain-containing protein 1) | None |
| Q6PJT7 | ZC3H14 | S240 | ochoa | Zinc finger CCCH domain-containing protein 14 (Mammalian suppressor of tau pathology-2) (MSUT-2) (Renal carcinoma antigen NY-REN-37) | RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs (PubMed:39461343). Acts by binding to both exon-intron boundary and 3'-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome (PubMed:39461343). Required for spermatogenesis via involvement in circRNA biogenesis (PubMed:39461343). Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation (PubMed:27563065). Also binds the poly(A) tail of mRNAs; controlling poly(A) length in neuronal cells (PubMed:17630287, PubMed:24671764). {ECO:0000269|PubMed:17630287, ECO:0000269|PubMed:24671764, ECO:0000269|PubMed:27563065, ECO:0000269|PubMed:39461343}. |
| Q6PJT7 | ZC3H14 | S365 | ochoa | Zinc finger CCCH domain-containing protein 14 (Mammalian suppressor of tau pathology-2) (MSUT-2) (Renal carcinoma antigen NY-REN-37) | RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs (PubMed:39461343). Acts by binding to both exon-intron boundary and 3'-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome (PubMed:39461343). Required for spermatogenesis via involvement in circRNA biogenesis (PubMed:39461343). Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation (PubMed:27563065). Also binds the poly(A) tail of mRNAs; controlling poly(A) length in neuronal cells (PubMed:17630287, PubMed:24671764). {ECO:0000269|PubMed:17630287, ECO:0000269|PubMed:24671764, ECO:0000269|PubMed:27563065, ECO:0000269|PubMed:39461343}. |
| Q6PJT7 | ZC3H14 | S579 | ochoa | Zinc finger CCCH domain-containing protein 14 (Mammalian suppressor of tau pathology-2) (MSUT-2) (Renal carcinoma antigen NY-REN-37) | RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs (PubMed:39461343). Acts by binding to both exon-intron boundary and 3'-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome (PubMed:39461343). Required for spermatogenesis via involvement in circRNA biogenesis (PubMed:39461343). Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation (PubMed:27563065). Also binds the poly(A) tail of mRNAs; controlling poly(A) length in neuronal cells (PubMed:17630287, PubMed:24671764). {ECO:0000269|PubMed:17630287, ECO:0000269|PubMed:24671764, ECO:0000269|PubMed:27563065, ECO:0000269|PubMed:39461343}. |
| Q6SPF0 | SAMD1 | S399 | ochoa | Sterile alpha motif domain-containing protein 1 (SAM domain-containing protein 1) (Atherin) | Unmethylated CpG islands (CGIs)-binding protein which localizes to H3K4me3-decorated CGIs, where it acts as a transcriptional repressor (PubMed:33980486). Tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs (PubMed:33980486). Plays a role in atherogenesis by binding with LDL on cell surface and promoting LDL oxidation which leads to the formation of foam cell (PubMed:16159594, PubMed:34006929). {ECO:0000269|PubMed:16159594, ECO:0000269|PubMed:33980486, ECO:0000269|PubMed:34006929}. |
| Q6UB99 | ANKRD11 | S437 | ochoa | Ankyrin repeat domain-containing protein 11 (Ankyrin repeat-containing cofactor 1) | Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (By similarity). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (PubMed:15184363). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). May also regulate bone homeostasis (By similarity). {ECO:0000250|UniProtKB:E9Q4F7, ECO:0000269|PubMed:15184363, ECO:0000269|PubMed:25556659}. |
| Q6UUV7 | CRTC3 | S62 | ochoa|psp | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UUV7 | CRTC3 | S273 | ochoa | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UUV9 | CRTC1 | S64 | ochoa | CREB-regulated transcription coactivator 1 (Mucoepidermoid carcinoma translocated protein 1) (Transducer of regulated cAMP response element-binding protein 1) (TORC-1) (Transducer of CREB protein 1) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons (By similarity). In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock. {ECO:0000250|UniProtKB:Q157S1, ECO:0000250|UniProtKB:Q68ED7, ECO:0000269|PubMed:23699513}.; FUNCTION: (Microbial infection) Plays a role of coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:16809310}. |
| Q6UWE0 | LRSAM1 | S231 | ochoa | E3 ubiquitin-protein ligase LRSAM1 (EC 2.3.2.27) (Leucine-rich repeat and sterile alpha motif-containing protein 1) (RING-type E3 ubiquitin transferase LRSAM1) (Tsg101-associated ligase) (hTAL) | E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098). {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322, ECO:0000269|PubMed:25484098}. |
| Q6UX73 | C16orf89 | S174 | ochoa | UPF0764 protein C16orf89 | None |
| Q6UXY8 | TMC5 | S149 | ochoa | Transmembrane channel-like protein 5 | Probable component of an ion channel (Probable). Molecular function hasn't been characterized yet (Probable). {ECO:0000305}. |
| Q6UXY8 | TMC5 | S184 | ochoa | Transmembrane channel-like protein 5 | Probable component of an ion channel (Probable). Molecular function hasn't been characterized yet (Probable). {ECO:0000305}. |
| Q6WCQ1 | MPRIP | S891 | ochoa | Myosin phosphatase Rho-interacting protein (M-RIP) (Rho-interacting protein 3) (RIP3) (p116Rip) | Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells. {ECO:0000250|UniProtKB:P97434, ECO:0000269|PubMed:15545284, ECO:0000269|PubMed:16257966}. |
| Q6WKZ4 | RAB11FIP1 | S365 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6XZF7 | DNMBP | S316 | ochoa | Dynamin-binding protein (Scaffold protein Tuba) | Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells (PubMed:17015620, PubMed:19767742). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (PubMed:20479467). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (By similarity). {ECO:0000250|UniProtKB:E2RP94, ECO:0000250|UniProtKB:Q6TXD4, ECO:0000269|PubMed:17015620, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20479467}. |
| Q6XZF7 | DNMBP | S482 | ochoa | Dynamin-binding protein (Scaffold protein Tuba) | Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells (PubMed:17015620, PubMed:19767742). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (PubMed:20479467). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (By similarity). {ECO:0000250|UniProtKB:E2RP94, ECO:0000250|UniProtKB:Q6TXD4, ECO:0000269|PubMed:17015620, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20479467}. |
| Q6XZF7 | DNMBP | S996 | ochoa | Dynamin-binding protein (Scaffold protein Tuba) | Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells (PubMed:17015620, PubMed:19767742). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (PubMed:20479467). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (By similarity). {ECO:0000250|UniProtKB:E2RP94, ECO:0000250|UniProtKB:Q6TXD4, ECO:0000269|PubMed:17015620, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20479467}. |
| Q6ZMR3 | LDHAL6A | S161 | ochoa | L-lactate dehydrogenase A-like 6A (LDHA-like protein 6A) (EC 1.1.1.27) | Catalyzes the interconversion of L-lactate and pyruvate with nicotinamide adenine dinucleotide NAD(+) as a coenzyme (PubMed:18351441). Significantly increases the transcriptional activity of JUN, when overexpressed. {ECO:0000269|PubMed:18351441}. |
| Q6ZN17 | LIN28B | S105 | ochoa | Protein lin-28 homolog B (Lin-28B) | Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA (PubMed:22118463). Does not act on pri-miR21 (PubMed:22118463). The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation (PubMed:19703396). This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent (PubMed:22118463). Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression (By similarity). When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth. {ECO:0000250|UniProtKB:Q45KJ6, ECO:0000269|PubMed:16971064, ECO:0000269|PubMed:18951094, ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:22118463}. |
| Q6ZNJ1 | NBEAL2 | S770 | ochoa | Neurobeachin-like protein 2 | Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}. |
| Q6ZNL6 | FGD5 | S594 | ochoa | FYVE, RhoGEF and PH domain-containing protein 5 (Zinc finger FYVE domain-containing protein 23) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Mediates VEGF-induced CDC42 activation. May regulate proangiogenic action of VEGF in vascular endothelial cells, including network formation, directional movement and proliferation. May play a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:22328776}. |
| Q6ZSZ5 | ARHGEF18 | S71 | ochoa | Rho guanine nucleotide exchange factor 18 (114 kDa Rho-specific guanine nucleotide exchange factor) (p114-Rho-GEF) (p114RhoGEF) (Septin-associated RhoGEF) (SA-RhoGEF) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. Also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950). {ECO:0000269|PubMed:11085924, ECO:0000269|PubMed:14512443, ECO:0000269|PubMed:15558029, ECO:0000269|PubMed:22006950, ECO:0000269|PubMed:28132693}. |
| Q6ZSZ6 | TSHZ1 | S919 | ochoa | Teashirt homolog 1 (Antigen NY-CO-33) (Serologically defined colon cancer antigen 33) | Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential). {ECO:0000305}. |
| Q6ZT07 | TBC1D9 | S415 | ochoa | TBC1 domain family member 9 (TBC1 domain family member 9A) | May act as a GTPase-activating protein for Rab family protein(s). |
| Q6ZTU2 | EP400P1 | S185 | ochoa | Putative EP400-like protein (EP400 pseudogene 1) | None |
| Q6ZU65 | UBN2 | S584 | ochoa | Ubinuclein-2 | None |
| Q6ZU80 | CEP128 | S1033 | ochoa | Centrosomal protein of 128 kDa (Cep128) | None |
| Q6ZUJ8 | PIK3AP1 | S696 | ochoa | Phosphoinositide 3-kinase adapter protein 1 (B-cell adapter for phosphoinositide 3-kinase) (B-cell phosphoinositide 3-kinase adapter protein 1) | Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. {ECO:0000269|PubMed:15893754}. |
| Q6ZUJ8 | PIK3AP1 | S720 | ochoa | Phosphoinositide 3-kinase adapter protein 1 (B-cell adapter for phosphoinositide 3-kinase) (B-cell phosphoinositide 3-kinase adapter protein 1) | Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. {ECO:0000269|PubMed:15893754}. |
| Q6ZVF9 | GPRIN3 | S526 | ochoa | G protein-regulated inducer of neurite outgrowth 3 (GRIN3) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q6ZVL6 | KIAA1549L | S1274 | ochoa | UPF0606 protein KIAA1549L | None |
| Q6ZVM7 | TOM1L2 | S424 | ochoa | TOM1-like protein 2 (Target of Myb-like protein 2) | Acts as a MYO6/Myosin VI adapter protein that targets myosin VI to endocytic structures (PubMed:23023224). May also play a role in recruiting clathrin to endosomes (PubMed:16412388). May regulate growth factor-induced mitogenic signaling (PubMed:16479011). {ECO:0000269|PubMed:16412388, ECO:0000269|PubMed:16479011, ECO:0000269|PubMed:23023224}. |
| Q702N8 | XIRP1 | S205 | ochoa | Xin actin-binding repeat-containing protein 1 (Cardiomyopathy-associated protein 1) | Protects actin filaments from depolymerization (PubMed:15454575). Required for correct cardiac intercalated disk ultrastructure via maintenance of cell-cell adhesion stability, and as a result maintains cardiac organ morphology, conductance and heart beat rhythm (By similarity). Required for development of normal skeletal muscle morphology and muscle fiber type composition (By similarity). Plays a role in regulating muscle satellite cell activation and survival, as a result promotes muscle fiber recovery from injury and fatigue (By similarity). {ECO:0000250|UniProtKB:O70373, ECO:0000269|PubMed:15454575}. |
| Q709C8 | VPS13C | S839 | ochoa | Intermembrane lipid transfer protein VPS13C (Vacuolar protein sorting-associated protein 13C) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential (PubMed:26942284). Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization (PubMed:26942284). {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:26942284}. |
| Q71U36 | TUBA1A | S379 | ochoa | Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 3) (Tubulin B-alpha-1) (Tubulin alpha-3 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q76L83 | ASXL2 | S1319 | ochoa | Putative Polycomb group protein ASXL2 (Additional sex combs-like protein 2) | Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility (By similarity). Involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as peroxisome proliferator-activated receptor gamma (PPARG). Acts as coactivator for PPARG and enhances its adipocyte differentiation-inducing activity; the function seems to involve differential recruitment of acetylated and methylated histone H3. Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:30664650, PubMed:36180891). The PR-DUB complex is an epigenetic regulator of gene expression and acts as a transcriptional coactivator, affecting genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:30664650, PubMed:36180891). ASXL1, ASXL2 and ASXL3 function redundantly in the PR-DUB complex (By similarity) (PubMed:30664650). The ASXL proteins are essential for chromatin recruitment and transcriptional activation of associated genes (By similarity). ASXL1 and ASXL2 are important for BAP1 protein stability (PubMed:30664650). {ECO:0000250, ECO:0000250|UniProtKB:Q8BZ32, ECO:0000269|PubMed:21047783, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:36180891}. |
| Q7L2E3 | DHX30 | S260 | ochoa | ATP-dependent RNA helicase DHX30 (EC 3.6.4.13) (DEAH box protein 30) | RNA-dependent helicase (PubMed:29100085). Plays an important role in the assembly of the mitochondrial large ribosomal subunit (PubMed:25683715, PubMed:29100085). Required for optimal function of the zinc-finger antiviral protein ZC3HAV1 (By similarity). Associates with mitochondrial DNA (PubMed:18063578). Involved in nervous system development and differentiation through its involvement in the up-regulation of a number of genes which are required for neurogenesis, including GSC, NCAM1, neurogenin, and NEUROD (By similarity). {ECO:0000250|UniProtKB:Q5BJS0, ECO:0000250|UniProtKB:Q99PU8, ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:25683715, ECO:0000269|PubMed:29100085}. |
| Q7L2Z9 | CENPQ | S249 | ochoa|psp | Centromere protein Q (CENP-Q) | Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex (PubMed:16622420). Plays an important role in chromosome congression and in the recruitment of CENP-O complex (which comprises CENPO, CENPP, CENPQ and CENPU), CENPE and PLK1 to the kinetochores (PubMed:25395579). {ECO:0000269|PubMed:16622420, ECO:0000269|PubMed:25395579}. |
| Q7L590 | MCM10 | S548 | ochoa | Protein MCM10 homolog (HsMCM10) | Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. Additionally, plays a role in preventing DNA damage during replication. Key effector of the RBBP6 and ZBTB38-mediated regulation of DNA-replication and common fragile sites stability; acts as a direct target of transcriptional repression by ZBTB38 (PubMed:24726359). {ECO:0000269|PubMed:11095689, ECO:0000269|PubMed:15136575, ECO:0000269|PubMed:17699597, ECO:0000269|PubMed:19608746, ECO:0000269|PubMed:24726359, ECO:0000269|PubMed:32865517}. |
| Q7L5Y9 | MAEA | S308 | ochoa | E3 ubiquitin-protein transferase MAEA (EC 2.3.2.27) (Cell proliferation-inducing gene 5 protein) (Erythroblast macrophage protein) (Human lung cancer oncogene 10 protein) (HLC-10) (Macrophage erythroblast attacher) (P44EMLP) | Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex (PubMed:29911972). MAEA is required for normal cell proliferation (PubMed:29911972). The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (PubMed:29911972). Plays a role in erythroblast enucleation during erythrocyte maturation and in the development of mature macrophages (By similarity). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (PubMed:9763581). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis. Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (By similarity). May contribute to nuclear architecture and cells division events (Probable). {ECO:0000250|UniProtKB:Q4VC33, ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:9763581, ECO:0000305|PubMed:16510120}. |
| Q7L8C5 | SYT13 | S58 | ochoa | Synaptotagmin-13 (Synaptotagmin XIII) (SytXIII) | May be involved in transport vesicle docking to the plasma membrane. {ECO:0000250}. |
| Q7LBC6 | KDM3B | S1284 | ochoa | Lysine-specific demethylase 3B (EC 1.14.11.65) (JmjC domain-containing histone demethylation protein 2B) (Jumonji domain-containing protein 1B) (Nuclear protein 5qNCA) ([histone H3]-dimethyl-L-lysine(9) demethylase 3B) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity. {ECO:0000269|PubMed:16603237}. |
| Q7RTP6 | MICAL3 | S1433 | ochoa | [F-actin]-monooxygenase MICAL3 (EC 1.14.13.225) (Molecule interacting with CasL protein 3) (MICAL-3) | Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission. {ECO:0000269|PubMed:21596566, ECO:0000269|PubMed:24440334}. |
| Q7Z2K8 | GPRIN1 | S734 | ochoa | G protein-regulated inducer of neurite outgrowth 1 (GRIN1) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q7Z2W4 | ZC3HAV1 | S101 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z2W4 | ZC3HAV1 | S302 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z2W4 | ZC3HAV1 | S346 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z2W4 | ZC3HAV1 | S417 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z2Y5 | NRK | S1031 | ochoa | Nik-related protein kinase (EC 2.7.11.1) | May phosphorylate cofilin-1 and induce actin polymerization through this process, during the late stages of embryogenesis. Involved in the TNF-alpha-induced signaling pathway (By similarity). {ECO:0000250}. |
| Q7Z3C6 | ATG9A | S642 | ochoa | Autophagy-related protein 9A (APG9-like 1) (mATG9) | Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:22456507, PubMed:27510922, PubMed:29437695, PubMed:32513819, PubMed:32610138, PubMed:33106659, PubMed:33468622, PubMed:33850023). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome (PubMed:16940348, PubMed:22456507, PubMed:33106659). Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion (PubMed:33106659). Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1 (PubMed:30917996). In addition to autophagy, also plays a role in necrotic cell death (By similarity). {ECO:0000250|UniProtKB:Q68FE2, ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:27510922, ECO:0000269|PubMed:29437695, ECO:0000269|PubMed:30917996, ECO:0000269|PubMed:32513819, ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659, ECO:0000269|PubMed:33468622, ECO:0000269|PubMed:33850023}. |
| Q7Z3G6 | PRICKLE2 | S740 | ochoa | Prickle-like protein 2 | None |
| Q7Z3J3 | RGPD4 | S381 | ochoa | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q7Z3K6 | MIER3 | S114 | ochoa | Mesoderm induction early response protein 3 (Mi-er3) | Transcriptional repressor. {ECO:0000250}. |
| Q7Z406 | MYH14 | S42 | ochoa | Myosin-14 (Myosin heavy chain 14) (Myosin heavy chain, non-muscle IIc) (Non-muscle myosin heavy chain IIc) (NMHC II-C) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. {ECO:0000250}. |
| Q7Z434 | MAVS | S416 | ochoa | Mitochondrial antiviral-signaling protein (MAVS) (CARD adapter inducing interferon beta) (Cardif) (Interferon beta promoter stimulator protein 1) (IPS-1) (Putative NF-kappa-B-activating protein 031N) (Virus-induced-signaling adapter) (VISA) | Adapter required for innate immune defense against viruses (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:21170385, PubMed:23087404, PubMed:27992402, PubMed:33139700, PubMed:37582970). Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFNB and RANTES (CCL5) (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:20628368, PubMed:21170385, PubMed:23087404, PubMed:25636800, PubMed:27736772, PubMed:33110251). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (PubMed:20451243). Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response (PubMed:20451243). May activate the same pathways following detection of extracellular dsRNA by TLR3 (PubMed:16153868). May protect cells from apoptosis (PubMed:16125763). Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria (PubMed:23582325). {ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20451243, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27736772, ECO:0000269|PubMed:27992402, ECO:0000269|PubMed:33110251, ECO:0000269|PubMed:33139700, ECO:0000269|PubMed:37582970}. |
| Q7Z460 | CLASP1 | S704 | ochoa | CLIP-associating protein 1 (Cytoplasmic linker-associated protein 1) (Multiple asters homolog 1) (Protein Orbit homolog 1) (hOrbit1) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}. |
| Q7Z460 | CLASP1 | S787 | ochoa | CLIP-associating protein 1 (Cytoplasmic linker-associated protein 1) (Multiple asters homolog 1) (Protein Orbit homolog 1) (hOrbit1) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}. |
| Q7Z4W1 | DCXR | S38 | ochoa | L-xylulose reductase (XR) (EC 1.1.1.10) (Carbonyl reductase II) (Dicarbonyl/L-xylulose reductase) (Kidney dicarbonyl reductase) (kiDCR) (Short chain dehydrogenase/reductase family 20C member 1) (Sperm surface protein P34H) | Catalyzes the NADPH-dependent reduction of several pentoses, tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose. Participates in the uronate cycle of glucose metabolism. May play a role in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thereby preventing osmolytic stress from occurring in the renal tubules. |
| Q7Z591 | AKNA | S1102 | ochoa | Microtubule organization protein AKNA (AT-hook-containing transcription factor) | Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (By similarity). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (By similarity). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (By similarity). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (By similarity). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (PubMed:11268217). Binds to A/T-rich promoters (PubMed:11268217). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable). {ECO:0000250|UniProtKB:Q80VW7, ECO:0000269|PubMed:11268217, ECO:0000305}. |
| Q7Z591 | AKNA | S1206 | ochoa | Microtubule organization protein AKNA (AT-hook-containing transcription factor) | Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (By similarity). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (By similarity). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (By similarity). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (By similarity). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (PubMed:11268217). Binds to A/T-rich promoters (PubMed:11268217). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable). {ECO:0000250|UniProtKB:Q80VW7, ECO:0000269|PubMed:11268217, ECO:0000305}. |
| Q7Z5J4 | RAI1 | S578 | ochoa | Retinoic acid-induced protein 1 | Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}. |
| Q7Z5J4 | RAI1 | S776 | ochoa | Retinoic acid-induced protein 1 | Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}. |
| Q7Z5L9 | IRF2BP2 | S293 | ochoa | Interferon regulatory factor 2-binding protein 2 (IRF-2-binding protein 2) (IRF-2BP2) | Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities (PubMed:12799427). Represses the NFAT1-dependent transactivation of NFAT-responsive promoters (PubMed:21576369). Acts as a coactivator of VEGFA expression in cardiac and skeletal muscles (PubMed:20702774). Plays a role in immature B-cell differentiation (PubMed:27016798). {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:20702774, ECO:0000269|PubMed:21576369, ECO:0000269|PubMed:27016798}. |
| Q7Z6I6 | ARHGAP30 | S630 | ochoa | Rho GTPase-activating protein 30 (Rho-type GTPase-activating protein 30) | GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42. {ECO:0000269|PubMed:21565175}. |
| Q7Z6I8 | C5orf24 | S144 | ochoa | UPF0461 protein C5orf24 | None |
| Q7Z6J9 | TSEN54 | S76 | ochoa | tRNA-splicing endonuclease subunit Sen54 (SEN54 homolog) (HsSEN54) (tRNA-intron endonuclease Sen54) | Non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5' and 3' splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. {ECO:0000269|PubMed:15109492}. |
| Q7Z6M1 | RABEPK | S328 | ochoa | Rab9 effector protein with kelch motifs (40 kDa Rab9 effector protein) (p40) | Rab9 effector required for endosome to trans-Golgi network (TGN) transport. {ECO:0000269|PubMed:9230071}. |
| Q7Z6Z7 | HUWE1 | S927 | psp | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S1077 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S1861 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S2266 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S2362 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z736 | PLEKHH3 | S30 | ochoa | Pleckstrin homology domain-containing family H member 3 (PH domain-containing family H member 3) | None |
| Q7Z7A1 | CNTRL | S1103 | ochoa | Centriolin (Centrosomal protein 1) (Centrosomal protein of 110 kDa) (Cep110) | Involved in cell cycle progression and cytokinesis. During the late steps of cytokinesis, anchors exocyst and SNARE complexes at the midbody, thereby allowing secretory vesicle-mediated abscission. {ECO:0000269|PubMed:12732615, ECO:0000269|PubMed:16213214}. |
| Q86SQ0 | PHLDB2 | S58 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86SQ0 | PHLDB2 | S175 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86SQ0 | PHLDB2 | S281 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86T24 | ZBTB33 | S264 | ochoa | Transcriptional regulator Kaiso (Zinc finger and BTB domain-containing protein 33) | Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' and also binds to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. May contribute to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1 (PubMed:23251453). {ECO:0000269|PubMed:11445535, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:15548582, ECO:0000269|PubMed:15817151, ECO:0000269|PubMed:16354688, ECO:0000269|PubMed:23251453}. |
| Q86TB9 | PATL1 | S120 | ochoa | Protein PAT1 homolog 1 (PAT1-like protein 1) (Protein PAT1 homolog b) (Pat1b) (hPat1b) | RNA-binding protein involved in deadenylation-dependent decapping of mRNAs, leading to the degradation of mRNAs (PubMed:17936923, PubMed:20543818, PubMed:20584987, PubMed:20852261). Acts as a scaffold protein that connects deadenylation and decapping machinery (PubMed:17936923, PubMed:20543818, PubMed:20584987, PubMed:20852261). Required for cytoplasmic mRNA processing body (P-body) assembly (PubMed:17936923, PubMed:20543818, PubMed:20584987, PubMed:20852261). {ECO:0000269|PubMed:17936923, ECO:0000269|PubMed:20543818, ECO:0000269|PubMed:20584987, ECO:0000269|PubMed:20852261}.; FUNCTION: (Microbial infection) In case of infection, required for translation and replication of hepatitis C virus (HCV). {ECO:0000269|PubMed:19628699}. |
| Q86TC9 | MYPN | S613 | ochoa | Myopalladin (145 kDa sarcomeric protein) | Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines. {ECO:0000269|PubMed:11309420}. |
| Q86U86 | PBRM1 | S353 | ochoa | Protein polybromo-1 (hPB1) (BRG1-associated factor 180) (BAF180) (Polybromo-1D) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation. {ECO:0000269|PubMed:21248752, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q86UK7 | ZNF598 | S528 | ochoa | E3 ubiquitin-protein ligase ZNF598 (EC 2.3.2.27) (Zinc finger protein 598) | E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:32099016, PubMed:32579943, PubMed:33581075). ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs (PubMed:28065601, PubMed:28132843, PubMed:28685749). Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:30293783). Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10 (PubMed:28065601, PubMed:28132843, PubMed:28685749). Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides (PubMed:32099016, PubMed:32579943, PubMed:36302773). E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3 (PubMed:28685749). Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs (PubMed:22751931, PubMed:32726578). Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression (PubMed:29719242). {ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:28065601, ECO:0000269|PubMed:28132843, ECO:0000269|PubMed:28685749, ECO:0000269|PubMed:29719242, ECO:0000269|PubMed:30293783, ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:33581075, ECO:0000269|PubMed:36302773}.; FUNCTION: (Microbial infection) Required for poxvirus protein synthesis by mediating ubiquitination of RPS10/eS10 and RPS20/uS10 (PubMed:29719242). Poxvirus encoding mRNAs contain unusual 5' poly(A) leaders and ZNF598 is required for their translational efficiency, possibly via its ability to suppress readthrough or sliding on shorter poly(A) tracts (PubMed:29719242). {ECO:0000269|PubMed:29719242}. |
| Q86UK7 | ZNF598 | S572 | ochoa | E3 ubiquitin-protein ligase ZNF598 (EC 2.3.2.27) (Zinc finger protein 598) | E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:32099016, PubMed:32579943, PubMed:33581075). ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs (PubMed:28065601, PubMed:28132843, PubMed:28685749). Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:30293783). Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10 (PubMed:28065601, PubMed:28132843, PubMed:28685749). Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides (PubMed:32099016, PubMed:32579943, PubMed:36302773). E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3 (PubMed:28685749). Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs (PubMed:22751931, PubMed:32726578). Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression (PubMed:29719242). {ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:28065601, ECO:0000269|PubMed:28132843, ECO:0000269|PubMed:28685749, ECO:0000269|PubMed:29719242, ECO:0000269|PubMed:30293783, ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:33581075, ECO:0000269|PubMed:36302773}.; FUNCTION: (Microbial infection) Required for poxvirus protein synthesis by mediating ubiquitination of RPS10/eS10 and RPS20/uS10 (PubMed:29719242). Poxvirus encoding mRNAs contain unusual 5' poly(A) leaders and ZNF598 is required for their translational efficiency, possibly via its ability to suppress readthrough or sliding on shorter poly(A) tracts (PubMed:29719242). {ECO:0000269|PubMed:29719242}. |
| Q86UU1 | PHLDB1 | S47 | ochoa | Pleckstrin homology-like domain family B member 1 (Protein LL5-alpha) | None |
| Q86UU1 | PHLDB1 | S412 | ochoa | Pleckstrin homology-like domain family B member 1 (Protein LL5-alpha) | None |
| Q86UU1 | PHLDB1 | S1017 | ochoa | Pleckstrin homology-like domain family B member 1 (Protein LL5-alpha) | None |
| Q86UX7 | FERMT3 | S337 | ochoa | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86V15 | CASZ1 | S213 | ochoa | Zinc finger protein castor homolog 1 (Castor-related protein) (Putative survival-related protein) (Zinc finger protein 693) | Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}. |
| Q86V20 | SHLD2 | S70 | ochoa | Shieldin complex subunit 2 (Protein FAM35A) (RINN1-REV7-interacting novel NHEJ regulator 2) (Shield complex subunit 2) | Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893, PubMed:29789392). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893, PubMed:29789392). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). {ECO:0000269|PubMed:29656893, ECO:0000269|PubMed:29789392}. |
| Q86V21 | AACS | S412 | ochoa | Acetoacetyl-CoA synthetase (EC 6.2.1.16) (Acyl-CoA synthetase family member 1) (Protein sur-5 homolog) | Converts acetoacetate to acetoacetyl-CoA in the cytosol (By similarity). Ketone body-utilizing enzyme, responsible for the synthesis of cholesterol and fatty acids (By similarity). {ECO:0000250|UniProtKB:Q9D2R0, ECO:0000250|UniProtKB:Q9JMI1}. |
| Q86V48 | LUZP1 | S381 | ochoa | Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) | F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}. |
| Q86V81 | ALYREF | S94 | ochoa | THO complex subunit 4 (Tho4) (Ally of AML-1 and LEF-1) (Aly/REF export factor) (Transcriptional coactivator Aly/REF) (bZIP-enhancing factor BEF) | Functions as an mRNA export adapter; component of the transcription/export (TREX) complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602). Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B (PubMed:17984224). Plays a key role in mRNP recognition and mRNA packaging by bridging the mRNP-bound EJC and the TREX core complex (PubMed:37020021). TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1 (PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:37020021). Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC) (PubMed:15998806, PubMed:17984224, PubMed:37020021). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway) (PubMed:11675789, PubMed:11707413, PubMed:11979277, PubMed:15833825, PubMed:15998806, PubMed:17190602, PubMed:18364396, PubMed:22144908, PubMed:22893130, PubMed:23222130, PubMed:25662211). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim (PubMed:19165146). Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling (PubMed:28418038). Acts as a chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation (PubMed:10488337). Involved in transcription elongation and genome stability (PubMed:12438613). {ECO:0000269|PubMed:10488337, ECO:0000269|PubMed:11675789, ECO:0000269|PubMed:11707413, ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:17984224, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:19165146, ECO:0000269|PubMed:22144908, ECO:0000269|PubMed:22893130, ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:25662211, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:37020021}.; FUNCTION: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production; ALYREF/THOC4 mediates the recruitment of the TREX complex to the intronless viral mRNA. {ECO:0000269|PubMed:12438613, ECO:0000269|PubMed:18974867}. |
| Q86VF2 | IGFN1 | S446 | ochoa | Immunoglobulin-like and fibronectin type III domain-containing protein 1 (EEF1A2-binding protein 1) (KY-interacting protein 1) | None |
| Q86VF7 | NRAP | S437 | ochoa | Nebulin-related-anchoring protein (N-RAP) | May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. {ECO:0000250|UniProtKB:Q80XB4}. |
| Q86VH2 | KIF27 | S911 | ochoa | Kinesin-like protein KIF27 | Plays an essential role in motile ciliogenesis. {ECO:0000250}. |
| Q86VM9 | ZC3H18 | S34 | ochoa | Zinc finger CCCH domain-containing protein 18 (Nuclear protein NHN1) | None |
| Q86VR2 | RETREG3 | S313 | ochoa | Reticulophagy regulator 3 | Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (PubMed:33826365). Required for collagen quality control in a LIR motif-dependent manner (By similarity). Mediates NRF1-enhanced neurite outgrowth (PubMed:26040720). {ECO:0000250|UniProtKB:Q9CQV4, ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:33826365, ECO:0000269|PubMed:34338405}. |
| Q86VS8 | HOOK3 | S690 | ochoa | Protein Hook homolog 3 (h-hook3) (hHK3) | Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor (PubMed:25035494, PubMed:33734450). Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). May regulate clearance of endocytosed receptors such as MSR1. Participates in defining the architecture and localization of the Golgi complex. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). {ECO:0000250|UniProtKB:Q8BUK6, ECO:0000269|PubMed:11238449, ECO:0000269|PubMed:17237231, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:25035494, ECO:0000269|PubMed:32073997, ECO:0000269|PubMed:33734450}.; FUNCTION: (Microbial infection) May serve as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking. {ECO:0000305}. |
| Q86VW1 | SLC22A16 | S482 | ochoa | Solute carrier family 22 member 16 (Carnitine transporter 2) (CT2) (Fly-like putative transporter 2) (FLIPT2) (Flipt 2) (Organic cation transporter OKB1) (Organic cation/carnitine transporter 6) | Facilitative organic cation transporter that mediates the transport of carnitine as well as the polyamine spermidine (PubMed:12089149, PubMed:20037140). Mediates the partially Na(+)-dependent bidirectional transport of carnitine (PubMed:12089149). May mediate L-carnitine secretion from testis epididymal epithelium into the lumen which is involved in the maturation of spermatozoa (PubMed:12089149). {ECO:0000269|PubMed:12089149, ECO:0000269|PubMed:20037140}. |
| Q86VY9 | TMEM200A | S384 | ochoa | Transmembrane protein 200A | None |
| Q86W92 | PPFIBP1 | S936 | ochoa | Liprin-beta-1 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 1) (PTPRF-interacting protein-binding protein 1) (hSGT2) | May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}. |
| Q86WG5 | SBF2 | S1129 | ochoa | Myotubularin-related protein 13 (Inactive phosphatidylinositol 3-phosphatase 13) (SET-binding factor 2) | Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28 (PubMed:20937701, PubMed:25648148). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (PubMed:20937701, PubMed:25648148). In response to starvation-induced autophagy, activates RAB21 which in turn binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (PubMed:25648148). Acts as an adapter for the phosphatase MTMR2 (By similarity). Increases MTMR2 catalytic activity towards phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards phosphatidylinositol 3-phosphate (By similarity). {ECO:0000250|UniProtKB:E9PXF8, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:25648148}. |
| Q86WJ1 | CHD1L | S628 | ochoa | Chromodomain-helicase-DNA-binding protein 1-like (EC 3.6.4.-) (Amplified in liver cancer protein 1) | ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:33357431, PubMed:34210977, PubMed:34486521, PubMed:34874266). Recruited to DNA damage sites through interaction with poly-ADP-ribose: specifically recognizes and binds histones that are poly-ADP-ribosylated on serine residues in response to DNA damage (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:34486521, PubMed:34874266). Poly-ADP-ribose-binding activates the ATP-dependent chromatin remodeler activity, thereby regulating chromatin during DNA repair (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:34486521, PubMed:34874266). Catalyzes nucleosome sliding away from DNA breaks in an ATP-dependent manner (PubMed:19661379, PubMed:29220652, PubMed:29220653). Chromatin remodeling activity promotes PARP2 removal from chromatin (PubMed:33275888). {ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:29220652, ECO:0000269|PubMed:29220653, ECO:0000269|PubMed:33275888, ECO:0000269|PubMed:33357431, ECO:0000269|PubMed:34210977, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34874266}. |
| Q86XL3 | ANKLE2 | S339 | ochoa | Ankyrin repeat and LEM domain-containing protein 2 (LEM domain-containing protein 4) | Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit (PubMed:22770216). Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly (PubMed:22770216). May regulate nuclear localization of VRK1 in non-dividing cells (PubMed:31735666). It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex (PubMed:22770216). Involved in brain development (PubMed:25259927). {ECO:0000269|PubMed:22770216, ECO:0000269|PubMed:25259927, ECO:0000269|PubMed:31735666}. |
| Q86XZ4 | SPATS2 | S190 | ochoa | Spermatogenesis-associated serine-rich protein 2 (Serine-rich spermatocytes and round spermatid 59 kDa protein) (p59scr) | None |
| Q86YV0 | RASAL3 | S377 | ochoa | RAS protein activator like-3 | Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway. {ECO:0000250|UniProtKB:Q8C2K5}. |
| Q86YV0 | RASAL3 | S944 | ochoa | RAS protein activator like-3 | Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway. {ECO:0000250|UniProtKB:Q8C2K5}. |
| Q8IU85 | CAMK1D | S179 | ochoa | Calcium/calmodulin-dependent protein kinase type 1D (EC 2.7.11.17) (CaM kinase I delta) (CaM kinase ID) (CaM-KI delta) (CaMKI delta) (CaMKID) (CaMKI-like protein kinase) (CKLiK) | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta. {ECO:0000269|PubMed:11050006, ECO:0000269|PubMed:15840691, ECO:0000269|PubMed:16324104, ECO:0000269|PubMed:17056143}. |
| Q8IUD2 | ERC1 | S41 | ochoa | ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) | Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}. |
| Q8IUD2 | ERC1 | S82 | ochoa | ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) | Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}. |
| Q8IUD2 | ERC1 | S807 | ochoa | ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) | Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}. |
| Q8IV53 | DENND1C | S576 | ochoa | DENN domain-containing protein 1C (Connecdenn 3) (Protein FAM31C) | Guanine nucleotide exchange factor (GEF) which may activate RAB8A, RAB13 and RAB35. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}. |
| Q8IV61 | RASGRP3 | S597 | ochoa | Ras guanyl-releasing protein 3 (Calcium and DAG-regulated guanine nucleotide exchange factor III) (Guanine nucleotide exchange factor for Rap1) | Guanine nucleotide exchange factor (GEF) for Ras and Rap1. {ECO:0000269|PubMed:10934204}. |
| Q8IVF2 | AHNAK2 | S729 | ochoa | Protein AHNAK2 | None |
| Q8IVF2 | AHNAK2 | S2207 | ochoa | Protein AHNAK2 | None |
| Q8IVF2 | AHNAK2 | S2702 | ochoa | Protein AHNAK2 | None |
| Q8IVF5 | TIAM2 | S389 | ochoa | Rho guanine nucleotide exchange factor TIAM2 (SIF and TIAM1-like exchange factor) (T-lymphoma invasion and metastasis-inducing protein 2) (TIAM-2) | Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane (By similarity). Activates specifically RAC1, but not CDC42 and RHOA. {ECO:0000250, ECO:0000269|PubMed:10512681}. |
| Q8IVF5 | TIAM2 | S1565 | ochoa | Rho guanine nucleotide exchange factor TIAM2 (SIF and TIAM1-like exchange factor) (T-lymphoma invasion and metastasis-inducing protein 2) (TIAM-2) | Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane (By similarity). Activates specifically RAC1, but not CDC42 and RHOA. {ECO:0000250, ECO:0000269|PubMed:10512681}. |
| Q8IVL0 | NAV3 | S988 | ochoa | Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) | Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}. |
| Q8IVL0 | NAV3 | S1117 | ochoa | Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) | Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}. |
| Q8IVL1 | NAV2 | S1059 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IVL1 | NAV2 | S1264 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IVL1 | NAV2 | S1877 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IW35 | CEP97 | S728 | ochoa | Centrosomal protein of 97 kDa (Cep97) (Leucine-rich repeat and IQ domain-containing protein 2) | Acts as a key negative regulator of ciliogenesis in collaboration with CCP110 by capping the mother centriole thereby preventing cilia formation (PubMed:17719545, PubMed:30375385). Required for recruitment of CCP110 to the centrosome (PubMed:17719545). {ECO:0000269|PubMed:17719545, ECO:0000269|PubMed:30375385}. |
| Q8IW50 | FAM219A | S64 | ochoa | Protein FAM219A | None |
| Q8IW50 | FAM219A | S122 | ochoa | Protein FAM219A | None |
| Q8IWB9 | TEX2 | S538 | ochoa | Testis-expressed protein 2 (Transmembrane protein 96) | During endoplasmic reticulum (ER) stress or when cellular ceramide levels increase, may induce contacts between the ER and medial-Golgi complex to facilitate non-vesicular transport of ceramides from the ER to the Golgi complex where they are converted to complex sphingolipids, preventing toxic ceramide accumulation. {ECO:0000269|PubMed:28011845}. |
| Q8IWS0 | PHF6 | S120 | ochoa | PHD finger protein 6 (PHD-like zinc finger protein) | Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription. {ECO:0000269|PubMed:23229552}. |
| Q8IWT3 | CUL9 | S947 | ochoa | Cullin-9 (CUL-9) (UbcH7-associated protein 1) (p53-associated parkin-like cytoplasmic protein) | Core component of a Cul9-RING ubiquitin-protein ligase complex composed of CUL9 and RBX1 (PubMed:38605244). The CUL9-RBX1 complex mediates ubiquitination and subsequent degradation of BIRC5 and is required to maintain microtubule dynamics and genome integrity. Acts downstream of the 3M complex, which inhibits the ubiquitination of BIRC5 (PubMed:24793696). The CUL9-RBX1 complex also mediates mono-ubiquitination of p53/TP53 (PubMed:38605244). Acts as a cytoplasmic anchor protein in p53/TP53-associated protein complex. Regulates the subcellular localization of p53/TP53 and its subsequent function (PubMed:12526791, PubMed:17332328). Ubiquitinates apurinic/apyrimidinic endodeoxyribonuclease APEX2 (PubMed:38605244). Ubiquitination by the CUL9-RBX1 complex is predominantly mediated by E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2D2 (PubMed:38605244). {ECO:0000269|PubMed:12526791, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:24793696, ECO:0000269|PubMed:38605244}. |
| Q8IWT3 | CUL9 | S976 | ochoa | Cullin-9 (CUL-9) (UbcH7-associated protein 1) (p53-associated parkin-like cytoplasmic protein) | Core component of a Cul9-RING ubiquitin-protein ligase complex composed of CUL9 and RBX1 (PubMed:38605244). The CUL9-RBX1 complex mediates ubiquitination and subsequent degradation of BIRC5 and is required to maintain microtubule dynamics and genome integrity. Acts downstream of the 3M complex, which inhibits the ubiquitination of BIRC5 (PubMed:24793696). The CUL9-RBX1 complex also mediates mono-ubiquitination of p53/TP53 (PubMed:38605244). Acts as a cytoplasmic anchor protein in p53/TP53-associated protein complex. Regulates the subcellular localization of p53/TP53 and its subsequent function (PubMed:12526791, PubMed:17332328). Ubiquitinates apurinic/apyrimidinic endodeoxyribonuclease APEX2 (PubMed:38605244). Ubiquitination by the CUL9-RBX1 complex is predominantly mediated by E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2D2 (PubMed:38605244). {ECO:0000269|PubMed:12526791, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:24793696, ECO:0000269|PubMed:38605244}. |
| Q8IWU2 | LMTK2 | S525 | ochoa | Serine/threonine-protein kinase LMTK2 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase 2) (Brain-enriched kinase) (hBREK) (CDK5/p35-regulated kinase) (CPRK) (Kinase/phosphatase/inhibitor 2) (Lemur tyrosine kinase 2) (Serine/threonine-protein kinase KPI-2) | Phosphorylates PPP1C, phosphorylase b and CFTR. |
| Q8IWX8 | CHERP | S857 | ochoa | Calcium homeostasis endoplasmic reticulum protein (ERPROT 213-21) (SR-related CTD-associated factor 6) | Involved in calcium homeostasis, growth and proliferation. {ECO:0000269|PubMed:10794731, ECO:0000269|PubMed:12656674}. |
| Q8IWZ3 | ANKHD1 | S95 | ochoa | Ankyrin repeat and KH domain-containing protein 1 (HIV-1 Vpr-binding ankyrin repeat protein) (Multiple ankyrin repeats single KH domain) (hMASK) | May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}. |
| Q8IY22 | CMIP | S660 | ochoa | C-Maf-inducing protein (c-Mip) (Truncated c-Maf-inducing protein) (Tc-Mip) | Plays a role in T-cell signaling pathway. Isoform 2 may play a role in T-helper 2 (Th2) signaling pathway and seems to represent the first proximal signaling protein that links T-cell receptor-mediated signal to the activation of c-Maf Th2 specific factor. {ECO:0000269|PubMed:12939343, ECO:0000269|PubMed:15128042}. |
| Q8IY92 | SLX4 | S1631 | psp | Structure-specific endonuclease subunit SLX4 (BTB/POZ domain-containing protein 12) | Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks. {ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19596236}. |
| Q8IYT2 | CMTR2 | S424 | ochoa | Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 2 (EC 2.1.1.296) (Cap methyltransferase 2) (Cap2 2'O-ribose methyltransferase 2) (HMTr2) (MTr2) (FtsJ methyltransferase domain-containing protein 1) (Protein adrift homolog) | S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the second nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) (cap0) to produce m(7)GpppRmpNm (cap2). Recognizes a guanosine cap on RNA independently of its N(7) methylation status. Display cap2 methylation on both cap0 and cap1. Displays a preference for cap1 RNAs. {ECO:0000269|PubMed:21310715}. |
| Q8IYW5 | RNF168 | S237 | ochoa | E3 ubiquitin-protein ligase RNF168 (hRNF168) (EC 2.3.2.27) (RING finger protein 168) (RING-type E3 ubiquitin transferase RNF168) | E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively). {ECO:0000255|HAMAP-Rule:MF_03066, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22713238, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538}. |
| Q8IZD2 | KMT2E | S269 | ochoa | Inactive histone-lysine N-methyltransferase 2E (Inactive lysine N-methyltransferase 2E) (Myeloid/lymphoid or mixed-lineage leukemia protein 5) | Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:23798402, PubMed:24130829). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (PubMed:23798402, PubMed:24130829). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (By similarity). {ECO:0000250|UniProtKB:Q3UG20, ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:18573682, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.; FUNCTION: [Isoform NKp44L]: Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity. {ECO:0000269|PubMed:23958951}. |
| Q8IZQ1 | WDFY3 | S970 | ochoa | WD repeat and FYVE domain-containing protein 3 (Autophagy-linked FYVE protein) (Alfy) | Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (PubMed:27008544). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By similarity). After cytokinetic abscission, involved in midbody remnant degradation (PubMed:24128730). In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400). {ECO:0000250|UniProtKB:Q6VNB8, ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27008544}. |
| Q8N0S6 | CENPL | S53 | ochoa | Centromere protein L (CENP-L) (Interphase centromere complex protein 33) | Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. {ECO:0000269|PubMed:16716197}. |
| Q8N0Z3 | SPICE1 | S317 | ochoa | Spindle and centriole-associated protein 1 (Coiled-coil domain-containing protein 52) (Spindle and centriole-associated protein) | Regulator required for centriole duplication, for proper bipolar spindle formation and chromosome congression in mitosis. {ECO:0000269|PubMed:20736305}. |
| Q8N137 | CNTROB | S128 | ochoa | Centrobin (Centrosomal BRCA2-interacting protein) (LYST-interacting protein 8) | Required for centriole duplication. Inhibition of centriole duplication leading to defects in cytokinesis. {ECO:0000269|PubMed:16275750}. |
| Q8N163 | CCAR2 | S808 | ochoa|psp | Cell cycle and apoptosis regulator protein 2 (Cell division cycle and apoptosis regulator protein 2) (DBIRD complex subunit KIAA1967) (Deleted in breast cancer gene 1 protein) (DBC-1) (DBC.1) (NET35) (p30 DBC) | Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions (PubMed:22446626). Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis (PubMed:18235501, PubMed:18235502, PubMed:23352644). Inhibits SUV39H1 methyltransferase activity (PubMed:19218236). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:19131338). Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress (PubMed:23398316). Regulates the circadian expression of the core clock components NR1D1 and BMAL1 (PubMed:23398316). Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978). {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}. |
| Q8N1G0 | ZNF687 | S102 | ochoa | Zinc finger protein 687 | May be involved in transcriptional regulation. |
| Q8N1G0 | ZNF687 | S1106 | ochoa | Zinc finger protein 687 | May be involved in transcriptional regulation. |
| Q8N1G0 | ZNF687 | S1149 | ochoa | Zinc finger protein 687 | May be involved in transcriptional regulation. |
| Q8N1G4 | LRRC47 | S518 | ochoa | Leucine-rich repeat-containing protein 47 | None |
| Q8N201 | INTS1 | S1395 | ochoa | Integrator complex subunit 1 (Int1) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:25201415, PubMed:33243860, PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:33243860). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144, PubMed:26308897, PubMed:30737432). Within the integrator complex, INTS1 is involved in the post-termination step: INTS1 displaces INTS3 and the SOSS factors, allowing the integrator complex to return to the closed conformation, ready to bind to the paused elongation complex for another termination cycle (PubMed:38570683). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:25201415, ECO:0000269|PubMed:26308897, ECO:0000269|PubMed:30737432, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:38570683}. |
| Q8N257 | H2BC26 | S57 | ochoa | Histone H2B type 3-B (H2B type 12) (H2B-clustered histone 26) (H2B.U histone 1) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q8N2Y8 | RUSC2 | S913 | ochoa | AP-4 complex accessory subunit RUSC2 (Interacting protein of Rab1) (Iporin) (RUN and SH3 domain-containing protein 2) | Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network. {ECO:0000269|PubMed:30262884}. |
| Q8N302 | AGGF1 | S135 | ochoa | Angiogenic factor with G patch and FHA domains 1 (Angiogenic factor VG5Q) (hVG5Q) (G patch domain-containing protein 7) (Vasculogenesis gene on 5q protein) | Promotes angiogenesis and the proliferation of endothelial cells. Able to bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. {ECO:0000269|PubMed:14961121}. |
| Q8N3D4 | EHBP1L1 | S661 | ochoa | EH domain-binding protein 1-like protein 1 | May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000305|PubMed:27552051}. |
| Q8N3D4 | EHBP1L1 | S993 | ochoa | EH domain-binding protein 1-like protein 1 | May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000305|PubMed:27552051}. |
| Q8N468 | MFSD4A | S496 | ochoa | Major facilitator superfamily domain-containing protein 4A (Major facilitator superfamily domain-containing protein 4) | None |
| Q8N4C6 | NIN | S1157 | ochoa | Ninein (hNinein) (Glycogen synthase kinase 3 beta-interacting protein) (GSK3B-interacting protein) | Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15190203, PubMed:23386061). May also act as a centrosome maturation factor (PubMed:11956314). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15190203). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (PubMed:15190203). Required for centriole organization and microtubule anchoring at the mother centriole (PubMed:23386061). {ECO:0000269|PubMed:11956314, ECO:0000269|PubMed:15190203, ECO:0000269|PubMed:23386061}. |
| Q8N4C8 | MINK1 | S993 | ochoa | Misshapen-like kinase 1 (EC 2.7.11.1) (GCK family kinase MiNK) (MAPK/ERK kinase kinase kinase 6) (MEK kinase kinase 6) (MEKKK 6) (Misshapen/NIK-related kinase) (Mitogen-activated protein kinase kinase kinase kinase 6) | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking (PubMed:10708748, PubMed:16337592). Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons (By similarity). Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1 (PubMed:18930710, PubMed:21690388). Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1 (By similarity). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000250|UniProtKB:F1LP90, ECO:0000250|UniProtKB:Q9JM52, ECO:0000269|PubMed:10708748, ECO:0000269|PubMed:16337592, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. |
| Q8N4N8 | KIF2B | S616 | psp | Kinesin-like protein KIF2B | Plus end-directed microtubule-dependent motor required for spindle assembly and chromosome movement. Has microtubule depolymerization activity (PubMed:17538014). Plays a role in chromosome congression (PubMed:23891108). {ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:23891108}. |
| Q8N4S9 | MARVELD2 | S161 | ochoa | MARVEL domain-containing protein 2 (Tricellulin) | Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:17186462). {ECO:0000250|UniProtKB:Q3UZP0, ECO:0000269|PubMed:17186462}. |
| Q8N556 | AFAP1 | S510 | ochoa | Actin filament-associated protein 1 (110 kDa actin filament-associated protein) (AFAP-110) | Can cross-link actin filaments into both network and bundle structures (By similarity). May modulate changes in actin filament integrity and induce lamellipodia formation. May function as an adapter molecule that links other proteins, such as SRC and PKC to the actin cytoskeleton. Seems to play a role in the development and progression of prostate adenocarcinoma by regulating cell-matrix adhesions and migration in the cancer cells. {ECO:0000250, ECO:0000269|PubMed:15485829}. |
| Q8N5H3 | FAM89B | S37 | ochoa | Leucine repeat adapter protein 25 | Negatively regulates TGF-beta-induced signaling; in cooperation with SKI prevents the translocation of SMAD2 from the nucleus to the cytoplasm in response to TGF-beta. Acts as an adapter that mediates the specific recognition of LIMK1 by CDC42BPA and CDC42BPB in the lamellipodia. LRAP25-mediated CDC42BPA/CDC42BPB targeting to LIMK1 and the lamellipodium results in LIMK1 activation and the subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation. {ECO:0000250|UniProtKB:Q9QUI1}. |
| Q8N680 | ZBTB2 | S488 | ochoa | Zinc finger and BTB domain-containing protein 2 | May be involved in transcriptional regulation. |
| Q8N684 | CPSF7 | S322 | ochoa | Cleavage and polyadenylation specificity factor subunit 7 (Cleavage and polyadenylation specificity factor 59 kDa subunit) (CPSF 59 kDa subunit) (Cleavage factor Im complex 59 kDa subunit) (CFIm59) (Pre-mRNA cleavage factor Im 59 kDa subunit) | Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:17024186, PubMed:29276085, PubMed:8626397). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:17024186, PubMed:8626397). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF7 activates directly the mRNA 3'-processing machinery (PubMed:29276085). Binds to pA signals in RNA substrates (PubMed:17024186, PubMed:8626397). {ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:23187700, ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397}. |
| Q8N6T3 | ARFGAP1 | S174 | ochoa | ADP-ribosylation factor GTPase-activating protein 1 (ARF GAP 1) (ADP-ribosylation factor 1 GTPase-activating protein) (ARF1 GAP) (ARF1-directed GTPase-activating protein) | GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1). Involved in membrane trafficking and /or vesicle transport. Promotes hydrolysis of the ARF1-bound GTP and thus, is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles, a prerequisite for vesicle's fusion with target compartment. Probably regulates ARF1-mediated transport via its interaction with the KDELR proteins and TMED2. Overexpression induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, as when ARF1 is deactivated. Its activity is stimulated by phosphoinosides and inhibited by phosphatidylcholine (By similarity). {ECO:0000250}. |
| Q8N7H5 | PAF1 | S118 | ochoa | RNA polymerase II-associated factor 1 homolog (hPAF1) (Pancreatic differentiation protein 2) | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the RNF20/40 E3 ubiquitin-protein ligase complex. Involved in polyadenylation of mRNA precursors. Has oncogenic activity in vivo and in vitro. {ECO:0000269|PubMed:16491129, ECO:0000269|PubMed:19410543, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879, ECO:0000269|PubMed:22419161}. |
| Q8N8F7 | LSMEM1 | S38 | ochoa | Leucine-rich single-pass membrane protein 1 | None |
| Q8N8K9 | KIAA1958 | S249 | ochoa | Uncharacterized protein KIAA1958 | None |
| Q8N8R7 | ARL14EP | S183 | ochoa | ARL14 effector protein (ARF7 effector protein) | Through its interaction with ARL14 and MYO1E, may connect MHC class II-containing cytoplasmic vesicles to the actin network and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells. {ECO:0000269|PubMed:21458045}. |
| Q8N8U2 | CDYL2 | S163 | ochoa | Chromodomain Y-like protein 2 (CDY-like 2) | None |
| Q8N960 | CEP120 | S441 | ochoa | Centrosomal protein of 120 kDa (Cep120) (Coiled-coil domain-containing protein 100) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis (By similarity). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). {ECO:0000250|UniProtKB:Q7TSG1, ECO:0000269|PubMed:27185865}. |
| Q8N9T8 | KRI1 | S622 | ochoa | Protein KRI1 homolog | None |
| Q8NA03 | FSIP1 | S338 | ochoa | Fibrous sheath-interacting protein 1 | None |
| Q8NB90 | AFG2A | S279 | ochoa | ATPase family gene 2 protein homolog A (EC 3.6.4.10) (AFG2 AAA ATPase homolog A) (Ribosome biogenesis protein SPATA5) (Spermatogenesis-associated factor protein) (Spermatogenesis-associated protein 5) | ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity (PubMed:38554706). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024, PubMed:38554706). May be involved in morphological and functional mitochondrial transformations during spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q3UMC0, ECO:0000269|PubMed:35354024, ECO:0000269|PubMed:38554706}. |
| Q8NC51 | SERBP1 | S221 | ochoa | SERPINE1 mRNA-binding protein 1 (PAI1 RNA-binding protein 1) (PAI-RBP1) (Plasminogen activator inhibitor 1 RNA-binding protein) | Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:36691768). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (By similarity). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay (PubMed:11001948). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). {ECO:0000250|UniProtKB:Q9CY58, ECO:0000269|PubMed:11001948, ECO:0000269|PubMed:28695742, ECO:0000269|PubMed:36691768}. |
| Q8NCN4 | RNF169 | S539 | ochoa | E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) | Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}. |
| Q8NCN4 | RNF169 | S553 | ochoa | E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) | Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}. |
| Q8ND25 | ZNRF1 | S120 | ochoa | E3 ubiquitin-protein ligase ZNRF1 (EC 2.3.2.27) (Nerve injury-induced gene 283 protein) (RING-type E3 ubiquitin transferase ZNRF1) (Zinc/RING finger protein 1) | E3 ubiquitin-protein ligase that plays a role in different processes including cell differentiation, receptor recycling or regulation of inflammation (PubMed:28593998, PubMed:33996800, PubMed:37158982). Mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation (PubMed:22797923). Controls ligand-induced EGFR signaling via mediating receptor ubiquitination and recruitment of the ESCRT machinery (PubMed:33996800). Acts as a negative feedback mechanism controlling TLR3 trafficking by mediating TLR3 'Lys-63'-linked polyubiquitination to reduce type I IFN production (PubMed:37158982). Modulates inflammation by promoting caveolin-1/CAV1 ubiquitination and degradation to regulate TLR4-activated immune response (PubMed:28593998). {ECO:0000269|PubMed:22797923, ECO:0000269|PubMed:28593998, ECO:0000269|PubMed:29626159, ECO:0000269|PubMed:33996800, ECO:0000269|PubMed:37158982, ECO:0000305|PubMed:14561866}. |
| Q8NDF8 | TENT4B | S484 | ochoa | Terminal nucleotidyltransferase 4B (Non-canonical poly(A) RNA polymerase PAPD5) (EC 2.7.7.19) (PAP-associated domain-containing protein 5) (Terminal guanylyltransferase) (EC 2.7.7.-) (Terminal uridylyltransferase 3) (TUTase 3) (Topoisomerase-related function protein 4-2) (TRF4-2) | Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3' poly(A) tail creating a heterogeneous 3' poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation (PubMed:21788334, PubMed:30026317). Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Doesn't need a cofactor for polyadenylation activity (in vitro) (PubMed:21788334, PubMed:21855801). Required for cytoplasmic polyadenylation of mRNAs involved in carbohydrate metabolism, including the glucose transporter SLC2A1/GLUT1 (PubMed:28383716). Plays a role in replication-dependent histone mRNA degradation, probably through terminal uridylation of mature histone mRNAs. May play a role in sister chromatid cohesion (PubMed:18172165). Mediates 3' adenylation of the microRNA MIR21 followed by its 3'-to-5' trimming by the exoribonuclease PARN leading to degradation (PubMed:25049417). Mediates 3' adenylation of H/ACA box snoRNAs (small nucleolar RNAs) followed by its 3'-to-5' trimming by the exoribonuclease PARN which enhances snoRNA stability and maturation (PubMed:22442037). {ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:21788334, ECO:0000269|PubMed:21855801, ECO:0000269|PubMed:22442037, ECO:0000269|PubMed:25049417, ECO:0000269|PubMed:28383716, ECO:0000269|PubMed:30026317}. |
| Q8NDV7 | TNRC6A | S164 | ochoa | Trinucleotide repeat-containing gene 6A protein (CAG repeat protein 26) (EMSY interactor protein) (GW182 autoantigen) (Protein GW1) (Glycine-tryptophan protein of 182 kDa) | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As a scaffolding protein, associates with argonaute proteins bound to partially complementary mRNAs, and can simultaneously recruit CCR4-NOT and PAN deadenylase complexes. {ECO:0000269|PubMed:16284622, ECO:0000269|PubMed:16284623, ECO:0000269|PubMed:17596515, ECO:0000269|PubMed:17671087, ECO:0000269|PubMed:19056672, ECO:0000269|PubMed:19304925}. |
| Q8NE01 | CNNM3 | S688 | ochoa | Metal transporter CNNM3 (Ancient conserved domain-containing protein 3) (Cyclin-M3) | Probable metal transporter. {ECO:0000250}. |
| Q8NEF9 | SRFBP1 | S351 | ochoa | Serum response factor-binding protein 1 (SRF-dependent transcription regulation-associated protein) (p49/STRAP) | May be involved in regulating transcriptional activation of cardiac genes during the aging process. May play a role in biosynthesis and/or processing of SLC2A4 in adipose cells (By similarity). {ECO:0000250|UniProtKB:Q9CZ91}. |
| Q8NEJ9 | NGDN | S121 | ochoa | Neuroguidin (Centromere accumulated nuclear protein 1) (CANu1) (EIF4E-binding protein) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Its dissociation from the complex determines the transition from state pre-A1 to state pre-A1* (PubMed:34516797). Inhibits mRNA translation in a cytoplasmic polyadenylation element (CPE)-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q9DB96, ECO:0000269|PubMed:34516797}. |
| Q8NEM0 | MCPH1 | S254 | ochoa | Microcephalin | Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex. {ECO:0000269|PubMed:12046007, ECO:0000269|PubMed:15199523, ECO:0000269|PubMed:15220350}. |
| Q8NEV8 | EXPH5 | S238 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NEY1 | NAV1 | S528 | ochoa | Neuron navigator 1 (Pore membrane and/or filament-interacting-like protein 3) (Steerin-1) (Unc-53 homolog 1) (unc53H1) | May be involved in neuronal migration. {ECO:0000250}. |
| Q8NEY8 | PPHLN1 | S48 | ochoa | Periphilin-1 (CDC7 expression repressor) (CR) (Gastric cancer antigen Ga50) | Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is probably required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3. In the HUSH complex, contributes to the maintenance of the complex at chromatin (PubMed:26022416). Acts as a transcriptional corepressor and regulates the cell cycle, probably via the HUSH complex (PubMed:15474462, PubMed:17963697). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). May be involved in epithelial differentiation by contributing to epidermal integrity and barrier formation (PubMed:12853457). {ECO:0000269|PubMed:15474462, ECO:0000269|PubMed:17963697, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:30487602, ECO:0000305|PubMed:12853457}. |
| Q8NEZ5 | FBXO22 | S160 | psp | F-box only protein 22 (F-box protein FBX22p44) | Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that is implicated in the control of various cellular processes such as cell cycle control, transcriptional regulation, DNA damage repair, and apoptosis. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function. Acts as a key regulator of histone methylation marks namely H3K9 and H3K36 methylation through the regulation of histone demethylase KDM4A protein levels (PubMed:21768309). In complex with KDM4A, also regulates the abundance of TP53 by targeting methylated TP53 for degradation at the late senescent stage (PubMed:26868148). Under oxidative stress, promotes the ubiquitination and degradation of BACH1. Mechanistically, reactive oxygen species (ROS) covalently modify cysteine residues on the bZIP domain of BACH1, leading to its release from chromatin and making it accessible to FBXO22 (PubMed:39504958). Upon amino acid depletion, mediates 'Lys-27'-linked ubiquitination of MTOR and thereby inhibits substrate recruitment to mTORC1 (PubMed:37979583). Also inhibits SARS-CoV-2 replication by inducing NSP5 degradation (PubMed:39223933). {ECO:0000269|PubMed:21768309, ECO:0000269|PubMed:22972877, ECO:0000269|PubMed:26868148, ECO:0000269|PubMed:37979583, ECO:0000269|PubMed:39223933, ECO:0000269|PubMed:39504958}. |
| Q8NEZ5 | FBXO22 | S162 | psp | F-box only protein 22 (F-box protein FBX22p44) | Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that is implicated in the control of various cellular processes such as cell cycle control, transcriptional regulation, DNA damage repair, and apoptosis. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function. Acts as a key regulator of histone methylation marks namely H3K9 and H3K36 methylation through the regulation of histone demethylase KDM4A protein levels (PubMed:21768309). In complex with KDM4A, also regulates the abundance of TP53 by targeting methylated TP53 for degradation at the late senescent stage (PubMed:26868148). Under oxidative stress, promotes the ubiquitination and degradation of BACH1. Mechanistically, reactive oxygen species (ROS) covalently modify cysteine residues on the bZIP domain of BACH1, leading to its release from chromatin and making it accessible to FBXO22 (PubMed:39504958). Upon amino acid depletion, mediates 'Lys-27'-linked ubiquitination of MTOR and thereby inhibits substrate recruitment to mTORC1 (PubMed:37979583). Also inhibits SARS-CoV-2 replication by inducing NSP5 degradation (PubMed:39223933). {ECO:0000269|PubMed:21768309, ECO:0000269|PubMed:22972877, ECO:0000269|PubMed:26868148, ECO:0000269|PubMed:37979583, ECO:0000269|PubMed:39223933, ECO:0000269|PubMed:39504958}. |
| Q8NFA0 | USP32 | S1454 | ochoa | Ubiquitin carboxyl-terminal hydrolase 32 (EC 3.4.19.12) (Deubiquitinating enzyme 32) (Renal carcinoma antigen NY-REN-60) (Ubiquitin thioesterase 32) (Ubiquitin-specific-processing protease 32) | Deubiquitinase that can remove conjugated ubiquitin from target proteins, such as RAB7A and LAMTOR1 (PubMed:36476874). Acts as a positive regulator of the mTORC1 signaling by mediating deubiquitination of LAMTOR1, thereby promoting the association between LAMTOR1 and the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (PubMed:36476874). {ECO:0000269|PubMed:36476874}. |
| Q8NFC6 | BOD1L1 | S1077 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFC6 | BOD1L1 | S1124 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFG4 | FLCN | S406 | psp | Folliculin (BHD skin lesion fibrofolliculoma protein) (Birt-Hogg-Dube syndrome protein) | Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis (PubMed:17028174, PubMed:18663353, PubMed:21209915, PubMed:24081491, PubMed:24095279, PubMed:31672913, PubMed:31704029, PubMed:32612235, PubMed:34381247, PubMed:36103527, PubMed:37079666). GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:21209915, PubMed:24081491, PubMed:24095279, PubMed:24448649, PubMed:31672913, PubMed:31704029, PubMed:32612235, PubMed:36103527, PubMed:37079666). Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1 (PubMed:24095279, PubMed:31672913, PubMed:31704029, PubMed:32612235, PubMed:37079666). The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients (PubMed:31672913, PubMed:32612235). Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1 (PubMed:21209915, PubMed:24081491, PubMed:31672913, PubMed:32612235). In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, inactivates mTORC1 and maximizes nuclear translocation of TFEB and TFE3 (PubMed:31672913). Upon amino acid restimulation, RagA/RRAGA (or RagB/RRAGB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (PubMed:31672913). Indirectly acts as a positive regulator of Wnt signaling by promoting mTOR-dependent cytoplasmic retention of MiT/TFE factor TFE3 (PubMed:31272105). Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of TFE3, thereby increasing Wnt signaling (PubMed:30733432). Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of TFE3 (By similarity). Involved in the control of embryonic stem cells differentiation; together with LAMTOR1 it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (By similarity). In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia: may act by recruiting STK11/LKB1 to primary cilia for activation of AMPK resided at basal bodies, causing mTORC1 down-regulation (PubMed:27072130). Together with FNIP1 and/or FNIP2, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). Required for starvation-induced perinuclear clustering of lysosomes by promoting association of RILP with its effector RAB34 (PubMed:27113757). Regulates glycolysis by binding to lactate dehydrogenase LDHA, acting as an uncompetitive inhibitor (PubMed:34381247). {ECO:0000250|UniProtKB:Q8QZS3, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:21209915, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27072130, ECO:0000269|PubMed:27113757, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:31272105, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:31704029, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34381247, ECO:0000269|PubMed:36103527, ECO:0000269|PubMed:37079666}. |
| Q8NFP9 | NBEA | S1259 | ochoa | Neurobeachin (Lysosomal-trafficking regulator 2) (Protein BCL8B) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity). {ECO:0000250}. |
| Q8NFQ8 | TOR1AIP2 | S188 | ochoa | Torsin-1A-interacting protein 2 (Lumenal domain-like LAP1) | Required for endoplasmic reticulum integrity. Regulates the distribution of TOR1A between the endoplasmic reticulum and the nuclear envelope as well as induces TOR1A, TOR1B and TOR3A ATPase activity. {ECO:0000269|PubMed:19339278, ECO:0000269|PubMed:23569223, ECO:0000269|PubMed:24275647}. |
| Q8NFZ4 | NLGN2 | S718 | ochoa | Neuroligin-2 | Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Promotes clustering of postsynaptic LHFPL4 (By similarity). Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q69ZK9}. |
| Q8NFZ8 | CADM4 | S354 | ochoa | Cell adhesion molecule 4 (Immunoglobulin superfamily member 4C) (IgSF4C) (Nectin-like protein 4) (NECL-4) (TSLC1-like protein 2) | Involved in the cell-cell adhesion. Has calcium- and magnesium-independent cell-cell adhesion activity. May have tumor-suppressor activity. {ECO:0000269|PubMed:16261159}. |
| Q8NHM5 | KDM2B | S497 | ochoa | Lysine-specific demethylase 2B (EC 1.14.11.27) (CXXC-type zinc finger protein 2) (F-box and leucine-rich repeat protein 10) (F-box protein FBL10) (F-box/LRR-repeat protein 10) (JmjC domain-containing histone demethylation protein 1B) (Jumonji domain-containing EMSY-interactor methyltransferase motif protein) (Protein JEMMA) (Protein-containing CXXC domain 2) ([Histone-H3]-lysine-36 demethylase 1B) | Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}. |
| Q8NHV4 | NEDD1 | S468 | ochoa|psp | Protein NEDD1 (Neural precursor cell expressed developmentally down-regulated protein 1) (NEDD-1) | Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19509060}. |
| Q8TAD8 | SNIP1 | S200 | ochoa | Smad nuclear-interacting protein 1 (FHA domain-containing protein SNIP1) | Required for pre-mRNA splicing as component of the spliceosome (PubMed:29360106). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:11567019, ECO:0000269|PubMed:15378006, ECO:0000269|PubMed:18632581, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:29360106, ECO:0000305|PubMed:33509932}. |
| Q8TAP9 | MPLKIP | S124 | ochoa | M-phase-specific PLK1-interacting protein (TTD non-photosensitive 1 protein) | May play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis. {ECO:0000269|PubMed:17310276}. |
| Q8TB45 | DEPTOR | S19 | ochoa | DEP domain-containing mTOR-interacting protein (hDEPTOR) (DEP domain-containing protein 6) | Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes (PubMed:19446321, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:25936805, PubMed:29382726, PubMed:34519268, PubMed:34519269). DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy (PubMed:22017875, PubMed:22017876, PubMed:22017877). In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity (PubMed:34519268, PubMed:34519269). {ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:29382726, ECO:0000269|PubMed:34519268, ECO:0000269|PubMed:34519269}. |
| Q8TBA6 | GOLGA5 | S88 | ochoa | Golgin subfamily A member 5 (Cell proliferation-inducing gene 31 protein) (Golgin-84) (Protein Ret-II) (RET-fused gene 5 protein) | Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport. {ECO:0000269|PubMed:12538640, ECO:0000269|PubMed:15718469}. |
| Q8TBB5 | KLHDC4 | S407 | ochoa | Kelch domain-containing protein 4 | None |
| Q8TBC5 | ZSCAN18 | S349 | ochoa | Zinc finger and SCAN domain-containing protein 18 (Zinc finger protein 447) | May be involved in transcriptional regulation. |
| Q8TC05 | MDM1 | S648 | ochoa | Nuclear protein MDM1 | Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules (PubMed:26337392). {ECO:0000269|PubMed:26337392}. |
| Q8TCU6 | PREX1 | S1049 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein (P-Rex1) (PtdIns(3,4,5)-dependent Rac exchanger 1) | Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils. |
| Q8TCU6 | PREX1 | S1200 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein (P-Rex1) (PtdIns(3,4,5)-dependent Rac exchanger 1) | Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils. |
| Q8TD43 | TRPM4 | S839 | psp | Transient receptor potential cation channel subfamily M member 4 (hTRPM4) (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4) (Melastatin-4) | Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellular Ca(2+), it is impermeable to it (PubMed:12015988). Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane (PubMed:12015988). It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Plays a role in keratinocyte differentiation (PubMed:30528822). {ECO:0000269|PubMed:11535825, ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:12799367, ECO:0000269|PubMed:12842017, ECO:0000269|PubMed:14758478, ECO:0000269|PubMed:15121803, ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15472118, ECO:0000269|PubMed:15550671, ECO:0000269|PubMed:15590641, ECO:0000269|PubMed:15845551, ECO:0000269|PubMed:16186107, ECO:0000269|PubMed:16407466, ECO:0000269|PubMed:16424899, ECO:0000269|PubMed:16806463, ECO:0000269|PubMed:20625999, ECO:0000269|PubMed:20656926, ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:30528822}.; FUNCTION: [Isoform 2]: Lacks channel activity. {ECO:0000269|PubMed:12842017}. |
| Q8TE67 | EPS8L3 | S557 | ochoa | Epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8-like protein 3) (Epidermal growth factor receptor pathway substrate 8-related protein 3) (EPS8-related protein 3) | None |
| Q8TE77 | SSH3 | S85 | ochoa | Protein phosphatase Slingshot homolog 3 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 3) (SSH-3L) (hSSH-3L) | Protein phosphatase which may play a role in the regulation of actin filament dynamics. Can dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly (By similarity). {ECO:0000250}. |
| Q8TEC5 | SH3RF2 | S508 | ochoa | E3 ubiquitin-protein ligase SH3RF2 (EC 2.3.2.27) (Heart protein phosphatase 1-binding protein) (HEPP1) (POSH-eliminating RING protein) (Protein phosphatase 1 regulatory subunit 39) (RING finger protein 158) (RING-type E3 ubiquitin transferase SH3RF2) (SH3 domain-containing RING finger protein 2) | Has E3 ubiquitin-protein ligase activity (PubMed:24130170). Acts as an anti-apoptotic regulator of the JNK pathway by ubiquitinating and promoting the degradation of SH3RF1, a scaffold protein that is required for pro-apoptotic JNK activation (PubMed:22128169). Facilitates TNF-alpha-mediated recruitment of adapter proteins TRADD and RIPK1 to TNFRSF1A and regulates PAK4 protein stability via inhibition of its ubiquitin-mediated proteasomal degradation (PubMed:24130170). Inhibits PPP1CA phosphatase activity (PubMed:19389623, PubMed:19945436). {ECO:0000269|PubMed:19389623, ECO:0000269|PubMed:19945436, ECO:0000269|PubMed:22128169, ECO:0000269|PubMed:24130170}. |
| Q8TED9 | AFAP1L1 | S385 | ochoa | Actin filament-associated protein 1-like 1 (AFAP1-like protein 1) | May be involved in podosome and invadosome formation. {ECO:0000269|PubMed:21333378}. |
| Q8TEH3 | DENND1A | S619 | ochoa | DENN domain-containing protein 1A (Connecdenn 1) (Connecdenn) (Protein FAM31A) | Guanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Regulates clathrin-mediated endocytosis of synaptic vesicles and mediates exit from early endosomes (PubMed:20154091, PubMed:20937701). Binds phosphatidylinositol-phosphates (PtdInsPs), with some preference for PtdIns(3)P (By similarity). {ECO:0000250|UniProtKB:Q8K382, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}. |
| Q8TEJ3 | SH3RF3 | S797 | ochoa | E3 ubiquitin-protein ligase SH3RF3 (EC 2.3.2.27) (Plenty of SH3s 2) (SH3 domain-containing RING finger protein 3) (SH3 multiple domains protein 4) | Has E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20696164}. |
| Q8TEW0 | PARD3 | S380 | ochoa | Partitioning defective 3 homolog (PAR-3) (PARD-3) (Atypical PKC isotype-specific-interacting protein) (ASIP) (CTCL tumor antigen se2-5) (PAR3-alpha) | Adapter protein involved in asymmetrical cell division and cell polarization processes (PubMed:10954424, PubMed:27925688). Seems to play a central role in the formation of epithelial tight junctions (PubMed:27925688). Targets the phosphatase PTEN to cell junctions (By similarity). Involved in Schwann cell peripheral myelination (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (By similarity). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10934474). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (PubMed:19812038, PubMed:27925688). {ECO:0000250|UniProtKB:Q99NH2, ECO:0000250|UniProtKB:Q9Z340, ECO:0000269|PubMed:10934474, ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:27925688}. |
| Q8TF01 | PNISR | S393 | ochoa | Arginine/serine-rich protein PNISR (PNN-interacting serine/arginine-rich protein) (SR-related protein) (SR-rich protein) (Serine/arginine-rich-splicing regulatory protein 130) (SRrp130) (Splicing factor, arginine/serine-rich 130) (Splicing factor, arginine/serine-rich 18) | None |
| Q8TF40 | FNIP1 | S170 | ochoa | Folliculin-interacting protein 1 | Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491, PubMed:37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:37079666). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development (PubMed:32905580). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:32905580, ECO:0000269|PubMed:37079666}. |
| Q8TF40 | FNIP1 | S174 | ochoa | Folliculin-interacting protein 1 | Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491, PubMed:37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:37079666). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development (PubMed:32905580). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:32905580, ECO:0000269|PubMed:37079666}. |
| Q8WUD4 | CCDC12 | S149 | ochoa | Coiled-coil domain-containing protein 12 | None |
| Q8WUI4 | HDAC7 | S644 | ochoa | Histone deacetylase 7 (HD7) (EC 3.5.1.98) (Histone deacetylase 7A) (HD7a) (Protein deacetylase HDAC7) (EC 3.5.1.-) | Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (By similarity). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C (By similarity). During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene (PubMed:12239305). Positively regulates the transcriptional repressor activity of FOXP3 (PubMed:17360565). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). Also acetylates non-histone proteins, such as ALKBH5 (PubMed:37369679). {ECO:0000250|UniProtKB:Q8C2B3, ECO:0000269|PubMed:12239305, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:37369679}. |
| Q8WUM4 | PDCD6IP | S340 | ochoa | Programmed cell death 6-interacting protein (PDCD6-interacting protein) (ALG-2-interacting protein 1) (ALG-2-interacting protein X) (Hp95) | Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17556548, PubMed:17853893). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17556548, PubMed:17853893, PubMed:18641129). May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity). {ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129, ECO:0000269|PubMed:22660413}.; FUNCTION: (Microbial infection) Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function requires the interaction with CHMP4B. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as enveloped virus budding (HIV-1 and other lentiviruses). {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:18641129}. |
| Q8WUP2 | FBLIM1 | S285 | ochoa | Filamin-binding LIM protein 1 (FBLP-1) (Migfilin) (Mitogen-inducible 2-interacting protein) (MIG2-interacting protein) | Serves as an anchoring site for cell-ECM adhesion proteins and filamin-containing actin filaments. Is implicated in cell shape modulation (spreading) and motility. May participate in the regulation of filamin-mediated cross-linking and stabilization of actin filaments. May also regulate the assembly of filamin-containing signaling complexes that control actin assembly. Promotes dissociation of FLNA from ITGB3 and ITGB7. Promotes activation of integrins and regulates integrin-mediated cell-cell adhesion. {ECO:0000269|PubMed:12496242, ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18829455, ECO:0000269|PubMed:19074766}. |
| Q8WUX1 | SLC38A5 | S36 | ochoa | Sodium-coupled neutral amino acid transporter 5 (Solute carrier family 38 member 5) (System N transporter 2) | Symporter that cotransports neutral amino acids and sodium ions, coupled to an H(+) antiporter activity (PubMed:11243884). Releases L-glutamine and glycine from astroglial cells and may participate in the glutamate/GABA-L-glutamine cycle and the NMDA receptors activation (By similarity). In addition, contributes significantly to L-glutamine uptake in retina, namely in ganglion and Mueller cells therefore, participates in the retinal glutamate-glutamine cycle (By similarity). The transport activity is pH sensitive and Li(+) tolerant (PubMed:11243884). Moreover functions in both direction and is associated with large uncoupled fluxes of protons (By similarity). The transport is electroneutral coupled to the cotransport of 1 Na(+) and the antiport of 1 H(+) (By similarity). May have a particular importance for modulation of net hepatic glutamine flux (By similarity). {ECO:0000250|UniProtKB:A2VCW5, ECO:0000250|UniProtKB:Q3U1J0, ECO:0000269|PubMed:11243884}. |
| Q8WUY3 | PRUNE2 | S1613 | ochoa | Protein prune homolog 2 (BNIP2 motif-containing molecule at the C-terminal region 1) | May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. {ECO:0000269|PubMed:16288218}. |
| Q8WV41 | SNX33 | S61 | ochoa | Sorting nexin-33 (SH3 and PX domain-containing protein 3) | Plays a role in the reorganization of the cytoskeleton, endocytosis and cellular vesicle trafficking via its interactions with membranes, WASL, DNM1 and DNM2. Acts both during interphase and at the end of mitotic cell divisions. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Modulates endocytosis of cell-surface proteins, such as APP and PRNP; this then modulates the secretion of APP and PRNP peptides. Promotes membrane tubulation (in vitro). May promote the formation of macropinosomes. {ECO:0000269|PubMed:18353773, ECO:0000269|PubMed:18419754, ECO:0000269|PubMed:19487689, ECO:0000269|PubMed:20964629, ECO:0000269|PubMed:21048941, ECO:0000269|PubMed:22718350}. |
| Q8WVC0 | LEO1 | S110 | psp | RNA polymerase-associated protein LEO1 (Replicative senescence down-regulated leo1-like protein) | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling. {ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15791002, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742}. |
| Q8WVF1 | OSCP1 | S274 | ochoa | Protein OSCP1 (hOSCP1) (Organic solute transport protein 1) (Oxidored-nitro domain-containing protein 1) | May be involved in drug clearance in the placenta. {ECO:0000269|PubMed:16006562}. |
| Q8WWH5 | TRUB1 | S134 | ochoa | Pseudouridylate synthase TRUB1 (EC 5.4.99.-) (TruB pseudouridine synthase homolog 1) (tRNA pseudouridine 55 synthase TRUB1) (Psi55 synthase TRUB1) (EC 5.4.99.25) | Pseudouridine synthase that catalyzes pseudouridylation of mRNAs and tRNAs (PubMed:28073919, PubMed:31477916, PubMed:32926445). Mediates pseudouridylation of mRNAs with the consensus sequence 5'-GUUCNANNC-3', harboring a stem-loop structure (PubMed:28073919, PubMed:31477916). Constitutes the major pseudouridine synthase acting on mRNAs (PubMed:28073919). Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs (PubMed:32926445, PubMed:33023933). Promotes the processing of pri-let-7 microRNAs (pri-miRNAs) independently of its RNA pseudouridylate synthase activity (PubMed:32926445). Acts by binding to the stem-loop structure on pri-let-7, preventing LIN28-binding (LIN28A and/or LIN28B), thereby enhancing the interaction between pri-let-7 and the microprocessor DGCR8, which mediates miRNA maturation (PubMed:32926445). {ECO:0000269|PubMed:28073919, ECO:0000269|PubMed:31477916, ECO:0000269|PubMed:32926445, ECO:0000269|PubMed:33023933}. |
| Q8WWI1 | LMO7 | S919 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWI1 | LMO7 | S1204 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWI1 | LMO7 | S1653 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWL2 | SPIRE2 | S371 | ochoa | Protein spire homolog 2 (Spir-2) | Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning and asymmetric cell division during meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). {ECO:0000250|UniProtKB:Q8K1S6, ECO:0000269|PubMed:21620703, ECO:0000269|PubMed:26287480}. |
| Q8WWL2 | SPIRE2 | S387 | ochoa | Protein spire homolog 2 (Spir-2) | Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning and asymmetric cell division during meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). {ECO:0000250|UniProtKB:Q8K1S6, ECO:0000269|PubMed:21620703, ECO:0000269|PubMed:26287480}. |
| Q8WWY3 | PRPF31 | S439 | ochoa | U4/U6 small nuclear ribonucleoprotein Prp31 (Pre-mRNA-processing factor 31) (Serologically defined breast cancer antigen NY-BR-99) (U4/U6 snRNP 61 kDa protein) (Protein 61K) (hPrp31) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11867543, PubMed:20118938, PubMed:28781166). Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:11867543). {ECO:0000269|PubMed:11867543, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:28781166}. |
| Q8WXG6 | MADD | S1270 | ochoa | MAP kinase-activating death domain protein (Differentially expressed in normal and neoplastic cells) (Insulinoma glucagonoma clone 20) (Rab3 GDP/GTP exchange factor) (RabGEF) (Rab3 GDP/GTP exchange protein) (Rab3GEP) | Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064). {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q80U28, ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:32761064, ECO:0000269|PubMed:9115275}. |
| Q8WY91 | THAP4 | S186 | ochoa | Peroxynitrite isomerase THAP4 (EC 5.99.-.-) (Ferric Homo sapiens nitrobindin) (Hs-Nb(III)) (THAP domain-containing protein 4) | Heme-binding protein able to scavenge peroxynitrite and to protect free L-tyrosine against peroxynitrite-mediated nitration, by acting as a peroxynitrite isomerase that converts peroxynitrite to nitrate. Therefore, this protein likely plays a role in peroxynitrite sensing and in the detoxification of reactive nitrogen and oxygen species (RNS and ROS, respectively). Is able to bind nitric oxide (NO) in vitro, but may act as a sensor of peroxynitrite levels in vivo, possibly modulating the transcriptional activity residing in the N-terminal region. {ECO:0000269|PubMed:30524950, ECO:0000269|PubMed:32295384}. |
| Q8WYL5 | SSH1 | S984 | ochoa | Protein phosphatase Slingshot homolog 1 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 1) (SSH-1L) (hSSH-1L) | Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. {ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12684437, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:14531860, ECO:0000269|PubMed:14645219, ECO:0000269|PubMed:15056216, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:16230460}. |
| Q92545 | TMEM131 | S1202 | ochoa | Transmembrane protein 131 (Protein RW1) | Collagen binding transmembrane protein involved in collagen secretion by recruiting the ER-to-Golgi transport complex TRAPPIII (PubMed:32095531). May play a role in the immune response to viral infection. {ECO:0000250, ECO:0000269|PubMed:32095531}. |
| Q92545 | TMEM131 | S1515 | ochoa | Transmembrane protein 131 (Protein RW1) | Collagen binding transmembrane protein involved in collagen secretion by recruiting the ER-to-Golgi transport complex TRAPPIII (PubMed:32095531). May play a role in the immune response to viral infection. {ECO:0000250, ECO:0000269|PubMed:32095531}. |
| Q92547 | TOPBP1 | S370 | ochoa | DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1) | Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493, PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:33592542, PubMed:35597237, PubMed:37674080). Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations (PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:35597237, PubMed:37674080). Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites (PubMed:30898438, PubMed:35597237, PubMed:37674080). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase (PubMed:37674080). Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair (PubMed:37674080). Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex (PubMed:31135337). In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression (PubMed:16530042, PubMed:21777809). Acts as an activator of the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei (PubMed:35121901, PubMed:35842428, PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage (PubMed:12697828, PubMed:15075294). {ECO:0000250|UniProtKB:Q800K6, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. |
| Q92604 | LPGAT1 | S233 | ochoa | Acyl-CoA:lysophosphatidylglycerol acyltransferase 1 (2-acylglycerophosphocholine O-acyltransferase) (EC 2.3.1.62) (Acyl-CoA:monoacylglycerol acyltransferase LPGAT1) (EC 2.3.1.22) (Lysophospholipid acyltransferase 7) (LPLAT7) (EC 2.3.1.-) (Stearoyl-CoA:1-lyso-2-acyl-PE acyltransferase) | Lysophospholipid acyltransferase involved in fatty acyl chain remodeling of glycerophospholipids in the endoplasmic reticulum membrane (By similarity). Selectively catalyzes the transfer and esterification of saturated long-chain fatty acids from acyl-CoA to the sn-1 position of 1-lyso-2-acyl phosphatidylethanolamines (1-lyso-PE, LPE), with a preference for stearoyl CoA over palmitoyl CoA as acyl donor (PubMed:36049524). Acts in concert with an unknown phospholipase A1 to convert palmitate phosphatidylethanolamine (PE) species into stearate ones. Provides substrates to the PE methylation pathway, controlling stearate/palmitate composition of PE and phosphatidylcholine (PC) species with an overall impact on de novo hepatic lipid synthesis, body fat content and life span (By similarity). Can acylate lysophosphatidylglycerols (LPG) using various saturated fatty acyl-CoAs as acyl donors (PubMed:15485873). Can also acylate monoacylglycerols with a preference for 2-monoacylglycerols over 1-monoacylglycerols (By similarity). Has no activity toward lysophosphatidic acids (LPA) (By similarity). {ECO:0000250|UniProtKB:Q91YX5, ECO:0000269|PubMed:15485873, ECO:0000269|PubMed:36049524}. |
| Q92608 | DOCK2 | S1731 | ochoa | Dedicator of cytokinesis protein 2 | Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2. {ECO:0000269|PubMed:21613211}. |
| Q92610 | ZNF592 | S1021 | ochoa | Zinc finger protein 592 | May be involved in transcriptional regulation. {ECO:0000269|PubMed:20531441}. |
| Q92614 | MYO18A | S234 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92616 | GCN1 | S1412 | ochoa | Stalled ribosome sensor GCN1 (GCN1 eIF-2-alpha kinase activator homolog) (GCN1-like protein 1) (General control of amino-acid synthesis 1-like protein 1) (Translational activator GCN1) (HsGCN1) | Ribosome collision sensor that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (PubMed:32610081, PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Directly binds to the ribosome and acts as a sentinel for colliding ribosomes: activated following ribosome stalling and promotes recruitment of RNF14, which directly ubiquitinates EEF1A1/eEF1A, leading to its degradation (PubMed:36638793, PubMed:37951215, PubMed:37951216). In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein (PubMed:36638793, PubMed:37651229). GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of EIF2AK4/GCN2 in response to amino acid starvation (By similarity). Interaction with EIF2AK4/GCN2 on translating ribosomes stimulates EIF2AK4/GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) (By similarity). EIF2S1/eIF-2-alpha phosphorylation converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity). {ECO:0000250|UniProtKB:E9PVA8, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229, ECO:0000269|PubMed:37951215, ECO:0000269|PubMed:37951216}. |
| Q92630 | DYRK2 | S449 | psp | Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC 2.7.12.1) | Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}. |
| Q92633 | LPAR1 | S341 | ochoa | Lysophosphatidic acid receptor 1 (LPA receptor 1) (LPA-1) (Lysophosphatidic acid receptor Edg-2) | Receptor for lysophosphatidic acid (LPA) (PubMed:19306925, PubMed:25025571, PubMed:26091040, PubMed:9070858). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels (PubMed:26091040). Signaling triggers an increase of cytoplasmic Ca(2+) levels (PubMed:19656035, PubMed:19733258, PubMed:26091040). Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate (PubMed:19306925). Signaling mediates activation of down-stream MAP kinases (By similarity). Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction (PubMed:26091040). Promotes the activation of Rho and the formation of actin stress fibers (PubMed:26091040). Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1 (By similarity). Through its function as LPA receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding (PubMed:18066075, PubMed:19656035, PubMed:19733258). Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to LPA (By similarity). Inhibits the intracellular ciliogenesis pathway in response to LPA and through AKT1 activation (PubMed:31204173). Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain (By similarity). {ECO:0000250|UniProtKB:P61793, ECO:0000269|PubMed:18066075, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:19656035, ECO:0000269|PubMed:19733258, ECO:0000269|PubMed:25025571, ECO:0000269|PubMed:26091040, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:9070858, ECO:0000305|PubMed:11093753, ECO:0000305|PubMed:9069262}. |
| Q92667 | AKAP1 | S600 | ochoa | A-kinase anchor protein 1, mitochondrial (A-kinase anchor protein 149 kDa) (AKAP 149) (Dual specificity A-kinase-anchoring protein 1) (D-AKAP-1) (Protein kinase A-anchoring protein 1) (PRKA1) (Spermatid A-kinase anchor protein 84) (S-AKAP84) | Binds to type I and II regulatory subunits of protein kinase A and anchors them to the cytoplasmic face of the mitochondrial outer membrane (By similarity). Involved in mitochondrial-mediated antiviral innate immunity (PubMed:31522117). Promotes translocation of NDUFS1 into mitochondria to regulate mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) activity (By similarity). {ECO:0000250|UniProtKB:O08715, ECO:0000269|PubMed:31522117}. |
| Q92777 | SYN2 | S341 | ochoa | Synapsin-2 (Synapsin II) | Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. May play a role in noradrenaline secretion by sympathetic neurons (By similarity). {ECO:0000250}. |
| Q92785 | DPF2 | S117 | ochoa | Zinc finger protein ubi-d4 (Apoptosis response zinc finger protein) (BRG1-associated factor 45D) (BAF45D) (D4, zinc and double PHD fingers family 2) (Protein requiem) | Plays an active role in transcriptional regulation by binding modified histones H3 and H4 (PubMed:27775714, PubMed:28533407). Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells (PubMed:28533407). Might also have a role in the development and maturation of lymphoid cells (By similarity). Involved in the regulation of non-canonical NF-kappa-B pathway (PubMed:20460684). {ECO:0000250|UniProtKB:Q61103, ECO:0000269|PubMed:20460684, ECO:0000269|PubMed:27775714, ECO:0000269|PubMed:28533407}. |
| Q92830 | KAT2A | S307 | psp | Histone acetyltransferase KAT2A (EC 2.3.1.48) (General control of amino acid synthesis protein 5-like 2) (Histone acetyltransferase GCN5) (hGCN5) (Histone glutaryltransferase KAT2A) (EC 2.3.1.-) (Histone succinyltransferase KAT2A) (EC 2.3.1.-) (Lysine acetyltransferase 2A) (STAF97) | Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context (PubMed:29211711, PubMed:35995428). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755, PubMed:21131905). Has a a strong preference for acetylation of H3 at 'Lys-9' (H3K9ac) (PubMed:21131905). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (PubMed:29973595, PubMed:31527837). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (By similarity). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC) pluripotency and differentiation (By similarity). Also acetylates non-histone proteins, such as CEBPB, MRE11, PPARGC1A, PLK4 and TBX5 (PubMed:16753578, PubMed:17301242, PubMed:27796307, PubMed:29174768, PubMed:38128537). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A (PubMed:16753578, PubMed:23142079). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (PubMed:31542297). {ECO:0000250|UniProtKB:Q9JHD2, ECO:0000269|PubMed:16753578, ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837, ECO:0000269|PubMed:31542297, ECO:0000269|PubMed:35995428, ECO:0000269|PubMed:38128537}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. {ECO:0000269|PubMed:11384967}. |
| Q92879 | CELF1 | S241 | psp | CUGBP Elav-like family member 1 (CELF-1) (50 kDa nuclear polyadenylated RNA-binding protein) (Bruno-like protein 2) (CUG triplet repeat RNA-binding protein 1) (CUG-BP1) (CUG-BP- and ETR-3-like factor 1) (Deadenylation factor CUG-BP) (Embryo deadenylation element-binding protein homolog) (EDEN-BP homolog) (RNA-binding protein BRUNOL-2) | RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Acts both as an activator and as a repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Activates SM exon 5 inclusion by antagonizing the repressive effect of PTB. Promotes exclusion of exon 11 of the INSR pre-mRNA. Inhibits, together with HNRNPH1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Increases translation and controls the choice of translation initiation codon of CEBPB mRNA. Increases mRNA translation of CEBPB in aging liver (By similarity). Increases translation of CDKN1A mRNA by antagonizing the repressive effect of CALR3. Mediates rapid cytoplasmic mRNA deadenylation. Recruits the deadenylase PARN to the poly(A) tail of EDEN-containing mRNAs to promote their deadenylation. Required for completion of spermatogenesis (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK and to Bruno response elements (BREs). Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA. Binds to AU-rich sequences (AREs or EDEN-like) localized in the 3'-UTR of JUN and FOS mRNAs. Binds to the IR RNA. Binds to the 5'-region of CDKN1A and CEBPB mRNAs. Binds with the 5'-region of CEBPB mRNA in aging liver. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF2, negatively regulates the processing to mature miRNA (PubMed:28431233). {ECO:0000250, ECO:0000269|PubMed:10536163, ECO:0000269|PubMed:11124939, ECO:0000269|PubMed:11158314, ECO:0000269|PubMed:12649496, ECO:0000269|PubMed:12799066, ECO:0000269|PubMed:14726956, ECO:0000269|PubMed:16601207, ECO:0000269|PubMed:16946708, ECO:0000269|PubMed:28431233}. |
| Q92888 | ARHGEF1 | S240 | psp | Rho guanine nucleotide exchange factor 1 (115 kDa guanine nucleotide exchange factor) (p115-RhoGEF) (p115RhoGEF) (Sub1.5) | Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits (PubMed:9641915, PubMed:9641916). Acts as a GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase (PubMed:30521495, PubMed:8810315, PubMed:9641915, PubMed:9641916). Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain (PubMed:9641916). This GEF activity is inhibited by binding to activated GNA12 (PubMed:9641916). Mediates angiotensin-2-induced RhoA activation (PubMed:20098430). In lymphoid follicles, may trigger activation of GNA13 as part of S1PR2-dependent signaling pathway that leads to inhibition of germinal center (GC) B cell growth and migration outside the GC niche. {ECO:0000250|UniProtKB:Q61210, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:30521495, ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9641915, ECO:0000269|PubMed:9641916}. |
| Q92905 | COPS5 | S284 | ochoa | COP9 signalosome complex subunit 5 (SGN5) (Signalosome subunit 5) (EC 3.4.-.-) (Jun activation domain-binding protein 1) | Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:9535219}. |
| Q92917 | GPKOW | S20 | ochoa | G-patch domain and KOW motifs-containing protein (G-patch domain-containing protein 5) (Protein MOS2 homolog) (Protein T54) | RNA-binding protein involved in pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:25296192, ECO:0000305|PubMed:33509932}. |
| Q92945 | KHSRP | S274 | ochoa|psp | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q92966 | SNAPC3 | S74 | ochoa | snRNA-activating protein complex subunit 3 (SNAPc subunit 3) (Proximal sequence element-binding transcription factor subunit beta) (PSE-binding factor subunit beta) (PTF subunit beta) (Small nuclear RNA-activating complex polypeptide 3) (snRNA-activating protein complex 50 kDa subunit) (SNAPc 50 kDa subunit) | Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box. {ECO:0000269|PubMed:12621023}. |
| Q92994 | BRF1 | S392 | ochoa | Transcription factor IIIB 90 kDa subunit (TFIIIB90) (hTFIIIB90) (B-related factor 1) (BRF-1) (hBRF) (TAF3B2) (TATA box-binding protein-associated factor, RNA polymerase III, subunit 2) | General activator of RNA polymerase which utilizes different TFIIIB complexes at structurally distinct promoters. The isoform 1 is involved in the transcription of tRNA, adenovirus VA1, 7SL and 5S RNA. Isoform 2 is required for transcription of the U6 promoter. |
| Q92995 | USP13 | S466 | ochoa | Ubiquitin carboxyl-terminal hydrolase 13 (EC 3.4.19.12) (Deubiquitinating enzyme 13) (Isopeptidase T-3) (ISOT-3) (Ubiquitin thioesterase 13) (Ubiquitin-specific-processing protease 13) | Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response (PubMed:21571647, PubMed:32772043, PubMed:33592542). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy (PubMed:32101753). Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB (PubMed:32772043). In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1 (PubMed:33592542). Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion (PubMed:36585612). Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1 (PubMed:23940278, PubMed:28534493). {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:32101753, ECO:0000269|PubMed:32772043, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:36585612}. |
| Q92997 | DVL3 | S48 | ochoa|psp | Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) | Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}. |
| Q92997 | DVL3 | S311 | psp | Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) | Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}. |
| Q92997 | DVL3 | S512 | psp | Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) | Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}. |
| Q93079 | H2BC9 | S57 | ochoa | Histone H2B type 1-H (H2B-clustered histone 9) (Histone H2B.j) (H2B/j) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q93100 | PHKB | S27 | ochoa | Phosphorylase b kinase regulatory subunit beta (Phosphorylase kinase subunit beta) | Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation. |
| Q969F1 | GTF3C6 | S174 | ochoa | General transcription factor 3C polypeptide 6 (Transcription factor IIIC 35 kDa subunit) (TFIIIC 35 kDa subunit) (TFIIIC35) (Transcription factor IIIC subunit 6) | Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters. {ECO:0000269|PubMed:17409385}. |
| Q969G9 | NKD1 | S242 | ochoa | Protein naked cuticle homolog 1 (Naked-1) (hNkd) (hNkd1) | Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity. {ECO:0000269|PubMed:11752446, ECO:0000269|PubMed:15687260, ECO:0000269|PubMed:16567647}. |
| Q969H4 | CNKSR1 | S568 | ochoa | Connector enhancer of kinase suppressor of ras 1 (Connector enhancer of KSR 1) (CNK homolog protein 1) (CNK1) (hCNK1) (Connector enhancer of KSR-like) | May function as an adapter protein or regulator of Ras signaling pathways. |
| Q969J2 | ZKSCAN4 | S184 | ochoa | Zinc finger protein with KRAB and SCAN domains 4 (P373c6.1) (Zinc finger protein 307) (Zinc finger protein 427) | May be involved in the transcriptional activation of MDM2 and EP300 genes. {ECO:0000269|PubMed:17910948}. |
| Q969R5 | L3MBTL2 | S83 | ochoa | Lethal(3)malignant brain tumor-like protein 2 (H-l(3)mbt-like protein 2) (L(3)mbt-like protein 2) | Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Its association with a chromatin-remodeling complex suggests that it may contribute to prevent expression of genes that trigger the cell into mitosis. Binds to monomethylated and dimethylated 'Lys-20' on histone H4. Binds histone H3 peptides that are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27'. {ECO:0000269|PubMed:19233876}. |
| Q969W3 | VCF1 | S144 | ochoa | Protein VCF1 (VCP nuclear cofactor family member 1) | None |
| Q969Z4 | RELT | S208 | ochoa | Tumor necrosis factor receptor superfamily member 19L (Receptor expressed in lymphoid tissues) | May play a role in apoptosis (PubMed:19969290, PubMed:28688764). Induces activation of MAPK14/p38 and MAPK8/JNK MAPK cascades, when overexpressed (PubMed:16530727). Involved in dental enamel formation (PubMed:30506946). {ECO:0000269|PubMed:16530727, ECO:0000269|PubMed:19969290, ECO:0000269|PubMed:28688764, ECO:0000269|PubMed:30506946}. |
| Q96A08 | H2BC1 | S58 | ochoa | Histone H2B type 1-A (Histone H2B, testis) (TSH2B.1) (hTSH2B) (Testis-specific histone H2B) | Variant histone specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells (By similarity). Entirely replaces classical histone H2B prior nucleosome to protamine transition and probably acts as a nucleosome dissociating factor that creates a more dynamic chromatin, facilitating the large-scale exchange of histones (By similarity). Core component of nucleosome (By similarity). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template (By similarity). Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (By similarity). DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling (By similarity). Also found in fat cells, its function and the presence of post-translational modifications specific to such cells are still unclear (PubMed:21249133). {ECO:0000250|UniProtKB:P70696, ECO:0000269|PubMed:21249133}. |
| Q96AC1 | FERMT2 | S175 | ochoa|psp | Fermitin family homolog 2 (Kindlin-2) (Mitogen-inducible gene 2 protein) (MIG-2) (Pleckstrin homology domain-containing family C member 1) (PH domain-containing family C member 1) | Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling. {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155, ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}. |
| Q96AM1 | MRGPRF | S326 | ochoa | Mas-related G-protein coupled receptor member F (Mas-related gene F protein) (G-protein coupled receptor 140) (G-protein coupled receptor 168) | Orphan receptor. May bind to a neuropeptide and may regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). {ECO:0000250}. |
| Q96AQ6 | PBXIP1 | S72 | ochoa | Pre-B-cell leukemia transcription factor-interacting protein 1 (Hematopoietic PBX-interacting protein) | Regulator of pre-B-cell leukemia transcription factors (BPXs) function. Inhibits the binding of PBX1-HOX complex to DNA and blocks the transcriptional activity of E2A-PBX1. Tethers estrogen receptor-alpha (ESR1) to microtubules and allows them to influence estrogen receptors-alpha signaling. {ECO:0000269|PubMed:10825160, ECO:0000269|PubMed:12360403, ECO:0000269|PubMed:17043237}. |
| Q96B97 | SH3KBP1 | S181 | ochoa | SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) | Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}. |
| Q96BY6 | DOCK10 | S1232 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96BY6 | DOCK10 | S1236 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96CB8 | INTS12 | S350 | ochoa | Integrator complex subunit 12 (Int12) (PHD finger protein 22) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:38570683}. |
| Q96D09 | GPRASP2 | S542 | ochoa | G-protein coupled receptor-associated sorting protein 2 (GASP-2) | May play a role in regulation of a variety of G-protein coupled receptors. {ECO:0000269|PubMed:15086532}. |
| Q96DF8 | ESS2 | S446 | ochoa | Splicing factor ESS-2 homolog (DiGeorge syndrome critical region 13) (DiGeorge syndrome critical region 14) (DiGeorge syndrome protein H) (DGS-H) (Protein ES2) | May be involved in pre-mRNA splicing. {ECO:0000250|UniProtKB:P34420}. |
| Q96DR7 | ARHGEF26 | S296 | ochoa | Rho guanine nucleotide exchange factor 26 (SH3 domain-containing guanine exchange factor) | Activates RhoG GTPase by promoting the exchange of GDP by GTP. Required for the formation of membrane ruffles during macropinocytosis. Required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB, which induces cytoskeleton rearrangements and promotes bacterial entry. {ECO:0000269|PubMed:15133129, ECO:0000269|PubMed:17074883, ECO:0000269|PubMed:17875742}. |
| Q96E39 | RBMXL1 | S307 | ochoa | RNA binding motif protein, X-linked-like-1 (Heterogeneous nuclear ribonucleoprotein G-like 1) | RNA-binding protein which may be involved in pre-mRNA splicing. {ECO:0000250}. |
| Q96EV2 | RBM33 | S54 | ochoa | RNA-binding protein 33 (Proline-rich protein 8) (RNA-binding motif protein 33) | RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as mRNA export, mRNA stability and/or translation (PubMed:35589130, PubMed:37257451). Binds a subset of intronless RNAs containing GC-rich elements, such as NORAD, and promotes their nuclear export by recruiting target RNAs to components of the NXF1-NXT1 RNA export machinery (PubMed:35589130). Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, promoting their demethylation by ALKBH5 (PubMed:37257451). Acts as an molecular adapter, which (1) promotes ALKBH5 recruitment to m6A-containing transcripts and (2) activates ALKBH5 demethylase activity by recruiting SENP1, leading to ALKBH5 deSUMOylation and subsequent activation (PubMed:37257451). {ECO:0000269|PubMed:35589130, ECO:0000269|PubMed:37257451}. |
| Q96F46 | IL17RA | S629 | ochoa|psp | Interleukin-17 receptor A (IL-17 receptor A) (IL-17RA) (CDw217) (CD antigen CD217) | Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911633, PubMed:9367539). Receptor for IL17F (PubMed:17911633, PubMed:19838198). Binds to IL17A with higher affinity than to IL17F (PubMed:17911633). Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (PubMed:16785495). Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (PubMed:18684971). Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16785495, PubMed:17911633, PubMed:18684971, PubMed:21350122, PubMed:24120361). Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (By similarity). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity). Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (By similarity). Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848). {ECO:0000250|UniProtKB:Q60943, ECO:0000269|PubMed:16785495, ECO:0000269|PubMed:17911633, ECO:0000269|PubMed:18684971, ECO:0000269|PubMed:19838198, ECO:0000269|PubMed:21350122, ECO:0000269|PubMed:21993848, ECO:0000269|PubMed:24120361, ECO:0000269|PubMed:9367539}.; FUNCTION: (Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway. {ECO:0000269|PubMed:33723527}. |
| Q96G03 | PGM2 | S165 | ochoa | Phosphopentomutase (EC 5.4.2.7) (Glucose phosphomutase 2) (Phosphodeoxyribomutase) (Phosphoglucomutase-2) (EC 5.4.2.2) | Catalyzes the conversion of the nucleoside breakdown products ribose-1-phosphate and deoxyribose-1-phosphate to the corresponding 5-phosphopentoses (PubMed:17804405). Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate but with a lower catalytic efficiency (PubMed:17804405). The mechanism proceeds via the intermediate compound alpha-D-glucose 1,6-bisphosphate (PubMed:17804405). In vitro, also has a low glucose 1,6-bisphosphate synthase activity which is most probably not physiologically relevant (PubMed:17804405, PubMed:18927083). {ECO:0000269|PubMed:17804405, ECO:0000269|PubMed:18927083}. |
| Q96GA3 | LTV1 | S408 | ochoa | Protein LTV1 homolog | Essential for ribosome biogenesis. {ECO:0000250|UniProtKB:Q5U3J8}. |
| Q96GS4 | BORCS6 | S93 | ochoa | BLOC-1-related complex subunit 6 (Lysosome-dispersing protein) (Lyspersin) | As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor. {ECO:0000269|PubMed:25898167}. |
| Q96GX5 | MASTL | S657 | ochoa | Serine/threonine-protein kinase greatwall (GW) (GWL) (hGWL) (EC 2.7.11.1) (Microtubule-associated serine/threonine-protein kinase-like) (MAST-L) | Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance (PubMed:19680222). Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively (PubMed:38123684). ARPP19 and ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high (PubMed:20818157). Following DNA damage, it is also involved in checkpoint recovery by being inhibited. Phosphorylates histone protein in vitro; however such activity is unsure in vivo. May be involved in megakaryocyte differentiation. {ECO:0000269|PubMed:12890928, ECO:0000269|PubMed:19680222, ECO:0000269|PubMed:19793917, ECO:0000269|PubMed:20538976, ECO:0000269|PubMed:20818157, ECO:0000269|PubMed:38123684}. |
| Q96GX9 | APIP | S61 | ochoa | Methylthioribulose-1-phosphate dehydratase (MTRu-1-P dehydratase) (EC 4.2.1.109) (APAF1-interacting protein) (hAPIP) | Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death. {ECO:0000255|HAMAP-Rule:MF_03116, ECO:0000269|PubMed:15262985, ECO:0000269|PubMed:22837397, ECO:0000269|PubMed:23285211, ECO:0000269|PubMed:24367089}. |
| Q96H22 | CENPN | S282 | ochoa | Centromere protein N (CENP-N) (Interphase centromere complex protein 32) | Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate. {ECO:0000269|PubMed:16622419, ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:18007590, ECO:0000269|PubMed:19543270}. |
| Q96HB5 | CCDC120 | S331 | ochoa | Coiled-coil domain-containing protein 120 | Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells (PubMed:28422092). Together with CCDC68, cooperate with subdistal appendage components ODF2, NIN and CEP170 for hierarchical subdistal appendage assembly (PubMed:28422092). Recruits NIN and CEP170 to centrosomes (PubMed:28422092). Also required for neurite growth. Localizes CYTH2 to vesicles to allow its transport along neurites, and subsequent ARF6 activation and neurite growth. {ECO:0000269|PubMed:25326380}. |
| Q96HH9 | GRAMD2B | S212 | ochoa | GRAM domain-containing protein 2B (HCV NS3-transactivated protein 2) | None |
| Q96HS1 | PGAM5 | S113 | ochoa | Serine/threonine-protein phosphatase PGAM5, mitochondrial (EC 3.1.3.16) (Bcl-XL-binding protein v68) (Phosphoglycerate mutase family member 5) | Mitochondrial serine/threonine phosphatase that dephosphorylates various substrates and thus plays a role in different biological processes including cellular senescence or mitophagy (PubMed:24746696, PubMed:32439975). Modulates cellular senescence by regulating mitochondrial dynamics. Mechanistically, participates in mitochondrial fission through dephosphorylating DNM1L/DRP1 (PubMed:32439975). Additionally, dephosphorylates MFN2 in a stress-sensitive manner and consequently protects it from ubiquitination and degradation to promote mitochondrial network formation (PubMed:37498743). Regulates mitophagy independent of PARKIN by interacting with and dephosphorylating FUNDC1, which interacts with LC3 (PubMed:24746696). Regulates anti-oxidative response by forming a tertiary complex with KEAP1 and NRF2 (PubMed:18387606). Regulates necroptosis by acting as a RIPK3 target and recruiting the RIPK1-RIPK3-MLKL necrosis 'attack' complex to mitochondria (PubMed:22265414). {ECO:0000269|PubMed:18387606, ECO:0000269|PubMed:19590015, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:24746696, ECO:0000269|PubMed:32439975, ECO:0000269|PubMed:37498743}. |
| Q96I25 | RBM17 | S62 | ochoa|psp | Splicing factor 45 (45 kDa-splicing factor) (RNA-binding motif protein 17) | Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia. {ECO:0000269|PubMed:12015979, ECO:0000269|PubMed:17589525}. |
| Q96IF1 | AJUBA | S69 | ochoa | LIM domain-containing protein ajuba | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. {ECO:0000269|PubMed:12417594, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:15870274, ECO:0000269|PubMed:16413547, ECO:0000269|PubMed:17909014, ECO:0000269|PubMed:18805794, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:22286099}. |
| Q96J02 | ITCH | S221 | ochoa | E3 ubiquitin-protein ligase Itchy homolog (Itch) (EC 2.3.2.26) (Atrophin-1-interacting protein 4) (AIP4) (HECT-type E3 ubiquitin transferase Itchy homolog) (NFE2-associated polypeptide 1) (NAPP1) | Acts as an Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11046148, PubMed:14602072, PubMed:15051726, PubMed:16387660, PubMed:17028573, PubMed:18718448, PubMed:18718449, PubMed:19116316, PubMed:19592251, PubMed:19881509, PubMed:20068034, PubMed:20392206, PubMed:20491914, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885, PubMed:34927784). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Together with UBR5, involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP: catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP (PubMed:20068034, PubMed:29378950). ITCH synthesizes 'Lys-63'-linked chains, while UBR5 is branching multiple 'Lys-48'-linked chains of substrate initially modified (PubMed:29378950). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013). Ubiquitinates NEDD9/HEF1, resulting in proteasomal degradation of NEDD9/HEF1 (PubMed:15051726). {ECO:0000250|UniProtKB:Q8C863, ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:15051726, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316, ECO:0000269|PubMed:19131965, ECO:0000269|PubMed:19592251, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034, ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914, ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:30328013}. |
| Q96JM3 | CHAMP1 | S139 | ochoa | Chromosome alignment-maintaining phosphoprotein 1 (Zinc finger protein 828) | Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore. {ECO:0000269|PubMed:21063390}. |
| Q96JZ2 | HSH2D | S251 | ochoa | Hematopoietic SH2 domain-containing protein (Hematopoietic SH2 protein) (Adaptor in lymphocytes of unknown function X) | May be a modulator of the apoptotic response through its ability to affect mitochondrial stability (By similarity). Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated activation of the RE/AP element of the interleukin-2 promoter. {ECO:0000250, ECO:0000269|PubMed:11700021, ECO:0000269|PubMed:12960172, ECO:0000269|PubMed:15284240}. |
| Q96K17 | BTF3L4 | S109 | ochoa | Transcription factor BTF3 homolog 4 (Basic transcription factor 3-like 4) | None |
| Q96K21 | ZFYVE19 | S290 | ochoa | Abscission/NoCut checkpoint regulator (ANCHR) (MLL partner containing FYVE domain) (Zinc finger FYVE domain-containing protein 19) | Key regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. Together with CHMP4C, required to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ZFYVE19/ANCHR and VPS4 and subsequent abscission. {ECO:0000269|PubMed:24814515}. |
| Q96K76 | USP47 | S865 | ochoa | Ubiquitin carboxyl-terminal hydrolase 47 (EC 3.4.19.12) (Deubiquitinating enzyme 47) (Ubiquitin thioesterase 47) (Ubiquitin-specific-processing protease 47) | Ubiquitin-specific protease that specifically deubiquitinates monoubiquitinated DNA polymerase beta (POLB), stabilizing POLB thereby playing a role in base-excision repair (BER). Acts as a regulator of cell growth and genome integrity. May also indirectly regulate CDC25A expression at a transcriptional level. {ECO:0000269|PubMed:19966869, ECO:0000269|PubMed:21362556}. |
| Q96L91 | EP400 | S196 | ochoa | E1A-binding protein p400 (EC 3.6.4.-) (CAG repeat protein 32) (Domino homolog) (hDomino) (Trinucleotide repeat-containing gene 12 protein) (p400 kDa SWI2/SNF2-related protein) | Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. May be required for transcriptional activation of E2F1 and MYC target genes during cellular proliferation. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. May regulate ZNF42 transcription activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. {ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:24463511}. |
| Q96M11 | HYLS1 | S179 | ochoa | Centriolar and ciliogenesis-associated protein HYLS1 (Hydrolethalus syndrome protein 1) | Plays a role in ciliogenesis. {ECO:0000250|UniProtKB:A0A1L8ER70, ECO:0000250|UniProtKB:Q95X94}. |
| Q96M96 | FGD4 | S702 | ochoa | FYVE, RhoGEF and PH domain-containing protein 4 (Actin filament-binding protein frabin) (FGD1-related F-actin-binding protein) (Zinc finger FYVE domain-containing protein 6) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Activates MAPK8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:15133042}. |
| Q96ME7 | ZNF512 | S94 | ochoa | Zinc finger protein 512 | May be involved in transcriptional regulation. |
| Q96MG2 | JSRP1 | S46 | ochoa | Junctional sarcoplasmic reticulum protein 1 (Junctional-face membrane protein of 45 kDa homolog) (JP-45) | Involved in skeletal muscle excitation/contraction coupling (EC), probably acting as a regulator of the voltage-sensitive calcium channel CACNA1S. EC is a physiological process whereby an electrical signal (depolarization of the plasma membrane) is converted into a chemical signal, a calcium gradient, by the opening of ryanodine receptor calcium release channels. May regulate CACNA1S membrane targeting and activity. {ECO:0000269|PubMed:22927026}. |
| Q96MH2 | HEXIM2 | S169 | ochoa | Protein HEXIM2 (Hexamethylene bis-acetamide-inducible protein 2) | Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:15713661, PubMed:15713662). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:15713661, PubMed:15713662). {ECO:0000269|PubMed:15713661, ECO:0000269|PubMed:15713662}. |
| Q96MK2 | RIPOR3 | S603 | ochoa | RIPOR family member 3 | None |
| Q96MT8 | CEP63 | S437 | ochoa | Centrosomal protein of 63 kDa (Cep63) | Required for normal spindle assembly (PubMed:21406398, PubMed:21983783, PubMed:26297806, PubMed:35793002). Plays a key role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:21983783, PubMed:26297806). Reported to be required for centrosomal recruitment of CEP152; however, this function has been questioned (PubMed:21983783, PubMed:26297806). Also recruits CDK1 to centrosomes (PubMed:21406398). Plays a role in DNA damage response (PubMed:21406398). Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression (PubMed:21406398). Promotes stabilization of FXR1 protein by inhibiting FXR1 ubiquitination (PubMed:35989368). {ECO:0000269|PubMed:21406398, ECO:0000269|PubMed:21983783, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:35793002, ECO:0000269|PubMed:35989368}. |
| Q96MU7 | YTHDC1 | S588 | ochoa | YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) | Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. |
| Q96MY1 | NOL4L | S137 | ochoa | Nucleolar protein 4-like | None |
| Q96N21 | TEPSIN | S330 | ochoa | AP-4 complex accessory subunit Tepsin (ENTH domain-containing protein 2) (Epsin for AP-4) (Tetra-epsin) | Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network. {ECO:0000305|PubMed:22472443, ECO:0000305|PubMed:26542808}. |
| Q96N67 | DOCK7 | S873 | ochoa | Dedicator of cytokinesis protein 7 | Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}. |
| Q96NL1 | TMEM74 | S277 | ochoa | Transmembrane protein 74 | Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction. {ECO:0000269|PubMed:18294959, ECO:0000269|PubMed:19029833}. |
| Q96NU1 | SAMD11 | S418 | ochoa | Sterile alpha motif domain-containing protein 11 (SAM domain-containing protein 11) | Component of a Polycomb group (PcG) multiprotein PRC1-like complex, essential for establishing rod photoreceptor cell identity and function by silencing nonrod gene expression in developing rod photoreceptor cells. {ECO:0000250|UniProtKB:Q1RNF8}. |
| Q96P48 | ARAP1 | S1428 | ochoa | Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (Centaurin-delta-2) (Cnt-d2) | Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members (PubMed:11804590, PubMed:19666464). Activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding and, to a lesser extent, by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) binding (PubMed:11804590). Has a preference for ARF1 and ARF5 (PubMed:11804590, PubMed:19666464). Positively regulates the ring size of circular dorsal ruffles and promotes macropinocytosis (PubMed:22573888). Acts as a bridging factor in osteoclasts to control actin and membrane dynamics (By similarity). Regulates the condensing of osteoclast podosomes into sealing zones which segregate the bone-facing membrane from other membrane domains and are required for osteoclast resorption activity (By similarity). Also regulates recruitment of the AP-3 complex to endosomal membranes and trafficking of lysosomal membrane proteins to the ruffled membrane border of osteoclasts to modulate bone resorption (By similarity). Regulates the endocytic trafficking of EGFR (PubMed:18764928, PubMed:18939958, PubMed:21275903). Regulates the incorporation of CD63 and CD9 into multivesicular bodies (PubMed:38682696). Required in the retinal pigment epithelium (RPE) for photoreceptor survival due to its role in promoting RPE phagocytosis (By similarity). {ECO:0000250|UniProtKB:Q4LDD4, ECO:0000269|PubMed:11804590, ECO:0000269|PubMed:18764928, ECO:0000269|PubMed:18939958, ECO:0000269|PubMed:19666464, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:22573888, ECO:0000269|PubMed:38682696}. |
| Q96PE2 | ARHGEF17 | S410 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PE2 | ARHGEF17 | S717 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PE2 | ARHGEF17 | S790 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PE2 | ARHGEF17 | S946 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PM5 | RCHY1 | S211 | psp | RING finger and CHY zinc finger domain-containing protein 1 (EC 2.3.2.27) (Androgen receptor N-terminal-interacting protein) (CH-rich-interacting match with PLAG1) (E3 ubiquitin-protein ligase Pirh2) (RING finger protein 199) (RING-type E3 ubiquitin transferase RCHY1) (Zinc finger protein 363) (p53-induced RING-H2 protein) (hPirh2) | E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins, including p53/TP53, TP73, HDAC1 and CDKN1B (PubMed:16914734, PubMed:17721809, PubMed:18006823, PubMed:19043414, PubMed:19483087, PubMed:21994467). Mediates ubiquitination and degradation of p53/TP53; preferentially acts on tetrameric p53/TP53 (PubMed:19043414, PubMed:19483087). Catalyzes monoubiquitinates the translesion DNA polymerase POLH (PubMed:21791603). Involved in the ribosome-associated quality control (RQC) pathway, which mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes: RCHY1 acts downstream of NEMF and recognizes CAT tails associated with stalled nascent chains, leading to their ubiquitination and degradation (PubMed:33909987). {ECO:0000269|PubMed:16914734, ECO:0000269|PubMed:17721809, ECO:0000269|PubMed:18006823, ECO:0000269|PubMed:19043414, ECO:0000269|PubMed:19483087, ECO:0000269|PubMed:21791603, ECO:0000269|PubMed:21994467, ECO:0000269|PubMed:33909987}.; FUNCTION: [Isoform 4]: Has no E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20452352}. |
| Q96PU5 | NEDD4L | S428 | psp | E3 ubiquitin-protein ligase NEDD4-like (EC 2.3.2.26) (EC 2.3.2.36) (HECT-type E3 ubiquitin transferase NED4L) (NEDD4.2) (Nedd4-2) | E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:20064473, PubMed:31959741, PubMed:33608556). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556). Ubiquitinates TTYH2 and TTYH3 and regulates protein levels of TTYH2 (PubMed:18577513). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:18577513, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961, ECO:0000269|PubMed:33608556}. |
| Q96QC0 | PPP1R10 | S542 | ochoa | Serine/threonine-protein phosphatase 1 regulatory subunit 10 (MHC class I region proline-rich protein CAT53) (PP1-binding protein of 114 kDa) (Phosphatase 1 nuclear targeting subunit) (p99) | Substrate-recognition component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation (PubMed:39603239, PubMed:39603240). Promoter-proximal pausing by RNA polymerase II is a transcription halt following transcription initiation but prior to elongation, which acts as a checkpoint to control that transcripts are favorably configured for transcriptional elongation (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex also regulates RNA polymerase II transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription (PubMed:31677974). PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at 'Ser-5' of the CTD, promoting RNA polymerase II degradation (PubMed:33264625). The PNUTS-PP1 complex also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (By similarity). PNUTS-PP1 complex mediates dephosphorylation of MYC, promoting MYC stability by preventing MYC ubiquitination by the SCF(FBXW7) complex (PubMed:30158517). In addition to acts as a substrate-recognition component, PPP1R10/PNUTS also acts as a nuclear targeting subunit for the PNUTS-PP1 complex (PubMed:9450550). In some context, PPP1R10/PNUTS also acts as an inhibitor of protein phosphatase 1 (PP1) activity by preventing access to substrates, such as RB (PubMed:18360108). {ECO:0000250|UniProtKB:Q80W00, ECO:0000269|PubMed:18360108, ECO:0000269|PubMed:30158517, ECO:0000269|PubMed:31677974, ECO:0000269|PubMed:33264625, ECO:0000269|PubMed:39603239, ECO:0000269|PubMed:39603240, ECO:0000269|PubMed:9450550}. |
| Q96QT4 | TRPM7 | S101 | ochoa | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96QT4 | TRPM7 | S1598 | psp | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96QT4 | TRPM7 | S1695 | psp | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96QT4 | TRPM7 | S1779 | psp | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96QT6 | PHF12 | S772 | ochoa | PHD finger protein 12 (PHD factor 1) (Pf1) | Transcriptional repressor acting as key scaffolding subunit of SIN3 complexes which contributes to complex assembly by contacting each core subunit domain, stabilizes the complex and constitutes the substrate receptor by recruiting the H3 histone tail (PubMed:37137925). SIN3 complexes are composed of a SIN3 scaffold subunit, one catalytic core (HDAC1 or HDAC2) and 2 chromatin targeting modules (PubMed:11390640, PubMed:37137925). SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription (PubMed:21041482). May also repress transcription in a SIN3A-independent manner through recruitment of functional TLE5 complexes to DNA (PubMed:11390640). May also play a role in ribosomal biogenesis (By similarity). {ECO:0000250|UniProtKB:Q5SPL2, ECO:0000269|PubMed:11390640, ECO:0000269|PubMed:21041482, ECO:0000269|PubMed:37137925}. |
| Q96RG2 | PASK | S65 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RG2 | PASK | S584 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RG2 | PASK | S953 | ochoa|psp | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RI0 | F2RL3 | S366 | ochoa | Proteinase-activated receptor 4 (PAR-4) (Coagulation factor II receptor-like 3) (Thrombin receptor-like 3) | Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis (PubMed:10079109). May play a role in platelets activation (PubMed:10079109). {ECO:0000269|PubMed:10079109}. |
| Q96RL1 | UIMC1 | S168 | ochoa | BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) | Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}. |
| Q96RL1 | UIMC1 | S597 | ochoa | BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) | Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}. |
| Q96RT1 | ERBIN | S1020 | ochoa | Erbin (Densin-180-like protein) (Erbb2-interacting protein) (Protein LAP2) | Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and pro-inflammatory cytokine secretion (PubMed:16203728). {ECO:0000269|PubMed:10878805, ECO:0000269|PubMed:16203728}. |
| Q96RV3 | PCNX1 | S159 | ochoa | Pecanex-like protein 1 (Pecanex homolog protein 1) | None |
| Q96RV3 | PCNX1 | S198 | ochoa | Pecanex-like protein 1 (Pecanex homolog protein 1) | None |
| Q96S21 | RAB40C | S252 | ochoa | Ras-related protein Rab-40C (EC 3.6.5.2) (Rar-like protein) (Ras-like protein family member 8C) (SOCS box-containing protein RAR3) | RAB40C small GTPase acts as substrate-recognition component of the ECS(RAB40C) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820, PubMed:35512830). The Rab40 subfamily belongs to the Rab family that are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:29156729). As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration (PubMed:35512830). Also negatively regulate lipid droplets accumulation in a GTP-dependent manner (PubMed:29156729). {ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:29156729, ECO:0000269|PubMed:35512830}. |
| Q96S90 | LYSMD1 | S26 | ochoa | LysM and putative peptidoglycan-binding domain-containing protein 1 | None |
| Q96S94 | CCNL2 | S327 | ochoa | Cyclin-L2 (Paneth cell-enhanced expression protein) | Involved in pre-mRNA splicing. May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors. {ECO:0000269|PubMed:14684736, ECO:0000269|PubMed:18216018}. |
| Q96S94 | CCNL2 | S441 | ochoa | Cyclin-L2 (Paneth cell-enhanced expression protein) | Involved in pre-mRNA splicing. May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors. {ECO:0000269|PubMed:14684736, ECO:0000269|PubMed:18216018}. |
| Q96SN8 | CDK5RAP2 | S366 | ochoa | CDK5 regulatory subunit-associated protein 2 (CDK5 activator-binding protein C48) (Centrosome-associated protein 215) | Potential regulator of CDK5 activity via its interaction with CDK5R1 (PubMed:15164053). Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter (PubMed:19282672). Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends (PubMed:18042621, PubMed:17959831, PubMed:19553473). Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gTuRC) onto centrosomes (PubMed:18042621, PubMed:17959831, PubMed:26485573, PubMed:39321809). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q8K389, ECO:0000269|PubMed:15164053, ECO:0000269|PubMed:17959831, ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697, ECO:0000269|PubMed:39321809}. |
| Q96T23 | RSF1 | S700 | ochoa | Remodeling and spacing factor 1 (Rsf-1) (HBV pX-associated protein 8) (Hepatitis B virus X-associated protein) (p325 subunit of RSF chromatin-remodeling complex) | Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF-alpha induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984). {ECO:0000269|PubMed:11788598, ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:28801535}. |
| Q96T58 | SPEN | S1076 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96T58 | SPEN | S2789 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96T88 | UHRF1 | S709 | ochoa | E3 ubiquitin-protein ligase UHRF1 (EC 2.3.2.27) (Inverted CCAAT box-binding protein of 90 kDa) (Nuclear protein 95) (Nuclear zinc finger protein Np95) (HuNp95) (hNp95) (RING finger protein 106) (RING-type E3 ubiquitin transferase UHRF1) (Transcription factor ICBP90) (Ubiquitin-like PHD and RING finger domain-containing protein 1) (hUHRF1) (Ubiquitin-like-containing PHD and RING finger domains protein 1) | Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF2 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation. Acts as a critical player of proper spindle architecture by catalyzing the 'Lys-63'-linked ubiquitination of KIF11, thereby controlling KIF11 localization on the spindle (PubMed:37728657). {ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:22945642, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:37728657}. |
| Q99426 | TBCB | S65 | psp | Tubulin-folding cofactor B (Cytoskeleton-associated protein 1) (Cytoskeleton-associated protein CKAPI) (Tubulin-specific chaperone B) | Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer (PubMed:9265649). Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth (By similarity). {ECO:0000250|UniProtKB:Q9D1E6, ECO:0000269|PubMed:9265649}. |
| Q99459 | CDC5L | S390 | ochoa | Cell division cycle 5-like protein (Cdc5-like protein) (Pombe cdc5-related protein) | DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30705154, PubMed:30728453). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:11082045, ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9468527, ECO:0000269|PubMed:9632794, ECO:0000305|PubMed:33509932}. |
| Q99569 | PKP4 | S162 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99569 | PKP4 | S438 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99570 | PIK3R4 | S865 | ochoa | Phosphoinositide 3-kinase regulatory subunit 4 (PI3-kinase regulatory subunit 4) (EC 2.7.11.1) (PI3-kinase p150 subunit) (Phosphoinositide 3-kinase adaptor protein) | Regulatory subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123). {ECO:0000269|PubMed:20643123}. |
| Q99575 | POP1 | S584 | ochoa | Ribonucleases P/MRP protein subunit POP1 (hPOP1) | Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:30454648, PubMed:8918471). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465). {ECO:0000269|PubMed:28115465, ECO:0000269|PubMed:30454648, ECO:0000269|PubMed:8918471}. |
| Q99576 | TSC22D3 | S111 | ochoa | TSC22 domain family protein 3 (DSIP-immunoreactive peptide) (Protein DIP) (hDIP) (Delta sleep-inducing peptide immunoreactor) (Glucocorticoid-induced leucine zipper protein) (GILZ) (TSC-22-like protein) (TSC-22-related protein) (TSC-22R) | Protects T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3A transcriptional activity that leads to the down-regulation of the pro-apoptotic factor BCL2L11 (PubMed:15031210). In macrophages, plays a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10 (PubMed:12393603). In T-cells, inhibits anti-CD3-induced NFKB1 nuclear translocation and thereby NFKB1 DNA-binding activities (PubMed:11468175). In vitro, suppresses AP-1 transcription factor complex DNA-binding activities (By similarity). {ECO:0000250|UniProtKB:Q9Z2S7, ECO:0000269|PubMed:11468175, ECO:0000269|PubMed:12393603, ECO:0000269|PubMed:15031210}.; FUNCTION: [Isoform 1]: Inhibits myogenic differentiation and mediates anti-myogenic effects of glucocorticoids by binding and regulating MYOD1 and HDAC1 transcriptional activity resulting in reduced expression of MYOG. {ECO:0000250|UniProtKB:Q9Z2S7}. |
| Q99626 | CDX2 | S176 | ochoa | Homeobox protein CDX-2 (CDX-3) (Caudal-type homeobox protein 2) | Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium (By similarity). Binds to the promoter of the intestinal sucrase-isomaltase SI and activates SI transcription (By similarity). Binds to the DNA sequence 5'-ATAAAAACTTAT-3' in the promoter region of VDR and activates VDR transcription (By similarity). Binds to and activates transcription of LPH (By similarity). Activates transcription of CLDN2 and intestinal mucin MUC2 (By similarity). Binds to the 5'-AATTTTTTACAACACCT-3' DNA sequence in the promoter region of CA1 and activates CA1 transcription (By similarity). Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000250|UniProtKB:P43241, ECO:0000250|UniProtKB:Q04649, ECO:0000269|PubMed:28473536}. |
| Q99638 | RAD9A | S266 | ochoa | Cell cycle checkpoint control protein RAD9A (hRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A) | Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10713044, PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:21659603). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). RAD9A possesses 3'->5' double stranded DNA exonuclease activity (PubMed:10713044). {ECO:0000269|PubMed:10713044, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:31135337}. |
| Q99640 | PKMYT1 | S120 | ochoa | Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (EC 2.7.11.1) (Myt1 kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins (PubMed:10373560, PubMed:10504341, PubMed:9001210, PubMed:9268380). Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation (PubMed:9001210, PubMed:9268380). May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect (PubMed:9001210, PubMed:9268380). {ECO:0000269|PubMed:10373560, ECO:0000269|PubMed:10504341, ECO:0000269|PubMed:9001210, ECO:0000269|PubMed:9268380}. |
| Q99640 | PKMYT1 | S479 | ochoa | Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (EC 2.7.11.1) (Myt1 kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins (PubMed:10373560, PubMed:10504341, PubMed:9001210, PubMed:9268380). Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation (PubMed:9001210, PubMed:9268380). May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect (PubMed:9001210, PubMed:9268380). {ECO:0000269|PubMed:10373560, ECO:0000269|PubMed:10504341, ECO:0000269|PubMed:9001210, ECO:0000269|PubMed:9268380}. |
| Q99661 | KIF2C | S22 | ochoa | Kinesin-like protein KIF2C (Kinesin-like protein 6) (Mitotic centromere-associated kinesin) (MCAK) | In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells (PubMed:21820309). Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis (PubMed:19060894). Plays a role in chromosome congression and is required for the lateral to end-on conversion of the chromosome-microtubule attachment (PubMed:23891108). {ECO:0000269|PubMed:19060894, ECO:0000269|PubMed:21820309, ECO:0000269|PubMed:23891108}. |
| Q99698 | LYST | S2124 | ochoa | Lysosomal-trafficking regulator (Beige homolog) | Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (PubMed:11984006, PubMed:25216107). Might regulate trafficking of effectors involved in exocytosis (PubMed:25425525). In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules (PubMed:26478006). In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes (By similarity). In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways (PubMed:27881733). {ECO:0000250|UniProtKB:P97412, ECO:0000269|PubMed:11984006, ECO:0000269|PubMed:25216107, ECO:0000269|PubMed:25425525, ECO:0000269|PubMed:26478006, ECO:0000269|PubMed:27881733}. |
| Q99700 | ATXN2 | S521 | ochoa | Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) | Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}. |
| Q99750 | MDFI | S141 | ochoa | MyoD family inhibitor (Myogenic repressor I-mf) | Inhibits the transactivation activity of the Myod family of myogenic factors and represses myogenesis (By similarity). Acts by associating with Myod family members and retaining them in the cytoplasm by masking their nuclear localization signals (By similarity). Can also interfere with the DNA-binding activity of Myod family members (By similarity). Plays an important role in trophoblast and chondrogenic differentiation (By similarity). Regulates the transcriptional activity of TCF7L1/TCF3 by interacting directly with TCF7L1/TCF3 and preventing it from binding DNA (By similarity). Binds to the axin complex, resulting in an increase in the level of free beta-catenin (By similarity). Affects axin regulation of the WNT and JNK signaling pathways (By similarity). Regulates the activity of mechanosensitive Piezo channel (PubMed:37590348). {ECO:0000250}. |
| Q99816 | TSG101 | S48 | ochoa | Tumor susceptibility gene 101 protein (ESCRT-I complex subunit TSG101) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426). {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:21070952, ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:22660413}. |
| Q99816 | TSG101 | S309 | ochoa | Tumor susceptibility gene 101 protein (ESCRT-I complex subunit TSG101) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426). {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:21070952, ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:22660413}. |
| Q99832 | CCT7 | S59 | psp | T-complex protein 1 subunit eta (TCP-1-eta) (EC 3.6.1.-) (CCT-eta) (Chaperonin containing T-complex polypeptide 1 subunit 7) (HIV-1 Nef-interacting protein) [Cleaved into: T-complex protein 1 subunit eta, N-terminally processed] | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q99877 | H2BC15 | S57 | ochoa | Histone H2B type 1-N (Histone H2B.d) (H2B/d) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q99879 | H2BC14 | S57 | ochoa | Histone H2B type 1-M (Histone H2B.e) (H2B/e) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q99880 | H2BC13 | S57 | ochoa | Histone H2B type 1-L (Histone H2B.c) (H2B/c) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q99959 | PKP2 | S329 | ochoa | Plakophilin-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297). {ECO:0000250|UniProtKB:F1M7L9, ECO:0000250|UniProtKB:Q9CQ73, ECO:0000269|PubMed:18662195, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:22781308, ECO:0000269|PubMed:23884246, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:28169297, ECO:0000269|PubMed:34368962, ECO:0000269|PubMed:35959657}. |
| Q9BQ24 | ZFYVE21 | S32 | ochoa | Zinc finger FYVE domain-containing protein 21 (ZF21) | Plays a role in cell adhesion, and thereby in cell motility which requires repeated formation and disassembly of focal adhesions. Regulates microtubule-induced PTK2/FAK1 dephosphorylation, an event important for focal adhesion disassembly, as well as integrin beta-1/ITGB1 cell surface expression. {ECO:0000269|PubMed:20439989, ECO:0000269|PubMed:21768110}. |
| Q9BQG0 | MYBBP1A | S1203 | ochoa | Myb-binding protein 1A | May activate or repress transcription via interactions with sequence specific DNA-binding proteins (By similarity). Repression may be mediated at least in part by histone deacetylase activity (HDAC activity) (By similarity). Acts as a corepressor and in concert with CRY1, represses the transcription of the core circadian clock component PER2 (By similarity). Preferentially binds to dimethylated histone H3 'Lys-9' (H3K9me2) on the PER2 promoter (By similarity). Has a role in rRNA biogenesis together with PWP1 (PubMed:29065309). {ECO:0000250|UniProtKB:Q7TPV4, ECO:0000269|PubMed:29065309}. |
| Q9BQI9 | NRIP2 | S96 | ochoa | Nuclear receptor-interacting protein 2 | Down-regulates transcriptional activation by nuclear receptors such as NR1F2. {ECO:0000250}. |
| Q9BQP7 | MGME1 | S71 | ochoa | Mitochondrial genome maintenance exonuclease 1 (EC 3.1.-.-) | Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endonuclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells. {ECO:0000255|HAMAP-Rule:MF_03030, ECO:0000269|PubMed:23313956, ECO:0000269|PubMed:23358826}. |
| Q9BQQ3 | GORASP1 | S189 | psp | Golgi reassembly-stacking protein 1 (Golgi peripheral membrane protein p65) (Golgi phosphoprotein 5) (GOLPH5) (Golgi reassembly-stacking protein of 65 kDa) (GRASP65) | Key structural protein of the Golgi apparatus (PubMed:33301566). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon (PubMed:33301566). Acting in concert with GORASP2/GRASP55, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks (PubMed:33301566). However, other studies suggest that GORASP1 plays an important role in assembly and membrane stacking of the cisternae, and in the reassembly of Golgi stacks after breakdown during mitosis (By similarity). Caspase-mediated cleavage of GORASP1 is required for fragmentation of the Golgi during apoptosis (By similarity). Also mediates, via its interaction with GOLGA2/GM130, the docking of transport vesicles with the Golgi membranes (PubMed:16489344). Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (PubMed:21884936). {ECO:0000250|UniProtKB:O35254, ECO:0000269|PubMed:16489344, ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:33301566}. |
| Q9BR76 | CORO1B | S423 | ochoa | Coronin-1B (Coronin-2) | Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity). {ECO:0000250, ECO:0000269|PubMed:16027158}. |
| Q9BRD0 | BUD13 | S28 | ochoa | BUD13 homolog | Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}. |
| Q9BRK4 | LZTS2 | S570 | ochoa | Leucine zipper putative tumor suppressor 2 (hLZTS2) (Protein LAPSER1) | Negative regulator of katanin-mediated microtubule severing and release from the centrosome. Required for central spindle formation and the completion of cytokinesis. May negatively regulate axonal outgrowth by preventing the formation of microtubule bundles that are necessary for transport within the elongating axon. Negative regulator of the Wnt signaling pathway. Represses beta-catenin-mediated transcriptional activation by promoting the nuclear exclusion of beta-catenin. {ECO:0000255|HAMAP-Rule:MF_03026, ECO:0000269|PubMed:17000760, ECO:0000269|PubMed:17351128, ECO:0000269|PubMed:17950943, ECO:0000269|PubMed:18490357}. |
| Q9BRR8 | GPATCH1 | S357 | ochoa | G patch domain-containing protein 1 (Evolutionarily conserved G-patch domain-containing protein) | None |
| Q9BRR9 | ARHGAP9 | S113 | ochoa | Rho GTPase-activating protein 9 (Rho-type GTPase-activating protein 9) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has a substantial GAP activity toward CDC42 and RAC1 and less toward RHOA. Has a role in regulating adhesion of hematopoietic cells to the extracellular matrix. Binds phosphoinositides, and has the highest affinity for phosphatidylinositol 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:11396949}. |
| Q9BRY0 | SLC39A3 | S125 | ochoa | Zinc transporter ZIP3 (Solute carrier family 39 member 3) (Zrt- and Irt-like protein 3) (ZIP-3) | Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space. Controls Zn(2+) accumulation into dentate gyrus granule cells in the hippocampus. Mediates Zn(2+) reuptake from the secreted milk within the alveolar lumen. {ECO:0000250|UniProtKB:Q99K24}. |
| Q9BSW2 | CRACR2A | S26 | ochoa | EF-hand calcium-binding domain-containing protein 4B (Calcium release-activated calcium channel regulator 2A) (CRAC channel regulator 2A) (Calcium release-activated channel regulator 2A) (Ras-related protein Rab-46) (EC 3.6.5.2) | [Isoform 1]: Ca(2+)-binding protein that plays a key role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation. Acts as a cytoplasmic calcium-sensor that facilitates the clustering of ORAI1 and STIM1 at the junctional regions between the plasma membrane and the endoplasmic reticulum upon low Ca(2+) concentration. It thereby regulates CRAC channel activation, including translocation and clustering of ORAI1 and STIM1. Upon increase of cytoplasmic Ca(2+) resulting from opening of CRAC channels, dissociates from ORAI1 and STIM1, thereby destabilizing the ORAI1-STIM1 complex. {ECO:0000269|PubMed:20418871, ECO:0000269|PubMed:27016526}.; FUNCTION: [Isoform 2]: Rab GTPase that mediates the trafficking of Weibel-Palade bodies (WPBs) to microtubule organizing center (MTOC) in endothelial cells in response to acute inflammatory stimuli (PubMed:31092558). During histamine (but not thrombin) stimulation of endothelial cells, the dynein-bound form induces retrograde transport of a subset of WPBs along microtubules to the MTOC in a Ca(2+)-independent manner and its GTPase activity is essential for this function (PubMed:31092558). Ca(2+)-regulated dynein adapter protein that activates dynein-mediated transport and dynein-dynactin motility on microtubules and regulates endosomal trafficking of CD47 (PubMed:30814157). Acts as an intracellular signaling module bridging two important T-cell receptor (TCR) signaling pathways, Ca(2+)-NFAT and JNK, to affect T-cell activation (PubMed:27016526). In resting T-cells, is predominantly localized near TGN network in a GTP-bound form, upon TCR stimulation, localizes at the immunological synapse via interaction with VAV1 to activate downstream Ca(2+)-NFAT and JNK signaling pathways (PubMed:27016526). Plays a role in T-helper 1 (Th1) cell differentiation and T-helper 17 (Th17) cell effector function (PubMed:29987160). Plays a role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation (PubMed:27016526). {ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:29987160, ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}. |
| Q9BTC0 | DIDO1 | S203 | ochoa | Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) | Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}. |
| Q9BU70 | TRMO | S214 | ochoa | tRNA (adenine(37)-N6)-methyltransferase (EC 2.1.1.-) (tRNA methyltransferase O) | S-adenosyl-L-methionine-dependent methyltransferase responsible for the addition of the methyl group in the formation of N6-methyl-N6-threonylcarbamoyladenosine at position 37 (m(6)t(6)A37) of the tRNA anticodon loop of tRNA(Ser)(GCU) (PubMed:25063302). The methyl group of m(6)t(6)A37 may improve the efficiency of the tRNA decoding ability (By similarity). {ECO:0000250|UniProtKB:P28634, ECO:0000269|PubMed:25063302}. |
| Q9BUJ2 | HNRNPUL1 | S512 | ochoa | Heterogeneous nuclear ribonucleoprotein U-like protein 1 (Adenovirus early region 1B-associated protein 5) (E1B-55 kDa-associated protein 5) (E1B-AP5) | Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Also plays a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro. {ECO:0000269|PubMed:12489984, ECO:0000269|PubMed:9733834}. |
| Q9BUR4 | WRAP53 | S125 | ochoa | Telomerase Cajal body protein 1 (WD repeat-containing protein 79) (WD40 repeat-containing protein antisense to TP53 gene) (WRAP53beta) | RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies (PubMed:29695869, PubMed:29804836). Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC) (PubMed:19285445, PubMed:20351177, PubMed:29695869, PubMed:29804836). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes (PubMed:19179534, PubMed:20351177, PubMed:26170453, PubMed:29695869). In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex (PubMed:27525486, PubMed:29804836). Acts by specifically binding the CAB box of the TERC RNA and controlling the folding of the CR4/CR5 region of the TERC RNA, a critical step for telomerase activity (PubMed:29804836). In addition, also controls telomerase holoenzyme complex localization to Cajal body (PubMed:22547674). During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity (PubMed:29804836). In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies (PubMed:19285445, PubMed:21072240). Also plays a role in DNA repair: phosphorylated by ATM in response to DNA damage and relocalizes to sites of DNA double-strand breaks to promote the repair of DNA double-strand breaks (PubMed:25512560, PubMed:27715493). Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non-homologous end joining (NHEJ) (PubMed:25512560, PubMed:27715493). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:19285445, ECO:0000269|PubMed:20351177, ECO:0000269|PubMed:21072240, ECO:0000269|PubMed:22547674, ECO:0000269|PubMed:25512560, ECO:0000269|PubMed:26170453, ECO:0000269|PubMed:27525486, ECO:0000269|PubMed:27715493, ECO:0000269|PubMed:29695869, ECO:0000269|PubMed:29804836}. |
| Q9BV38 | WDR18 | S368 | ochoa | WD repeat-containing protein 18 | Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211). May play a role during development (By similarity). {ECO:0000250|UniProtKB:Q68EI0, ECO:0000269|PubMed:21326211, ECO:0000269|PubMed:22872859}. |
| Q9BV40 | VAMP8 | S55 | ochoa|psp | Vesicle-associated membrane protein 8 (VAMP-8) (Endobrevin) (EDB) | SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (PubMed:23217709, PubMed:25686604). Also required for dense-granule secretion in platelets (PubMed:12130530). Also plays a role in regulated enzyme secretion in pancreatic acinar cells (By similarity). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Also participates in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (PubMed:31694946). {ECO:0000250|UniProtKB:Q9WUF4, ECO:0000269|PubMed:12130530, ECO:0000269|PubMed:23217709, ECO:0000269|PubMed:25686604, ECO:0000269|PubMed:31694946}. |
| Q9BVC5 | C2orf49 | S112 | ochoa | Ashwin | None |
| Q9BVG8 | KIFC3 | S781 | ochoa | Kinesin-like protein KIFC3 | Minus-end microtubule-dependent motor protein. Involved in apically targeted transport (By similarity). Required for zonula adherens maintenance. {ECO:0000250, ECO:0000269|PubMed:19041755}. |
| Q9BVT8 | TMUB1 | S127 | ochoa | Transmembrane and ubiquitin-like domain-containing protein 1 (Dendritic cell-derived ubiquitin-like protein) (DULP) (Hepatocyte odd protein shuttling protein) (Ubiquitin-like protein SB144) [Cleaved into: iHOPS] | Involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR (PubMed:21343306). Involved in positive regulation of AMPA-selective glutamate receptor GRIA2 recycling to the cell surface (By similarity). Acts as a negative regulator of hepatocyte growth during regeneration (By similarity). {ECO:0000250|UniProtKB:Q53AQ4, ECO:0000250|UniProtKB:Q9JMG3, ECO:0000269|PubMed:21343306}.; FUNCTION: [iHOPS]: May contribute to the regulation of translation during cell-cycle progression. May contribute to the regulation of cell proliferation (By similarity). May be involved in centrosome assembly. Modulates stabilization and nucleolar localization of tumor suppressor CDKN2A and enhances association between CDKN2A and NPM1 (By similarity). {ECO:0000250|UniProtKB:Q9JMG3}. |
| Q9BW04 | SARG | S513 | ochoa | Specifically androgen-regulated gene protein | Putative androgen-specific receptor. {ECO:0000269|PubMed:15525603}. |
| Q9BWC9 | CCDC106 | S147 | psp | Coiled-coil domain-containing protein 106 | Promotes the degradation of p53/TP53 protein and inhibits its transactivity. {ECO:0000269|PubMed:20159018}. |
| Q9BWQ6 | YIPF2 | S46 | ochoa | Protein YIPF2 (YIP1 family member 2) | None |
| Q9BX40 | LSM14B | S165 | ochoa | Protein LSM14 homolog B (RNA-associated protein 55B) (hRAP55B) | mRNA-binding protein essential for female fertility, oocyte meiotic maturation and the assembly of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes. Ensures the proper accumulation and clearance of mRNAs essential for oocyte meiotic maturation and the normal progression from Meiosis I to Meiosis II in oocytes. Promotes the translation of some oogenesis-related mRNAs. Regulates the expression and/or localization of some key P-body proteins in oocytes. Essential for the assembly of the primordial follicle in the ovary. {ECO:0000250|UniProtKB:Q8CGC4}. |
| Q9BXB4 | OSBPL11 | S286 | ochoa | Oxysterol-binding protein-related protein 11 (ORP-11) (OSBP-related protein 11) | Plays a role in regulating ADIPOQ and FABP4 levels in differentiating adipocytes and is also involved in regulation of adipocyte triglyceride storage (PubMed:23028956). Weakly binds 25-hydroxycholesterol (PubMed:17428193). Interacts with OSBPL9 to function as lipid transfer proteins (PubMed:39106189). Together they form a heterodimer that localizes at the ER-trans-Golgi membrane contact sites, and exchanges phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) for phosphatidylinositol-4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), PI(4)P) between the two organelles, a step that is critical for sphingomyelin synthesis in the Golgi complex (PubMed:39106189). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:23028956, ECO:0000269|PubMed:39106189}. |
| Q9BXB5 | OSBPL10 | S322 | ochoa | Oxysterol-binding protein-related protein 10 (ORP-10) (OSBP-related protein 10) | Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable) (PubMed:23934110). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:19554302, ECO:0000269|PubMed:22906437, ECO:0000269|PubMed:23934110, ECO:0000305}. |
| Q9BXF6 | RAB11FIP5 | S224 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BXF6 | RAB11FIP5 | S332 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BXS6 | NUSAP1 | S269 | ochoa | Nucleolar and spindle-associated protein 1 (NuSAP) | Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules around them. {ECO:0000250, ECO:0000269|PubMed:12963707}. |
| Q9BXT4 | TDRD1 | S678 | ochoa | Tudor domain-containing protein 1 (Cancer/testis antigen 41.1) (CT41.1) | Plays a central role during spermatogenesis by participating in the repression transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins (By similarity). {ECO:0000250}. |
| Q9BY89 | KIAA1671 | S518 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYB0 | SHANK3 | S555 | ochoa | SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) | Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. {ECO:0000269|PubMed:24132240}. |
| Q9BYB0 | SHANK3 | S980 | ochoa | SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) | Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. {ECO:0000269|PubMed:24132240}. |
| Q9BYB0 | SHANK3 | S1031 | ochoa | SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) | Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. {ECO:0000269|PubMed:24132240}. |
| Q9BYW2 | SETD2 | S1144 | ochoa | Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) | Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. |
| Q9BZ29 | DOCK9 | S40 | ochoa | Dedicator of cytokinesis protein 9 (Cdc42 guanine nucleotide exchange factor zizimin-1) (Zizimin-1) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation. {ECO:0000269|PubMed:12172552, ECO:0000269|PubMed:19745154}. |
| Q9BZ29 | DOCK9 | S440 | ochoa | Dedicator of cytokinesis protein 9 (Cdc42 guanine nucleotide exchange factor zizimin-1) (Zizimin-1) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation. {ECO:0000269|PubMed:12172552, ECO:0000269|PubMed:19745154}. |
| Q9BZE9 | ASPSCR1 | S165 | ochoa | Tether containing UBX domain for GLUT4 (Alveolar soft part sarcoma chromosomal region candidate gene 1 protein) (Alveolar soft part sarcoma locus) (Renal papillary cell carcinoma protein 17) (UBX domain-containing protein 9) | Tethering protein that sequesters GLUT4-containing vesicles in the cytoplasm in the absence of insulin. Modulates the amount of GLUT4 that is available at the cell surface (By similarity). Enhances VCP methylation catalyzed by VCPKMT. {ECO:0000250, ECO:0000269|PubMed:23349634}. |
| Q9BZF2 | OSBPL7 | S272 | ochoa | Oxysterol-binding protein-related protein 7 (ORP-7) (OSBP-related protein 7) | None |
| Q9BZI7 | UPF3B | S25 | ochoa | Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B) (Up-frameshift suppressor 3 homolog B) (hUpf3B) (Up-frameshift suppressor 3 homolog on chromosome X) (hUpf3p-X) | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}. |
| Q9BZL4 | PPP1R12C | S427 | ochoa | Protein phosphatase 1 regulatory subunit 12C (Protein phosphatase 1 myosin-binding subunit of 85 kDa) (Protein phosphatase 1 myosin-binding subunit p85) | Regulates myosin phosphatase activity. {ECO:0000269|PubMed:11399775}. |
| Q9C026 | TRIM9 | S76 | psp | E3 ubiquitin-protein ligase TRIM9 (EC 2.3.2.27) (RING finger protein 91) (RING-type E3 ubiquitin transferase TRIM9) (Tripartite motif-containing protein 9) | E3 ubiquitin-protein ligase which ubiquitinates itself in cooperation with an E2 enzyme UBE2D2/UBC4 and serves as a targeting signal for proteasomal degradation. May play a role in regulation of neuronal functions and may also participate in the formation or breakdown of abnormal inclusions in neurodegenerative disorders. May act as a regulator of synaptic vesicle exocytosis by controlling the availability of SNAP25 for the SNARE complex formation. {ECO:0000269|PubMed:20085810}. |
| Q9C026 | TRIM9 | S80 | psp | E3 ubiquitin-protein ligase TRIM9 (EC 2.3.2.27) (RING finger protein 91) (RING-type E3 ubiquitin transferase TRIM9) (Tripartite motif-containing protein 9) | E3 ubiquitin-protein ligase which ubiquitinates itself in cooperation with an E2 enzyme UBE2D2/UBC4 and serves as a targeting signal for proteasomal degradation. May play a role in regulation of neuronal functions and may also participate in the formation or breakdown of abnormal inclusions in neurodegenerative disorders. May act as a regulator of synaptic vesicle exocytosis by controlling the availability of SNAP25 for the SNARE complex formation. {ECO:0000269|PubMed:20085810}. |
| Q9C040 | TRIM2 | S375 | ochoa | Tripartite motif-containing protein 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRIM2) (RING finger protein 86) (RING-type E3 ubiquitin transferase TRIM2) | UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance. Plays a role in antiviral immunity and limits New World arenavirus infection independently of its ubiquitin ligase activity (PubMed:24068738). {ECO:0000250|UniProtKB:Q9ESN6, ECO:0000269|PubMed:24068738}. |
| Q9C073 | FAM117A | S178 | ochoa | Protein FAM117A (C/EBP-induced protein) | None |
| Q9C0B0 | UNK | S546 | psp | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9C0B0 | UNK | S565 | psp | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9C0B5 | ZDHHC5 | S577 | ochoa | Palmitoyltransferase ZDHHC5 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 5) (DHHC-5) (Zinc finger protein 375) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sensing or cardiac functions (PubMed:21820437, PubMed:29185452, PubMed:31402609, PubMed:31649195, PubMed:34293401, PubMed:38092000, PubMed:38530158, PubMed:38599239). Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:26334723). Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins (PubMed:26334723). Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2 (PubMed:26334723). Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2 (PubMed:31402609). Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes (PubMed:31649195, PubMed:34293401). Also participates in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:32958780). Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis (PubMed:32958780). Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (By similarity). Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD (PubMed:38092000, PubMed:38530158, PubMed:38599239). Palmitoylates NLRP3 to promote inflammasome assembly and activation (PubMed:38092000). Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158, PubMed:38599239). {ECO:0000250|UniProtKB:Q8VDZ4, ECO:0000269|PubMed:21820437, ECO:0000269|PubMed:26334723, ECO:0000269|PubMed:29185452, ECO:0000269|PubMed:31402609, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:32958780, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:38092000, ECO:0000269|PubMed:38530158, ECO:0000269|PubMed:38599239}. |
| Q9C0C2 | TNKS1BP1 | S214 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S446 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S456 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1013 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1158 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1178 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1181 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1328 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1331 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C6 | CIPC | S239 | ochoa | CLOCK-interacting pacemaker (CLOCK-interacting circadian protein) | Transcriptional repressor which may act as a negative-feedback regulator of CLOCK-BMAL1 transcriptional activity in the circadian-clock mechanism. May stimulate BMAL1-dependent phosphorylation of CLOCK. However, the physiological relevance of these observations is unsure, since experiments in an animal model showed that CIPC is not critially required for basic circadian clock. {ECO:0000250|UniProtKB:Q8R0W1}. |
| Q9C0K0 | BCL11B | S483 | ochoa | B-cell lymphoma/leukemia 11B (BCL-11B) (B-cell CLL/lymphoma 11B) (COUP-TF-interacting protein 2) (Radiation-induced tumor suppressor gene 1 protein) (hRit1) | Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC-rich response element (By similarity). May also function in the P53-signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q99PV8, ECO:0000269|PubMed:16809611, ECO:0000269|PubMed:27959755}. |
| Q9GZR2 | REXO4 | S226 | ochoa | RNA exonuclease 4 (EC 3.1.-.-) (Exonuclease XPMC2) (Prevents mitotic catastrophe 2 protein homolog) (hPMC2) | None |
| Q9GZR2 | REXO4 | S383 | ochoa | RNA exonuclease 4 (EC 3.1.-.-) (Exonuclease XPMC2) (Prevents mitotic catastrophe 2 protein homolog) (hPMC2) | None |
| Q9GZY6 | LAT2 | S55 | ochoa | Linker for activation of T-cells family member 2 (Linker for activation of B-cells) (Membrane-associated adapter molecule) (Non-T-cell activation linker) (Williams-Beuren syndrome chromosomal region 15 protein) (Williams-Beuren syndrome chromosomal region 5 protein) | Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2. {ECO:0000269|PubMed:12486104, ECO:0000269|PubMed:12514734, ECO:0000269|PubMed:15010370}. |
| Q9GZY6 | LAT2 | S102 | ochoa | Linker for activation of T-cells family member 2 (Linker for activation of B-cells) (Membrane-associated adapter molecule) (Non-T-cell activation linker) (Williams-Beuren syndrome chromosomal region 15 protein) (Williams-Beuren syndrome chromosomal region 5 protein) | Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2. {ECO:0000269|PubMed:12486104, ECO:0000269|PubMed:12514734, ECO:0000269|PubMed:15010370}. |
| Q9H0H0 | INTS2 | S356 | ochoa | Integrator complex subunit 2 (Int2) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:33243860, PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:33243860, PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:38570683}. |
| Q9H1A4 | ANAPC1 | S547 | ochoa | Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9H1A4 | ANAPC1 | S686 | ochoa | Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9H1A4 | ANAPC1 | S703 | ochoa | Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9H1Z4 | WDR13 | S74 | ochoa | WD repeat-containing protein 13 | None |
| Q9H257 | CARD9 | S460 | ochoa | Caspase recruitment domain-containing protein 9 (hCARD9) | Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (PubMed:26961233, PubMed:33558980). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (PubMed:24231284, PubMed:25057046, PubMed:25702837, PubMed:26521038, PubMed:26679537, PubMed:26961233, PubMed:27777981, PubMed:29080677, PubMed:33558980). Transduces signals in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated molecular pattern metabolites (PAMPs), such as fungal carbohydrates, and trigger CARD9 activation (By similarity). Upon activation, CARD9 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:11053425, PubMed:26488816, PubMed:26961233, PubMed:31296852, PubMed:33558980). CARD9 signaling in antigen-presenting cells links innate sensing of fungi to the activation of adaptive immunity and provides a cytokine milieu that induces the development and subsequent of interleukin 17-producing T helper (Th17) cells (PubMed:24231284). Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). CARD9 can also be engaged independently of BCL10: forms a complex with RASGRF1 downstream of C-type lectin receptors, which recruits and activates HRAS, leading to ERK activation and the production of cytokines (By similarity). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (PubMed:33548172). Plays an essential role in antifungal immunity against dissemination of gut fungi: acts by promoting induction of antifungal IgG antibodies response in CX3CR1(+) macrophages to confer protection against disseminated C.albicans or C.auris infection (PubMed:33548172). Also mediates immunity against other pathogens, such as certain bacteria, viruses and parasites; CARD9 signaling is however redundant with other innate immune responses (By similarity). In response to L.monocytogenes infection, required for the production of inflammatory cytokines activated by intracellular peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B (By similarity). {ECO:0000250|UniProtKB:A2AIV8, ECO:0000269|PubMed:11053425, ECO:0000269|PubMed:24231284, ECO:0000269|PubMed:25057046, ECO:0000269|PubMed:25702837, ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:26521038, ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:26961233, ECO:0000269|PubMed:27777981, ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:33548172, ECO:0000269|PubMed:33558980}. |
| Q9H2E6 | SEMA6A | S265 | ochoa | Semaphorin-6A (Semaphorin VIA) (Sema VIA) (Semaphorin-6A-1) (SEMA6A-1) | Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation. {ECO:0000250|UniProtKB:O35464}.; FUNCTION: (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium. {ECO:0000269|PubMed:32302524, ECO:0000269|PubMed:32589945}. |
| Q9H2S9 | IKZF4 | S142 | ochoa | Zinc finger protein Eos (Ikaros family zinc finger protein 4) | DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-binding sequence. Transcriptional repressor. Interacts with SPI1 and MITF to repress transcription of the CTSK and ACP5 promoters via recruitment of corepressors SIN3A and CTBP2. May be involved in the development of central and peripheral nervous systems. Essential for the inhibitory function of regulatory T-cells (Treg). Mediates FOXP3-mediated gene silencing in regulatory T-cells (Treg) via recruitment of corepressor CTBP1 (By similarity). {ECO:0000250|UniProtKB:Q8C208, ECO:0000269|PubMed:10978333, ECO:0000269|PubMed:12015313, ECO:0000269|PubMed:12444977}. |
| Q9H2V7 | SPNS1 | S505 | ochoa | Protein spinster homolog 1 (HSpin1) (SPNS1) (Spinster-like protein 1) | Plays a critical role in the phospholipid salvage pathway from lysosomes to the cytosol (PubMed:36161949, PubMed:37075117). Mediates the rate-limiting, proton-dependent, lysosomal efflux of lysophospholipids, which can then be reacylated by acyltransferases in the endoplasmic reticulum to form phospholipids (PubMed:36161949, PubMed:37075117). Selective for zwitterionic headgroups such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), can also transport lysophosphatidylglycerol (LPG), but not other anionic lysophospholipids, sphingosine, nor sphingomyelin (PubMed:36161949). Transports lysophospholipids with saturated, monounsaturated, and polyunsaturated fatty acids, such as 1-hexadecanoyl-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine and 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, respectively (PubMed:36161949, PubMed:37075117). Can also transport lysoplasmalogen (LPC with a fatty alcohol) such as 1-(1Z-hexadecenyl)-sn-glycero-3-phosphocholine (PubMed:36161949). Lysosomal LPC could function as intracellular signaling messenger (PubMed:37075117). Essential player in lysosomal homeostasis (PubMed:36161949). Crucial for cell survival under conditions of nutrient limitation (PubMed:37075117). May be involved in necrotic or autophagic cell death (PubMed:12815463). {ECO:0000269|PubMed:12815463, ECO:0000269|PubMed:36161949, ECO:0000269|PubMed:37075117, ECO:0000303|PubMed:37075117}. |
| Q9H3P7 | ACBD3 | S315 | ochoa | Golgi resident protein GCP60 (Acyl-CoA-binding domain-containing protein 3) (Golgi complex-associated protein 1) (GOCAP1) (Golgi phosphoprotein 1) (GOLPH1) (PBR- and PKA-associated protein 7) (Peripheral benzodiazepine receptor-associated protein PAP7) [Cleaved into: Golgi resident protein GCP60, N-terminally processed] | Involved in the maintenance of Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and Golgi (PubMed:11590181). Involved in hormone-induced steroid biosynthesis in testicular Leydig cells (By similarity). Recruits PI4KB to the Golgi apparatus membrane; enhances the enzyme activity of PI4KB activity via its membrane recruitment thereby increasing the local concentration of the substrate in the vicinity of the kinase (PubMed:27009356). {ECO:0000250|UniProtKB:Q8BMP6, ECO:0000269|PubMed:11590181, ECO:0000269|PubMed:27009356}.; FUNCTION: (Microbial infection) Plays an essential role in Aichi virus RNA replication by recruiting PI4KB at the viral replication sites. {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:22258260, ECO:0000269|PubMed:27989622}. |
| Q9H3Q1 | CDC42EP4 | S105 | ochoa | Cdc42 effector protein 4 (Binder of Rho GTPases 4) | Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation, when overexpressed in fibroblasts. |
| Q9H3R2 | MUC13 | S482 | ochoa | Mucin-13 (MUC-13) (Down-regulated in colon cancer 1) | Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling. |
| Q9H400 | LIME1 | S74 | ochoa | Lck-interacting transmembrane adapter 1 (Lck-interacting membrane protein) (Lck-interacting molecule) | Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. In absence of TCR signaling, may be involved in CD4-mediated inhibition of T-cell activation. Couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilization or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules. {ECO:0000269|PubMed:14610046}. |
| Q9H4A3 | WNK1 | S1220 | ochoa | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9H4G0 | EPB41L1 | S667 | ochoa | Band 4.1-like protein 1 (Erythrocyte membrane protein band 4.1-like 1) (Neuronal protein 4.1) (4.1N) | May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases. |
| Q9H4G0 | EPB41L1 | S672 | ochoa | Band 4.1-like protein 1 (Erythrocyte membrane protein band 4.1-like 1) (Neuronal protein 4.1) (4.1N) | May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases. |
| Q9H4I2 | ZHX3 | S899 | ochoa | Zinc fingers and homeoboxes protein 3 (Triple homeobox protein 1) (Zinc finger and homeodomain protein 3) | Acts as a transcriptional repressor. Involved in the early stages of mesenchymal stem cell (MSC) osteogenic differentiation. Is a regulator of podocyte gene expression during primary glomerula disease. Binds to promoter DNA. {ECO:0000269|PubMed:12659632, ECO:0000269|PubMed:21174497}. |
| Q9H4L5 | OSBPL3 | S197 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H582 | ZNF644 | S619 | ochoa | Zinc finger protein 644 (Zinc finger motif enhancer-binding protein 2) (Zep-2) | May be involved in transcriptional regulation. |
| Q9H5I5 | PIEZO2 | S838 | ochoa | Piezo-type mechanosensitive ion channel component 2 (Protein FAM38B) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). {ECO:0000250|UniProtKB:Q8CD54, ECO:0000269|PubMed:33057202, ECO:0000269|PubMed:37590348}. |
| Q9H6A9 | PCNX3 | S171 | ochoa | Pecanex-like protein 3 (Pecanex homolog protein 3) | None |
| Q9H6V9 | LDAH | S98 | ochoa | Lipid droplet-associated hydrolase (EC 3.1.1.13) (Lipid droplet-associated serine hydrolase) (hLDAH) | Probable serine lipid hydrolase associated with lipid droplets (By similarity). Has low cholesterol esterase activity (By similarity). Appears to lack triglyceride lipase activity (By similarity). Involved in cholesterol and triglyceride homeostasis; has opposing effects, stimulating cellular triglyceride accumulation and cellular cholesterol release (PubMed:24357060, PubMed:28578400). Acts antagonistically with PNPLA2/ATGL in regulation of cellular lipid stores (PubMed:28578400). May regulate triglyceride accumulation indirectly through stimulation of PNPLA2/ATGL ubiquitination and proteasomal degradation (PubMed:28578400). Promotes microtubule-dependent lipid droplet fusion (PubMed:28578400). Highly expressed in macrophage-rich areas in atherosclerotic lesions, suggesting that it could promote cholesterol ester turnover in macrophages (By similarity). {ECO:0000250|UniProtKB:Q8BVA5, ECO:0000269|PubMed:24357060, ECO:0000269|PubMed:28578400}. |
| Q9H792 | PEAK1 | S914 | ochoa | Inactive tyrosine-protein kinase PEAK1 (Pseudopodium-enriched atypical kinase 1) (Sugen kinase 269) (Tyrosine-protein kinase SgK269) | Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics (PubMed:20534451, PubMed:23105102, PubMed:35687021). Acts as a scaffold for mediating EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654, ECO:0000269|PubMed:35687021}. |
| Q9H8Y5 | ANKZF1 | S533 | ochoa | tRNA endonuclease ANKZF1 (EC 3.1.-.-) (Ankyrin repeat and zinc finger domain-containing protein 1) (Zinc finger protein 744) | Endonuclease that cleaves polypeptidyl-tRNAs downstream of the ribosome-associated quality control (RQC) pathway to release incompletely synthesized polypeptides for degradation (PubMed:29632312, PubMed:30244831, PubMed:31011209). The RQC pathway disassembles aberrantly stalled translation complexes to recycle or degrade the constituent parts (PubMed:29632312, PubMed:30244831, PubMed:31011209). ANKZF1 acts downstream disassembly of stalled ribosomes and specifically cleaves off the terminal 3'-CCA nucleotides universal to all tRNAs from polypeptidyl-tRNAs, releasing (1) ubiquitinated polypeptides from 60S ribosomal subunit for degradation and (2) cleaved tRNAs (PubMed:31011209). ANKZF1-cleaved tRNAs are then repaired and recycled by ELAC1 and TRNT1 (PubMed:31011209, PubMed:32075755). Also plays a role in the cellular response to hydrogen peroxide and in the maintenance of mitochondrial integrity under conditions of cellular stress (PubMed:28302725). {ECO:0000269|PubMed:28302725, ECO:0000269|PubMed:29632312, ECO:0000269|PubMed:30244831, ECO:0000269|PubMed:31011209, ECO:0000269|PubMed:32075755}. |
| Q9H8Y8 | GORASP2 | S189 | psp | Golgi reassembly-stacking protein 2 (GRS2) (Golgi phosphoprotein 6) (GOLPH6) (Golgi reassembly-stacking protein of 55 kDa) (GRASP55) (p59) | Key structural protein of the Golgi apparatus (PubMed:33301566). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon (PubMed:33301566). Acting in concert with GORASP1/GRASP65, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks (PubMed:33301566). However, other studies suggest that GORASP2 plays a role in the assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after breakdown during mitosis and meiosis (PubMed:10487747, PubMed:21515684, PubMed:22523075). May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA (PubMed:11101516). Required for normal acrosome formation during spermiogenesis and normal male fertility, probably by promoting colocalization of JAM2 and JAM3 at contact sites between germ cells and Sertoli cells (By similarity). Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (PubMed:21884936, PubMed:27062250, PubMed:28067262). {ECO:0000250|UniProtKB:Q99JX3, ECO:0000269|PubMed:10487747, ECO:0000269|PubMed:11101516, ECO:0000269|PubMed:21515684, ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:22523075, ECO:0000269|PubMed:27062250, ECO:0000269|PubMed:28067262}. |
| Q9H910 | JPT2 | S69 | ochoa | Jupiter microtubule associated homolog 2 (Hematological and neurological expressed 1-like protein) (HN1-like protein) | Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein required for NAADP-evoked intracellular calcium release (PubMed:33758061, PubMed:33758062). Confers NAADP-sensitivity to the two pore channels (TPCs) complex (PubMed:33758061). Enables NAADP to activate Ca(2+) release from the endoplasmic reticulum through ryanodine receptors (PubMed:33758062). {ECO:0000269|PubMed:33758061, ECO:0000269|PubMed:33758062}.; FUNCTION: (Microbial infection) Involved in the endolysosomal trafficking of human coronavirus SARS-CoV-2. {ECO:0000269|PubMed:33758061}. |
| Q9H987 | SYNPO2L | S374 | ochoa | Synaptopodin 2-like protein | Actin-associated protein that may play a role in modulating actin-based shape. {ECO:0000250}. |
| Q9H9D4 | ZNF408 | S345 | ochoa | Zinc finger protein 408 (PR domain zinc finger protein 17) | May be involved in transcriptional regulation. |
| Q9H9G7 | AGO3 | S829 | ochoa | Protein argonaute-3 (Argonaute3) (hAgo3) (EC 3.1.26.n2) (Argonaute RISC catalytic component 3) (Eukaryotic translation initiation factor 2C 3) (eIF-2C 3) (eIF2C 3) | Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Proposed to be involved in stabilization of small RNA derivates (siRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent siRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4. Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity (PubMed:29040713). {ECO:0000255|HAMAP-Rule:MF_03032, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:23064648, ECO:0000269|PubMed:29040713}. |
| Q9HAF1 | MEAF6 | S118 | ochoa | Chromatin modification-related protein MEAF6 (MYST/Esa1-associated factor 6) (Esa1-associated factor 6 homolog) (Protein EAF6 homolog) (hEAF6) (Sarcoma antigen NY-SAR-91) | Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A (PubMed:14966270). This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4 (PubMed:16387653, PubMed:24065767). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (PubMed:18794358). {ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:24065767}. |
| Q9HAS0 | C17orf75 | S59 | ochoa | Protein Njmu-R1 | As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). May have a role in spermatogenesis. {ECO:0000269|PubMed:29426865}. |
| Q9HAU0 | PLEKHA5 | S357 | ochoa | Pleckstrin homology domain-containing family A member 5 (PH domain-containing family A member 5) (Phosphoinositol 3-phosphate-binding protein 2) (PEPP-2) | None |
| Q9HAU4 | SMURF2 | S44 | ochoa | E3 ubiquitin-protein ligase SMURF2 (hSMURF2) (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase SMURF2) (SMAD ubiquitination regulatory factor 2) (SMAD-specific E3 ubiquitin-protein ligase 2) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11016919). Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling (PubMed:11163210, PubMed:12717440, PubMed:21791611). In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069). Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation (PubMed:11016919, PubMed:11158580, PubMed:11389444). SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444). Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809). {ECO:0000269|PubMed:11016919, ECO:0000269|PubMed:11158580, ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440, ECO:0000269|PubMed:18448069, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:30696809}.; FUNCTION: (Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding. {ECO:0000269|PubMed:33673144}. |
| Q9HAV4 | XPO5 | S1137 | ochoa | Exportin-5 (Exp5) (Ran-binding protein 21) | Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and release of the cargo from the export receptor. XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi). Mediates nuclear export of isoform 5 of ADAR/ADAR1 in a RanGTP-dependent manner.; FUNCTION: Mediates the nuclear export of micro-RNA precursors, which form short hairpins (PubMed:14631048, PubMed:14681208, PubMed:15613540). Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference. In some circumstances can also mediate the nuclear export of deacylated and aminoacylated tRNAs. Specifically recognizes dsRNAs that lack a 5'-overhang in a sequence-independent manner, have only a short 3'-overhang, and that have a double-stranded length of at least 15 base-pairs (PubMed:19965479). Binding is dependent on Ran-GTP (PubMed:19965479). {ECO:0000269|PubMed:14631048, ECO:0000269|PubMed:14681208, ECO:0000269|PubMed:15613540, ECO:0000269|PubMed:19965479}.; FUNCTION: (Microbial infection) Mediates the nuclear export of adenovirus VA1 dsRNA. {ECO:0000269|PubMed:12509441}. |
| Q9HBE1 | PATZ1 | S585 | ochoa | POZ-, AT hook-, and zinc finger-containing protein 1 (BTB/POZ domain zinc finger transcription factor) (Protein kinase A RI subunit alpha-associated protein) (Zinc finger and BTB domain-containing protein 19) (Zinc finger protein 278) (Zinc finger sarcoma gene protein) | Transcriptional regulator that plays a role in many biological processes such as embryogenesis, senescence, T-cell development or neurogenesis (PubMed:10713105, PubMed:25755280, PubMed:31875552). Interacts with the TP53 protein to control genes that are important in proliferation and in the DNA-damage response. Mechanistically, the interaction inhibits the DNA binding and transcriptional activity of TP53/p53 (PubMed:25755280). Part of the transcriptional network modulating regulatory T-cell development and controls the generation of the regulatory T-cell pool under homeostatic conditions (PubMed:31875552). {ECO:0000269|PubMed:10713105, ECO:0000269|PubMed:25755280, ECO:0000269|PubMed:31875552}.; FUNCTION: (Microbial infection) Plays a positive role in viral cDNA synthesis. {ECO:0000269|PubMed:31060775}. |
| Q9HBE5 | IL21R | S299 | ochoa | Interleukin-21 receptor (IL-21 receptor) (IL-21R) (Novel interleukin receptor) (CD antigen CD360) | This is a receptor for interleukin-21. |
| Q9HC07 | TMEM165 | S221 | ochoa | Putative divalent cation/proton antiporter TMEM165 (Transmembrane protein 165) (Transmembrane protein PT27) (Transmembrane protein TPARL) | Putative divalent cation:proton antiporter that exchanges calcium or manganese ions for protons across the Golgi membrane. Mediates the reversible transport of calcium or manganese to the Golgi lumen driven by the proton gradient and possibly the membrane potential generated by V-ATPase. Provides calcium or manganese cofactors to resident Golgi enzymes and contributes to the maintenance of an acidic luminal Golgi pH required for proper functioning of the secretory pathway (By similarity) (PubMed:22683087, PubMed:23569283, PubMed:27008884, PubMed:32047108). Promotes Ca(2+) storage within the Golgi lumen of the mammary epithelial cells to be then secreted into milk (By similarity). The transport mechanism and stoichiometry remains to be elucidated. {ECO:0000250|UniProtKB:P38301, ECO:0000250|UniProtKB:P52875, ECO:0000269|PubMed:22683087, ECO:0000269|PubMed:23569283, ECO:0000269|PubMed:27008884, ECO:0000269|PubMed:32047108}. |
| Q9HC44 | GPBP1L1 | S70 | ochoa | Vasculin-like protein 1 (GC-rich promoter-binding protein 1-like 1) | Possible transcription factor. {ECO:0000305}. |
| Q9HCD6 | TANC2 | S1744 | ochoa | Protein TANC2 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2) | Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines. {ECO:0000269|PubMed:30021165}. |
| Q9HCE7 | SMURF1 | S148 | ochoa | E3 ubiquitin-protein ligase SMURF1 (hSMURF1) (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase SMURF1) (SMAD ubiquitination regulatory factor 1) (SMAD-specific E3 ubiquitin-protein ligase 1) | E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway. Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway. Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA. Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Acts as an antagonist of TGF-beta signaling by ubiquitinating TGFBR1 and targeting it for degradation (PubMed:21791611). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:10458166, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23999003}. |
| Q9HCJ3 | RAVER2 | S622 | ochoa | Ribonucleoprotein PTB-binding 2 (Protein raver-2) | May bind single-stranded nucleic acids. {ECO:0000305}. |
| Q9HCN3 | PGAP6 | S399 | ochoa | Post-GPI attachment to proteins factor 6 (EC 3.1.1.4) (GPI processing phospholipase A2) (GPI-PLA2) (Protein M83) (Transmembrane protein 6) (Transmembrane protein 8) (Transmembrane protein 8A) | Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchor proteins (GPI-AP). Has phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI. Required for the shedding of the GPI-AP CRIPTO, but not CFC1, at the cell surface. Shedding of CRIPTO modulates Nodal signaling by allowing soluble CRIPTO to act as a Nodal coreceptor on other cells (PubMed:27881714). Also indirectly involved in the translocation of RAC1 from the cytosol to the plasma membrane by maintaining the steady state amount of CAV1-enriched plasma membrane subdomains, stabilizing RAC1 at the plasma membrane (PubMed:27835684). In contrast to myomaker (TMEM8C), has no fusogenic activity (PubMed:26858401). {ECO:0000269|PubMed:26858401, ECO:0000269|PubMed:27835684, ECO:0000269|PubMed:27881714}. |
| Q9HD20 | ATP13A1 | S644 | ochoa | Endoplasmic reticulum transmembrane helix translocase (EC 7.4.2.-) (Endoplasmic reticulum P5A-ATPase) | Endoplasmic reticulum translocase required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum (PubMed:32973005, PubMed:36264797). Acts as a dislocase that mediates the ATP-dependent extraction of mislocalized mitochondrial transmembrane proteins from the endoplasmic reticulum membrane (PubMed:32973005). Specifically binds mitochondrial tail-anchored transmembrane proteins: has an atypically large substrate-binding pocket that recognizes and binds moderately hydrophobic transmembranes with short hydrophilic lumenal domains (PubMed:32973005). {ECO:0000269|PubMed:32973005, ECO:0000269|PubMed:36264797}. |
| Q9HD20 | ATP13A1 | S945 | ochoa | Endoplasmic reticulum transmembrane helix translocase (EC 7.4.2.-) (Endoplasmic reticulum P5A-ATPase) | Endoplasmic reticulum translocase required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum (PubMed:32973005, PubMed:36264797). Acts as a dislocase that mediates the ATP-dependent extraction of mislocalized mitochondrial transmembrane proteins from the endoplasmic reticulum membrane (PubMed:32973005). Specifically binds mitochondrial tail-anchored transmembrane proteins: has an atypically large substrate-binding pocket that recognizes and binds moderately hydrophobic transmembranes with short hydrophilic lumenal domains (PubMed:32973005). {ECO:0000269|PubMed:32973005, ECO:0000269|PubMed:36264797}. |
| Q9HD42 | CHMP1A | S179 | psp | Charged multivesicular body protein 1a (Chromatin-modifying protein 1a) (CHMP1a) (Vacuolar protein sorting-associated protein 46-1) (Vps46-1) (hVps46-1) | Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing. {ECO:0000269|PubMed:11559747, ECO:0000269|PubMed:11559748, ECO:0000269|PubMed:19129479, ECO:0000269|PubMed:23045692}. |
| Q9HD64 | XAGE1A | S20 | ochoa | X antigen family member 1 (XAGE-1) (Cancer/testis antigen 12.1) (CT12.1) (G antigen family D member 2) | None |
| Q9NP80 | PNPLA8 | S511 | psp | Calcium-independent phospholipase A2-gamma (EC 3.1.1.-) (EC 3.1.1.5) (Intracellular membrane-associated calcium-independent phospholipase A2 gamma) (iPLA2-gamma) (PNPLA-gamma) (Patatin-like phospholipase domain-containing protein 8) (iPLA2-2) | Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release of lipid second messengers and growth factors (PubMed:10744668, PubMed:10833412, PubMed:15695510, PubMed:15908428, PubMed:17213206, PubMed:18171998, PubMed:28442572). Hydrolyzes phosphatidylethanolamine, phosphatidylcholine and probably phosphatidylinositol with a possible preference for the former (PubMed:15695510). Also has a broad substrate specificity in terms of fatty acid moieties, hydrolyzing saturated and mono-unsaturated fatty acids at nearly equal rates from either the sn-1 or sn-2 position in diacyl phosphatidylcholine (PubMed:10744668, PubMed:10833412, PubMed:15695510, PubMed:15908428). However, has a weak activity toward polyunsaturated fatty acids at the sn-2 position, and thereby favors the production of 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling (PubMed:15908428). On the other hand, can produce arachidonic acid from the sn-1 position of diacyl phospholipid and from the sn-2 position of arachidonate-containing plasmalogen substrates (PubMed:15908428). Therefore, plays an important role in the mobilization of arachidonic acid in response to cellular stimuli and the generation of lipid second messengers (PubMed:15695510, PubMed:15908428). Can also hydrolyze lysophosphatidylcholine (PubMed:15695510). In the mitochondrial compartment, catalyzes the hydrolysis and release of oxidized aliphatic chains from cardiolipin and integrates mitochondrial bioenergetics and signaling. It is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition (PubMed:28442572). {ECO:0000250|UniProtKB:Q8K1N1, ECO:0000269|PubMed:10744668, ECO:0000269|PubMed:10833412, ECO:0000269|PubMed:15695510, ECO:0000269|PubMed:15908428, ECO:0000269|PubMed:17213206, ECO:0000269|PubMed:18171998, ECO:0000269|PubMed:28442572}. |
| Q9NPA3 | MID1IP1 | S79 | ochoa | Mid1-interacting protein 1 (Gastrulation-specific G12-like protein) (Mid1-interacting G12-like protein) (Protein STRAIT11499) (Spot 14-related protein) (S14R) (Spot 14-R) | Plays a role in the regulation of lipogenesis in liver. Up-regulates ACACA enzyme activity. Required for efficient lipid biosynthesis, including triacylglycerol, diacylglycerol and phospholipid. Involved in stabilization of microtubules (By similarity). {ECO:0000250}. |
| Q9NPD8 | UBE2T | S177 | ochoa | Ubiquitin-conjugating enzyme E2 T (EC 2.3.2.23) (Cell proliferation-inducing gene 50 protein) (E2 ubiquitin-conjugating enzyme T) (Ubiquitin carrier protein T) (Ubiquitin-protein ligase T) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair. Acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784, PubMed:28437106). Also mediates monoubiquitination of FANCL and FANCI (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784). May contribute to ubiquitination and degradation of BRCA1 (PubMed:19887602). In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:20061386). {ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:17938197, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784, ECO:0000269|PubMed:19887602, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:28437106}. |
| Q9NPG3 | UBN1 | S1004 | ochoa | Ubinuclein-1 (HIRA-binding protein) (Protein VT4) (Ubiquitously expressed nuclear protein) | Acts as a novel regulator of senescence. Involved in the formation of senescence-associated heterochromatin foci (SAHF), which represses expression of proliferation-promoting genes. Binds to proliferation-promoting genes. May be required for replication-independent chromatin assembly. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:19029251}. |
| Q9NPI6 | DCP1A | S194 | ochoa | mRNA-decapping enzyme 1A (EC 3.6.1.62) (Smad4-interacting transcriptional co-activator) (Transcription factor SMIF) | Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:12417715). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12417715). Contributes to the transactivation of target genes after stimulation by TGFB1 (PubMed:11836524). Essential for embryonic development (PubMed:33813271). {ECO:0000269|PubMed:11836524, ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:33813271}. |
| Q9NQ31 | AKIP1 | S150 | ochoa | A-kinase-interacting protein 1 (Breast cancer-associated gene 3 protein) (PKA-interacting protein) (Proline-rich protein BCA3) | Enhances NF-kappa-B transcriptional activity by regulating the nuclear localization of the NF-kappa-B subunit RELA and promoting the phosphorylation of RELA by PRKACA. Regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade. {ECO:0000269|PubMed:18178962, ECO:0000269|PubMed:20562110}. |
| Q9NQ66 | PLCB1 | S887 | psp | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (EC 3.1.4.11) (PLC-154) (Phosphoinositide phospholipase C-beta-1) (Phospholipase C-I) (PLC-I) (Phospholipase C-beta-1) (PLC-beta-1) | Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors (PubMed:9188725). Regulates the function of the endothelial barrier. {ECO:0000250|UniProtKB:Q9Z1B3, ECO:0000269|PubMed:9188725}. |
| Q9NQ84 | GPRC5C | S403 | ochoa | G-protein coupled receptor family C group 5 member C (Retinoic acid-induced gene 3 protein) (RAIG-3) | This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways. {ECO:0000250}. |
| Q9NQ86 | TRIM36 | S73 | ochoa | E3 ubiquitin-protein ligase TRIM36 (EC 2.3.2.27) (RING finger protein 98) (RING-type E3 ubiquitin transferase TRIM36) (Tripartite motif-containing protein 36) (Zinc-binding protein Rbcc728) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Involved in chromosome segregation and cell cycle regulation (PubMed:28087737). May play a role in the acrosome reaction and fertilization. {ECO:0000250|UniProtKB:Q80WG7, ECO:0000269|PubMed:28087737}. |
| Q9NQS3 | NECTIN3 | S469 | ochoa | Nectin-3 (CDw113) (Nectin cell adhesion molecule 3) (Poliovirus receptor-related protein 3) (CD antigen CD113) | Cell adhesion molecule that promotes cell-cell adhesion through heterophilic trans-interactions with nectins-like or other nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions (PubMed:16216929). Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1 (PubMed:16216929). Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation (PubMed:16216929). Involved in axon guidance by promoting contacts between the commissural axons and the floor plate cells (By similarity). Also involved in the formation of cell-cell junctions, including adherens junctions and synapses (By similarity). Promotes formation of checkerboard-like cellular pattern of hair cells and supporting cells in the auditory epithelium via heterophilic interaction with NECTIN1: NECTIN1 is present in the membrane of hair cells and associates with NECTIN3 on supporting cells, thereby mediating heterotypic adhesion between these two cell types (By similarity). Plays a role in the morphology of the ciliary body (By similarity). {ECO:0000250|UniProtKB:Q9JLB9, ECO:0000269|PubMed:16216929}. |
| Q9NQS7 | INCENP | S119 | ochoa | Inner centromere protein | Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules (PubMed:12925766, PubMed:15316025, PubMed:27332895). The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC (PubMed:27332895). Required for localization of CBX5 to mitotic centromeres (PubMed:21346195). Controls the kinetochore localization of BUB1 (PubMed:16760428). {ECO:0000250|UniProtKB:P53352, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:21346195, ECO:0000269|PubMed:27332895}. |
| Q9NQV6 | PRDM10 | S803 | ochoa | PR domain zinc finger protein 10 (PR domain-containing protein 10) (Tristanin) | Transcriptional activator, essential for early embryonic development and survival of embryonic stem cells (ESCs) (By similarity). Supports cell growth and survival during early development by transcriptionally activating the expression of the translation initiation factor EIF3B, to sustain global translation (By similarity). Activates the transcription of FLNC (PubMed:36440963). {ECO:0000250|UniProtKB:Q3UTQ7, ECO:0000269|PubMed:36440963}. |
| Q9NQW6 | ANLN | S141 | ochoa | Anillin | Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}. |
| Q9NQW6 | ANLN | S336 | ochoa | Anillin | Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}. |
| Q9NQW6 | ANLN | S485 | ochoa | Anillin | Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}. |
| Q9NR12 | PDLIM7 | S274 | ochoa | PDZ and LIM domain protein 7 (LIM mineralization protein) (LMP) (Protein enigma) | May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Involved in both of the two fundamental mechanisms of bone formation, direct bone formation (e.g. embryonic flat bones mandible and cranium), and endochondral bone formation (e.g. embryonic long bone development). Plays a role during fracture repair. Involved in BMP6 signaling pathway (By similarity). {ECO:0000250, ECO:0000269|PubMed:11874232, ECO:0000269|PubMed:7929196}. |
| Q9NR48 | ASH1L | S2951 | ochoa | Histone-lysine N-methyltransferase ASH1L (EC 2.1.1.359) (EC 2.1.1.367) (ASH1-like protein) (huASH1) (Absent small and homeotic disks protein 1 homolog) (Lysine N-methyltransferase 2H) | Histone methyltransferase specifically trimethylating 'Lys-36' of histone H3 forming H3K36me3 (PubMed:21239497). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). The physiological significance of the H3K9me1 activity is unclear (By similarity). {ECO:0000250|UniProtKB:Q99MY8, ECO:0000269|PubMed:21239497}. |
| Q9NR50 | EIF2B3 | S428 | ochoa | Translation initiation factor eIF2B subunit gamma (eIF2B GDP-GTP exchange factor subunit gamma) | Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on the eukaryotic initiation factor 2 (eIF2) complex gamma subunit (PubMed:25858979, PubMed:27023709, PubMed:31048492). Its guanine nucleotide exchange factor activity is repressed when bound to eIF2 complex phosphorylated on the alpha subunit, thereby limiting the amount of methionyl-initiator methionine tRNA available to the ribosome and consequently global translation is repressed (PubMed:25858979, PubMed:31048492). {ECO:0000269|PubMed:25858979, ECO:0000269|PubMed:27023709, ECO:0000269|PubMed:31048492}. |
| Q9NR81 | ARHGEF3 | S399 | ochoa | Rho guanine nucleotide exchange factor 3 (Exchange factor found in platelets and leukemic and neuronal tissues) (XPLN) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases. {ECO:0000269|PubMed:12221096}. |
| Q9NR82 | KCNQ5 | S669 | ochoa | Potassium voltage-gated channel subfamily KQT member 5 (KQT-like 5) (Potassium channel subunit alpha KvLQT5) (Voltage-gated potassium channel subunit Kv7.5) | Pore-forming subunit of the voltage-gated potassium (Kv) channel broadly expressed in brain and involved in the regulation of neuronal excitability (PubMed:10787416, PubMed:10816588, PubMed:11159685, PubMed:28669405). Associates with KCNQ3/Kv7.3 pore-forming subunit to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons (PubMed:10816588, PubMed:11159685). Contributes, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current (PubMed:10816588). Also forms a functional channel with KCNQ1/Kv7.1 subunit that may contribute to vasoconstriction and hypertension (PubMed:24855057). Channel may be selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) = Rb(+) > Cs(+) > Na(+) (PubMed:10816588). Similar to the native M-channel, KCNQ3-KCNQ5 potassium channel is suppressed by activation of the muscarinic acetylcholine receptor CHRM1 (PubMed:10816588). {ECO:0000269|PubMed:10787416, ECO:0000269|PubMed:10816588, ECO:0000269|PubMed:11159685, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:28669405}. |
| Q9NRA8 | EIF4ENIF1 | S379 | ochoa | Eukaryotic translation initiation factor 4E transporter (4E-T) (eIF4E transporter) (Eukaryotic translation initiation factor 4E nuclear import factor 1) | EIF4E-binding protein that regulates translation and stability of mRNAs in processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:27342281, PubMed:32354837). Plays a key role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:24335285, PubMed:32354837). Acts as a binding platform for multiple RNA-binding proteins: promotes deadenylation of mRNAs via its interaction with the CCR4-NOT complex, and blocks decapping via interaction with eIF4E (EIF4E and EIF4E2), thereby protecting deadenylated and repressed mRNAs from degradation (PubMed:27342281, PubMed:32354837). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). Promotes miRNA-mediated translational repression (PubMed:24335285, PubMed:27342281, PubMed:28487484). Required for the formation of P-bodies (PubMed:16157702, PubMed:22966201, PubMed:27342281, PubMed:32354837). Involved in mRNA translational repression mediated by the miRNA effector TNRC6B by protecting TNRC6B-targeted mRNAs from decapping and subsequent decay (PubMed:32354837). Also acts as a nucleoplasmic shuttling protein, which mediates the nuclear import of EIF4E and DDX6 by a piggy-back mechanism (PubMed:10856257, PubMed:28216671). {ECO:0000250|UniProtKB:Q9EST3, ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:28216671, ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:32354837}. |
| Q9NRA8 | EIF4ENIF1 | S541 | ochoa | Eukaryotic translation initiation factor 4E transporter (4E-T) (eIF4E transporter) (Eukaryotic translation initiation factor 4E nuclear import factor 1) | EIF4E-binding protein that regulates translation and stability of mRNAs in processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:27342281, PubMed:32354837). Plays a key role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:24335285, PubMed:32354837). Acts as a binding platform for multiple RNA-binding proteins: promotes deadenylation of mRNAs via its interaction with the CCR4-NOT complex, and blocks decapping via interaction with eIF4E (EIF4E and EIF4E2), thereby protecting deadenylated and repressed mRNAs from degradation (PubMed:27342281, PubMed:32354837). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). Promotes miRNA-mediated translational repression (PubMed:24335285, PubMed:27342281, PubMed:28487484). Required for the formation of P-bodies (PubMed:16157702, PubMed:22966201, PubMed:27342281, PubMed:32354837). Involved in mRNA translational repression mediated by the miRNA effector TNRC6B by protecting TNRC6B-targeted mRNAs from decapping and subsequent decay (PubMed:32354837). Also acts as a nucleoplasmic shuttling protein, which mediates the nuclear import of EIF4E and DDX6 by a piggy-back mechanism (PubMed:10856257, PubMed:28216671). {ECO:0000250|UniProtKB:Q9EST3, ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:28216671, ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:32354837}. |
| Q9NRR3 | CDC42SE2 | S43 | ochoa | CDC42 small effector protein 2 (Small effector of CDC42 protein 2) | Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages. {ECO:0000269|PubMed:10816584, ECO:0000269|PubMed:15840583}. |
| Q9NRX5 | SERINC1 | S364 | ochoa | Serine incorporator 1 (Tumor differentially expressed protein 1-like) (Tumor differentially expressed protein 2) | Enhances the incorporation of serine into phosphatidylserine and sphingolipids. {ECO:0000250|UniProtKB:Q7TNK0}. |
| Q9NRY4 | ARHGAP35 | S770 | ochoa | Rho GTPase-activating protein 35 (Glucocorticoid receptor DNA-binding factor 1) (Glucocorticoid receptor repression factor 1) (GRF-1) (Rho GAP p190A) (p190-A) | Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}. |
| Q9NRY4 | ARHGAP35 | S1006 | ochoa | Rho GTPase-activating protein 35 (Glucocorticoid receptor DNA-binding factor 1) (Glucocorticoid receptor repression factor 1) (GRF-1) (Rho GAP p190A) (p190-A) | Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}. |
| Q9NSA2 | KCND1 | S555 | psp | A-type voltage-gated potassium channel KCND1 (Potassium voltage-gated channel subfamily D member 1) (Shal-type potassium channel KCND1) (Voltage-gated potassium channel subunit Kv4.1) | A-type voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes in the brain (PubMed:15454437). Mediates A-type current I(SA) in suprachiasmatic nucleus (SCN) neurons. Exhibits a low-threshold A-type current with a hyperpolarized steady-state inactivation midpoint and the recovery process was steeply voltage-dependent, with recovery being markedly faster at more negative potentials. May regulates repetitive firing rates in the suprachiasmatic nucleus (SCN) neurons and circadian rhythms in neuronal excitability and behavior. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity. The regulatory subunit KCNIP1 modulates the kinetics of channel inactivation, increases the current amplitudes and accelerates recovery from inactivation, shifts activation in a depolarizing direction (By similarity). The regulatory subunit DPP10 decreases the voltage sensitivity of the inactivation channel gating (PubMed:15454437). {ECO:0000250|UniProtKB:Q03719, ECO:0000269|PubMed:15454437}. |
| Q9NSI6 | BRWD1 | S1793 | ochoa | Bromodomain and WD repeat-containing protein 1 (WD repeat-containing protein 9) | May be a transcriptional activator. May be involved in chromatin remodeling (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| Q9NSY1 | BMP2K | S1111 | ochoa | BMP-2-inducible protein kinase (BIKe) (EC 2.7.11.1) | May be involved in osteoblast differentiation. {ECO:0000250|UniProtKB:Q91Z96}. |
| Q9NTM9 | CUTC | S224 | ochoa | Copper homeostasis protein cutC homolog | May play a role in copper homeostasis. Can bind one Cu(1+) per subunit. {ECO:0000269|PubMed:16182249, ECO:0000269|PubMed:19878721}. |
| Q9NTX5 | ECHDC1 | S54 | ochoa | Ethylmalonyl-CoA decarboxylase (EC 4.1.1.94) (Enoyl-CoA hydratase domain-containing protein 1) (Methylmalonyl-CoA decarboxylase) (MMCD) | Decarboxylates ethylmalonyl-CoA, a potentially toxic metabolite, to form butyryl-CoA, suggesting it might be involved in metabolite proofreading (PubMed:22016388). Acts preferentially on (S)-ethylmalonyl-CoA but also has some activity on the (R)-isomer (By similarity). Also has methylmalonyl-CoA decarboxylase activity at lower level (By similarity). {ECO:0000250|UniProtKB:Q9D9V3, ECO:0000269|PubMed:22016388}. |
| Q9NUL3 | STAU2 | S93 | ochoa | Double-stranded RNA-binding protein Staufen homolog 2 | RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity). {ECO:0000250|UniProtKB:Q68SB1}. |
| Q9NUL3 | STAU2 | S426 | ochoa | Double-stranded RNA-binding protein Staufen homolog 2 | RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity). {ECO:0000250|UniProtKB:Q68SB1}. |
| Q9NUQ8 | ABCF3 | S83 | ochoa | ATP-binding cassette sub-family F member 3 | Displays an antiviral effect against flaviviruses such as west Nile virus (WNV) in the presence of OAS1B. {ECO:0000250}. |
| Q9NUW8 | TDP1 | S365 | psp | Tyrosyl-DNA phosphodiesterase 1 (Tyr-DNA phosphodiesterase 1) (EC 3.1.4.-) | DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate. {ECO:0000269|PubMed:12023295, ECO:0000269|PubMed:15111055, ECO:0000269|PubMed:15811850, ECO:0000269|PubMed:16141202, ECO:0000269|PubMed:22822062}. |
| Q9NUY8 | TBC1D23 | S300 | ochoa | TBC1 domain family member 23 (HCV non-structural protein 4A-transactivated protein 1) | Putative Rab GTPase-activating protein which plays a role in vesicular trafficking (PubMed:28823707). Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197, PubMed:29426865). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). Plays a role in brain development, including in cortical neuron positioning (By similarity). May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth (By similarity). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (By similarity). {ECO:0000250|UniProtKB:Q8K0F1, ECO:0000269|PubMed:28823707, ECO:0000269|PubMed:29084197, ECO:0000269|PubMed:29426865}. |
| Q9NV56 | MRGBP | S149 | ochoa | MRG/MORF4L-binding protein (MRG-binding protein) (Up-regulated in colon cancer 4) (Urcc4) | Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. |
| Q9NV58 | RNF19A | S599 | ochoa | E3 ubiquitin-protein ligase RNF19A (EC 2.3.2.31) (Double ring-finger protein) (Dorfin) (RING finger protein 19A) (p38) | E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR. Specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation and to neuronal protection. {ECO:0000269|PubMed:11237715, ECO:0000269|PubMed:12145308, ECO:0000269|PubMed:12750386, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16513638}. |
| Q9NV88 | INTS9 | S564 | ochoa | Integrator complex subunit 9 (Int9) (Protein related to CPSF subunits of 74 kDa) (RC-74) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:25201415, PubMed:33243860, PubMed:33548203, PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:33243860, PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144, PubMed:22252320, PubMed:26308897, PubMed:30737432). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:22252320, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:25201415, ECO:0000269|PubMed:26308897, ECO:0000269|PubMed:30737432, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:33548203, ECO:0000269|PubMed:38570683}. |
| Q9NW75 | GPATCH2 | S359 | ochoa | G patch domain-containing protein 2 | Enhances the ATPase activity of DHX15 in vitro. {ECO:0000269|PubMed:19432882}. |
| Q9NWC5 | TMEM45A | S257 | ochoa | Transmembrane protein 45A (DNA polymerase-transactivated protein 4) (Dermal papilla-derived protein 7) | None |
| Q9NWM3 | CUEDC1 | S351 | ochoa | CUE domain-containing protein 1 | None |
| Q9NWV8 | BABAM1 | S62 | ochoa | BRISC and BRCA1-A complex member 1 (Mediator of RAP80 interactions and targeting subunit of 40 kDa) (New component of the BRCA1-A complex) | Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). {ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749}. |
| Q9NWW5 | CLN6 | S31 | ochoa | Ceroid-lipofuscinosis neuronal protein 6 (Protein CLN6) | None |
| Q9NX46 | ADPRS | S67 | ochoa | ADP-ribosylhydrolase ARH3 (ADP-ribose glycohydrolase ARH3) (ADP-ribosylhydrolase 3) (O-acetyl-ADP-ribose deacetylase ARH3) (EC 3.5.1.-) (Poly(ADP-ribose) glycohydrolase ARH3) (EC 3.2.1.143) ([Protein ADP-ribosylarginine] hydrolase-like protein 2) ([Protein ADP-ribosylserine] hydrolase) (EC 3.2.2.-) | ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:29907568, PubMed:30045870, PubMed:30401461, PubMed:30830864, PubMed:33186521, PubMed:33769608, PubMed:33894202, PubMed:34019811, PubMed:34321462, PubMed:34479984, PubMed:34625544). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521, PubMed:34019811, PubMed:34625544). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521, PubMed:34625544). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211, PubMed:33769608). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885). {ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:17075046, ECO:0000269|PubMed:21498885, ECO:0000269|PubMed:22433848, ECO:0000269|PubMed:28650317, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:29480802, ECO:0000269|PubMed:29907568, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:30401461, ECO:0000269|PubMed:30830864, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33769608, ECO:0000269|PubMed:33894202, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34321462, ECO:0000269|PubMed:34479984, ECO:0000269|PubMed:34625544}. |
| Q9NX94 | WBP1L | S199 | ochoa | WW domain binding protein 1-like (Outcome predictor in acute leukemia 1) | None |
| Q9NXB0 | MKS1 | S504 | ochoa | Tectonic-like complex member MKS1 (Meckel syndrome type 1 protein) | Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in centrosome migration to the apical cell surface during early ciliogenesis. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Required for cell branching morphology. {ECO:0000269|PubMed:17185389, ECO:0000269|PubMed:19515853, ECO:0000269|PubMed:26490104}. |
| Q9NXD2 | MTMR10 | S569 | ochoa | Myotubularin-related protein 10 (Inactive phosphatidylinositol 3-phosphatase 10) | None |
| Q9NXF1 | TEX10 | S287 | ochoa | Testis-expressed protein 10 | Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211). {ECO:0000269|PubMed:21326211, ECO:0000269|PubMed:22872859}. |
| Q9NXV6 | CDKN2AIP | S181 | ochoa | CDKN2A-interacting protein (Collaborator of ARF) | Regulates DNA damage response in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence. {ECO:0000269|PubMed:15109303, ECO:0000269|PubMed:24825908}. |
| Q9NY57 | STK32B | S378 | ochoa | Serine/threonine-protein kinase 32B (EC 2.7.11.1) (Yet another novel kinase 2) | None |
| Q9NY65 | TUBA8 | S379 | ochoa | Tubulin alpha-8 chain (EC 3.6.5.-) (Alpha-tubulin 8) (Tubulin alpha chain-like 2) [Cleaved into: Dephenylalaninated tubulin alpha-8 chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9NY74 | ETAA1 | S553 | ochoa | Ewing's tumor-associated antigen 1 (Ewing's tumor-associated antigen 16) | Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity (PubMed:27601467, PubMed:27723717, PubMed:27723720). Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1 (PubMed:27723717, PubMed:27723720, PubMed:30139873). Probably only regulates a subset of ATR targets (PubMed:27723717, PubMed:27723720). {ECO:0000269|PubMed:27601467, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873}. |
| Q9NYB9 | ABI2 | S368 | ochoa | Abl interactor 2 (Abelson interactor 2) (Abi-2) (Abl-binding protein 3) (AblBP3) (Arg-binding protein 1) (ArgBP1) | Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion. Functions as a component of the WAVE complex, which activates actin nucleating machinery Arp2/3 to drive lamellipodia formation (PubMed:21107423). Acts as a regulator and substrate of nonreceptor tyrosine kinases ABL1 and ABL2 involved in processes linked to cell growth and differentiation. Positively regulates ABL1-mediated phosphorylation of ENAH, which is required for proper polymerization of nucleated actin filaments at the leading edge (PubMed:10498863, PubMed:7590236, PubMed:8649853). Contributes to the regulation of actin assembly at the tips of neuron projections. In particular, controls dendritic spine morphogenesis and may promote dendritic spine specification toward large mushroom-type spines known as repositories of memory in the brain (By similarity). In hippocampal neurons, may mediate actin-dependent BDNF-NTRK2 early endocytic trafficking that triggers dendrite outgrowth (By similarity). Participates in ocular lens morphogenesis, likely by regulating lamellipodia-driven adherens junction formation at the epithelial cell-secondary lens fiber interface (By similarity). Also required for nascent adherens junction assembly in epithelial cells (PubMed:15572692). {ECO:0000250|UniProtKB:P62484, ECO:0000269|PubMed:10498863, ECO:0000269|PubMed:15572692, ECO:0000269|PubMed:21107423, ECO:0000269|PubMed:7590236, ECO:0000269|PubMed:8649853}. |
| Q9NYF5 | FAM13B | S760 | ochoa | Protein FAM13B (GAP-like protein N61) | None |
| Q9NYF8 | BCLAF1 | S427 | ochoa | Bcl-2-associated transcription factor 1 (Btf) (BCLAF1 and THRAP3 family member 1) | Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:18794151}. |
| Q9NYM9 | BET1L | S70 | ochoa | BET1-like protein (Golgi SNARE with a size of 15 kDa) (GOS-15) (GS15) (Vesicle transport protein GOS15) | Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex. Required for the integrity of the Golgi complex (By similarity). {ECO:0000250|UniProtKB:O35152}. |
| Q9NYP7 | ELOVL5 | S273 | ochoa | Very long chain fatty acid elongase 5 (EC 2.3.1.199) (3-keto acyl-CoA synthase ELOVL5) (ELOVL fatty acid elongase 5) (ELOVL FA elongase 5) (Elongation of very long chain fatty acids protein 5) (Fatty acid elongase 1) (hELO1) (Very long chain 3-ketoacyl-CoA synthase 5) (Very long chain 3-oxoacyl-CoA synthase 5) | Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate in the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators (By similarity) (PubMed:10970790, PubMed:20937905). In conditions where the essential linoleic and alpha linoleic fatty acids are lacking it is also involved in the synthesis of Mead acid from oleic acid (By similarity). {ECO:0000250|UniProtKB:Q8BHI7, ECO:0000255|HAMAP-Rule:MF_03205, ECO:0000269|PubMed:10970790, ECO:0000269|PubMed:20937905}. |
| Q9NYQ7 | CELSR3 | S3058 | ochoa | Cadherin EGF LAG seven-pass G-type receptor 3 (Cadherin family member 11) (Epidermal growth factor-like protein 1) (EGF-like protein 1) (Flamingo homolog 1) (hFmi1) (Multiple epidermal growth factor-like domains protein 2) (Multiple EGF-like domains protein 2) | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| Q9NZ09 | UBAP1 | S207 | ochoa | Ubiquitin-associated protein 1 (UBAP-1) (Nasopharyngeal carcinoma-associated gene 20 protein) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process (PubMed:21757351, PubMed:22405001, PubMed:31203368). Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) (PubMed:21757351, PubMed:22405001). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2 (PubMed:22405001, PubMed:24284069, PubMed:31203368). {ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22405001, ECO:0000269|PubMed:24284069, ECO:0000269|PubMed:31203368}. |
| Q9NZ53 | PODXL2 | S582 | ochoa | Podocalyxin-like protein 2 (Endoglycan) | Acts as a ligand for vascular selectins. Mediates rapid rolling of leukocytes over vascular surfaces through high affinity divalent cation-dependent interactions with E-, P- and L-selectins. {ECO:0000269|PubMed:18606703}. |
| Q9NZB2 | FAM120A | S1067 | ochoa | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q9NZN4 | EHD2 | S373 | ochoa | EH domain-containing protein 2 (PAST homolog 2) | ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis (By similarity). Plays a role in membrane trafficking between the plasma membrane and endosomes (PubMed:17233914). Important for the internalization of GLUT4. Required for fusion of myoblasts to skeletal muscle myotubes. Required for normal translocation of FER1L5 to the plasma membrane (By similarity). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by constraining caveolae at the cell membrane (PubMed:25588833). {ECO:0000250|UniProtKB:Q8BH64, ECO:0000269|PubMed:17233914, ECO:0000269|PubMed:25588833}. |
| Q9NZT2 | OGFR | S315 | ochoa | Opioid growth factor receptor (OGFr) (Protein 7-60) (Zeta-type opioid receptor) | Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation. |
| Q9NZT2 | OGFR | S423 | ochoa | Opioid growth factor receptor (OGFr) (Protein 7-60) (Zeta-type opioid receptor) | Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation. |
| Q9NZV8 | KCND2 | S552 | psp | A-type voltage-gated potassium channel KCND2 (Potassium voltage-gated channel subfamily D member 2) (Voltage-gated potassium channel subunit Kv4.2) | Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:11507158, PubMed:14623880, PubMed:14695263, PubMed:14980201, PubMed:15454437, PubMed:16934482, PubMed:19171772, PubMed:24501278, PubMed:24811166, PubMed:34552243, PubMed:35597238). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:14623880, PubMed:14980201, PubMed:15454437, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (PubMed:35597238). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10551270, ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278, ECO:0000269|PubMed:24811166, ECO:0000269|PubMed:34552243, ECO:0000269|PubMed:35597238}. |
| Q9P015 | MRPL15 | S33 | ochoa | Large ribosomal subunit protein uL15m (39S ribosomal protein L15, mitochondrial) (L15mt) (MRP-L15) | None |
| Q9P0J7 | KCMF1 | S145 | ochoa | E3 ubiquitin-protein ligase KCMF1 (EC 2.3.2.27) (FGF-induced in gastric cancer) (Potassium channel modulatory factor) (PCMF) (ZZ-type zinc finger-containing protein 1) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and then transfers it to targeted substrates, promoting their degradation by the proteasome (PubMed:15581609, PubMed:25582440, PubMed:34893540, PubMed:37891180, PubMed:38297121). Together with UBR4, component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR4, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). {ECO:0000269|PubMed:15581609, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38297121}. |
| Q9P0L0 | VAPA | S214 | ochoa | Vesicle-associated membrane protein-associated protein A (VAMP-A) (VAMP-associated protein A) (VAP-A) (33 kDa VAMP-associated protein) (VAP-33) | Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMed:32344433, PubMed:33124732). STARD3-VAPA interaction enables cholesterol transfer from the ER to endosomes (PubMed:33124732). Via interaction with WDR44 participates in neosynthesized protein export (PubMed:32344433). In addition, recruited to the plasma membrane through OSBPL3 binding (PubMed:25447204). The OSBPL3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER morphology (PubMed:16143324). May play a role in vesicle trafficking (PubMed:11511104, PubMed:19289470). {ECO:0000269|PubMed:11511104, ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:25447204, ECO:0000269|PubMed:32344433, ECO:0000269|PubMed:33124732}. |
| Q9P1Y5 | CAMSAP3 | S585 | ochoa | Calmodulin-regulated spectrin-associated protein 3 (Protein Nezha) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19041755, PubMed:23169647). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153). Required for the biogenesis and the maintenance of zonula adherens by anchoring the minus-end of microtubules to zonula adherens and by recruiting the kinesin KIFC3 to those junctional sites (PubMed:19041755). Required for orienting the apical-to-basal polarity of microtubules in epithelial cells: acts by tethering non-centrosomal microtubules to the apical cortex, leading to their longitudinal orientation (PubMed:26715742, PubMed:27802168). Plays a key role in early embryos, which lack centrosomes: accumulates at the microtubule bridges that connect pairs of cells and enables the formation of a non-centrosomal microtubule-organizing center that directs intracellular transport in the early embryo (By similarity). Couples non-centrosomal microtubules with actin: interaction with MACF1 at the minus ends of non-centrosomal microtubules, tethers the microtubules to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). Plays a key role in the generation of non-centrosomal microtubules by accumulating in the pericentrosomal region and cooperating with KATNA1 to release non-centrosomal microtubules from the centrosome (PubMed:28386021). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:28089391). Through interaction with AKAP9, involved in translocation of Golgi vesicles in epithelial cells, where microtubules are mainly non-centrosomal (PubMed:28089391). Plays an important role in motile cilia function by facilitatating proper orientation of basal bodies and formation of central microtubule pairs in motile cilia (By similarity). {ECO:0000250|UniProtKB:Q80VC9, ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:26715742, ECO:0000269|PubMed:27693509, ECO:0000269|PubMed:27802168, ECO:0000269|PubMed:28089391, ECO:0000269|PubMed:28386021}. |
| Q9P1Y6 | PHRF1 | S547 | ochoa | PHD and RING finger domain-containing protein 1 | None |
| Q9P212 | PLCE1 | S490 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (EC 3.1.4.11) (Pancreas-enriched phospholipase C) (Phosphoinositide phospholipase C-epsilon-1) (Phospholipase C-epsilon-1) (PLC-epsilon-1) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690). {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, ECO:0000269|PubMed:29058690}. |
| Q9P212 | PLCE1 | S1688 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (EC 3.1.4.11) (Pancreas-enriched phospholipase C) (Phosphoinositide phospholipase C-epsilon-1) (Phospholipase C-epsilon-1) (PLC-epsilon-1) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690). {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, ECO:0000269|PubMed:29058690}. |
| Q9P219 | CCDC88C | S2003 | ochoa | Protein Daple (Coiled-coil domain-containing protein 88C) (Dvl-associating protein with a high frequency of leucine residues) (hDaple) (Hook-related protein 2) (HkRP2) | Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation (PubMed:26126266). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical constriction of cells via ARHGEF18 (PubMed:30948426). {ECO:0000269|PubMed:26126266, ECO:0000269|PubMed:30948426}. |
| Q9P241 | ATP10D | S520 | ochoa | Phospholipid-transporting ATPase VD (EC 7.6.2.1) (ATPase class V type 10D) (P4-ATPase flippase complex alpha subunit ATP10D) | Catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of the plasma membrane. {ECO:0000269|PubMed:30530492}. |
| Q9P244 | LRFN1 | S646 | ochoa | Leucine-rich repeat and fibronectin type III domain-containing protein 1 (Synaptic adhesion-like molecule 2) | Promotes neurite outgrowth in hippocampal neurons. Involved in the regulation and maintenance of excitatory synapses. Induces the clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1, GRIA1 and GRIN1 (By similarity). {ECO:0000250}. |
| Q9P265 | DIP2B | S203 | ochoa | Disco-interacting protein 2 homolog B (DIP2 homolog B) | Negatively regulates axonal outgrowth and is essential for normal synaptic transmission. Not required for regulation of axon polarity. Promotes acetylation of alpha-tubulin. {ECO:0000250|UniProtKB:Q3UH60}. |
| Q9P265 | DIP2B | S255 | ochoa | Disco-interacting protein 2 homolog B (DIP2 homolog B) | Negatively regulates axonal outgrowth and is essential for normal synaptic transmission. Not required for regulation of axon polarity. Promotes acetylation of alpha-tubulin. {ECO:0000250|UniProtKB:Q3UH60}. |
| Q9P266 | JCAD | S680 | ochoa | Junctional cadherin 5-associated protein (Junctional protein associated with coronary artery disease) (JCAD) | None |
| Q9P273 | TENM3 | S116 | ochoa | Teneurin-3 (Ten-3) (Protein Odd Oz/ten-m homolog 3) (Tenascin-M3) (Ten-m3) (Teneurin transmembrane protein 3) | Involved in neural development by regulating the establishment of proper connectivity within the nervous system. Acts in both pre- and postsynaptic neurons in the hippocampus to control the assembly of a precise topographic projection: required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum, probably by promoting homophilic cell adhesion. Required for proper dendrite morphogenesis and axon targeting in the vertebrate visual system, thereby playing a key role in the development of the visual pathway. Regulates the formation in ipsilateral retinal mapping to both the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). May also be involved in the differentiation of the fibroblast-like cells in the superficial layer of mandibular condylar cartilage into chondrocytes. {ECO:0000250|UniProtKB:Q9WTS6}. |
| Q9P289 | STK26 | S34 | ochoa | Serine/threonine-protein kinase 26 (EC 2.7.11.1) (MST3 and SOK1-related kinase) (Mammalian STE20-like protein kinase 4) (MST-4) (STE20-like kinase MST4) (Serine/threonine-protein kinase MASK) | Serine/threonine-protein kinase that acts as a mediator of cell growth (PubMed:11641781, PubMed:17360971). Modulates apoptosis (PubMed:11641781, PubMed:17360971). In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Phosphorylates ATG4B at 'Ser-383', thereby increasing autophagic flux (PubMed:29232556). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:11641781, ECO:0000269|PubMed:17360971, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:27807006, ECO:0000269|PubMed:29232556}. |
| Q9P2D0 | IBTK | S1054 | ochoa | Inhibitor of Bruton tyrosine kinase (IBtk) | Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription. {ECO:0000269|PubMed:11577348}. |
| Q9P2D1 | CHD7 | S2229 | ochoa | Chromodomain-helicase-DNA-binding protein 7 (CHD-7) (EC 3.6.4.-) (ATP-dependent helicase CHD7) | ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Probable transcription regulator. May be involved in the in 45S precursor rRNA production. {ECO:0000269|PubMed:22646239, ECO:0000269|PubMed:28533432}. |
| Q9P2D1 | CHD7 | S2501 | ochoa | Chromodomain-helicase-DNA-binding protein 7 (CHD-7) (EC 3.6.4.-) (ATP-dependent helicase CHD7) | ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Probable transcription regulator. May be involved in the in 45S precursor rRNA production. {ECO:0000269|PubMed:22646239, ECO:0000269|PubMed:28533432}. |
| Q9P2D6 | FAM135A | S1385 | ochoa | Protein FAM135A | None |
| Q9P2E9 | RRBP1 | S659 | ochoa | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| Q9P2F8 | SIPA1L2 | S1286 | ochoa | Signal-induced proliferation-associated 1-like protein 2 (SIPA1-like protein 2) | None |
| Q9P2G1 | ANKIB1 | S438 | ochoa | Ankyrin repeat and IBR domain-containing protein 1 (EC 2.3.2.31) | Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. {ECO:0000250}. |
| Q9P2K8 | EIF2AK4 | S1515 | ochoa | eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}. |
| Q9P2N2 | ARHGAP28 | S65 | ochoa | Rho GTPase-activating protein 28 (Rho-type GTPase-activating protein 28) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}. |
| Q9P2N6 | KANSL3 | S559 | ochoa | KAT8 regulatory NSL complex subunit 3 (NSL complex protein NSL3) (Non-specific lethal 3 homolog) (Serum inhibited-related protein) (Testis development protein PRTD) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). Within the NSL complex, KANSL3 is required to promote KAT8 association with mitochondrial DNA (PubMed:27768893). Required for transcription of intraciliary transport genes in both ciliated and non-ciliated cells (By similarity). This is necessary for cilium assembly in ciliated cells and for organization of the microtubule cytoskeleton in non-ciliated cells (By similarity). Also required within the NSL complex to maintain nuclear architecture stability by promoting KAT8-mediated acetylation of lamin LMNA (By similarity). Plays an essential role in spindle assembly during mitosis (PubMed:26243146). Acts as a microtubule minus-end binding protein which stabilizes microtubules and promotes their assembly (PubMed:26243146). Indispensable during early embryonic development where it is required for proper lineage specification and maintenance during peri-implantation development and is essential for implantation (By similarity). {ECO:0000250|UniProtKB:A2RSY1, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}. |
| Q9UBC2 | EPS15L1 | S593 | ochoa | Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) | Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}. |
| Q9UBK2 | PPARGC1A | S273 | ochoa | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1-alpha) (PPAR-gamma coactivator 1-alpha) (PPARGC-1-alpha) (Ligand effect modulator 6) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:10713165, PubMed:20005308, PubMed:21376232, PubMed:28363985, PubMed:32433991). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:10713165, PubMed:20005308, PubMed:21376232). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:10713165, PubMed:20005308, PubMed:21376232). Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism (PubMed:10713165, PubMed:20005308, PubMed:21376232). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:16753578, PubMed:23142079). Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner (PubMed:23836911). Also involved in the integration of the circadian rhythms and energy metabolism (By similarity). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (By similarity). {ECO:0000250|UniProtKB:O70343, ECO:0000269|PubMed:10713165, ECO:0000269|PubMed:16753578, ECO:0000269|PubMed:20005308, ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:23836911, ECO:0000269|PubMed:28363985, ECO:0000269|PubMed:32433991}. |
| Q9UBL0 | ARPP21 | S421 | ochoa | cAMP-regulated phosphoprotein 21 (ARPP-21) (Thymocyte cAMP-regulated phosphoprotein) | Isoform 2 may act as a competitive inhibitor of calmodulin-dependent enzymes such as calcineurin in neurons. {ECO:0000250}. |
| Q9UBS3 | DNAJB9 | S133 | ochoa | DnaJ homolog subfamily B member 9 (Endoplasmic reticulum DNA J domain-containing protein 4) (ER-resident protein ERdj4) (ERdj4) (Microvascular endothelial differentiation gene 1 protein) (Mdg-1) | Co-chaperone for Hsp70 protein HSPA5/BiP that acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). J domain-containing co-chaperones stimulate the ATPase activity of Hsp70 proteins and are required for efficient substrate recognition by Hsp70 proteins (PubMed:18400946). In the unstressed endoplasmic reticulum, interacts with the luminal region of ERN1/IRE1 and selectively recruits HSPA5/BiP: HSPA5/BiP disrupts the dimerization of the active ERN1/IRE1 luminal region, thereby inactivating ERN1/IRE1 (By similarity). Also involved in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. Required for survival of B-cell progenitors and normal antibody production (By similarity). {ECO:0000250|UniProtKB:G3H0N9, ECO:0000250|UniProtKB:Q9QYI6, ECO:0000269|PubMed:18400946}. |
| Q9UBS8 | RNF14 | S175 | ochoa | E3 ubiquitin-protein ligase RNF14 (EC 2.3.2.31) (Androgen receptor-associated protein 54) (HFB30) (RING finger protein 14) | E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Recruited to stalled ribosomes by the ribosome collision sensor GCN1 and mediates 'Lys-6'-linked ubiquitination of target proteins, leading to their degradation (PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Mediates ubiquitination of EEF1A1/eEF1A and ETF1/eRF1 translation factors on stalled ribosomes, leading to their degradation (PubMed:36638793, PubMed:37651229). Also catalyzes ubiquitination of ribosomal proteins RPL0, RPL1, RPL12, RPS13 and RPS17 (PubMed:36638793). Specifically required to resolve RNA-protein cross-links caused by reactive aldehydes, which trigger translation stress by stalling ribosomes: acts by catalying 'Lys-6'-linked ubiquitination of RNA-protein cross-links, leading to their removal by the ATP-dependent unfoldase VCP and subsequent degradation by the proteasome (PubMed:37951215, PubMed:37951216). Independently of its function in the response to stalled ribosomes, acts as a regulator of transcription in Wnt signaling via its interaction with TCF transcription factors (TCF7/TCF1, TCF7L1/TCF3 and TCF7L2/TCF4) (PubMed:23449499). May also play a role as a coactivator for androgen- and, to a lesser extent, progesterone-dependent transcription (PubMed:19345326). {ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:23449499, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229, ECO:0000269|PubMed:37951215, ECO:0000269|PubMed:37951216}. |
| Q9UBS9 | SUCO | S1226 | ochoa | SUN domain-containing ossification factor (Membrane protein CH1) (Protein osteopotentia homolog) (SUN-like protein 1) | Required for bone modeling during late embryogenesis. Regulates type I collagen synthesis in osteoblasts during their postnatal maturation (By similarity). {ECO:0000250}. |
| Q9UBY5 | LPAR3 | S227 | ochoa | Lysophosphatidic acid receptor 3 (LPA receptor 3) (LPA-3) (Lysophosphatidic acid receptor Edg-7) | Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. May play a role in the development of ovarian cancer. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins. |
| Q9UBY9 | HSPB7 | S54 | ochoa | Heat shock protein beta-7 (HspB7) (Cardiovascular heat shock protein) (cvHsp) | None |
| Q9UDT6 | CLIP2 | S156 | ochoa | CAP-Gly domain-containing linker protein 2 (Cytoplasmic linker protein 115) (CLIP-115) (Cytoplasmic linker protein 2) (Williams-Beuren syndrome chromosomal region 3 protein) (Williams-Beuren syndrome chromosomal region 4 protein) | Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations (By similarity). {ECO:0000250}. |
| Q9UDY2 | TJP2 | S325 | ochoa | Tight junction protein 2 (Tight junction protein ZO-2) (Zona occludens protein 2) (Zonula occludens protein 2) | Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (By similarity). {ECO:0000250|UniProtKB:Q9Z0U1}. |
| Q9UEY8 | ADD3 | S360 | ochoa | Gamma-adducin (Adducin-like protein 70) | Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin (Probable). Involved in myogenic reactivity of the renal afferent arteriole (Af-art), renal interlobular arteries and middle cerebral artery (MCA) to increased perfusion pressure. Involved in regulation of potassium channels in the vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. Involved in regulation of glomerular capillary pressure, glomerular filtration rate (GFR) and glomerular nephrin expression in response to hypertension. Involved in renal blood flow (RBF) autoregulation. Plays a role in podocyte structure and function. Regulates globular monomer actin (G-actin) and filamentous polymer actin (F-actin) ratios in the primary podocytes affecting actin cytoskeleton organization. Regulates expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex and the primary podocytes. Regulates expression of nephrin in the glomeruli and in the primary podocytes, expression of nephrin and podocinin in the renal cortex, and expression of focal adhesion proteins integrin alpha-3 and integrin beta-1 in the glomeruli. Involved in cell migration and cell adhesion of podocytes, and in podocyte foot process effacement. Regulates expression of profibrotics markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E-cadherin, and mesenchymal markers vimentin and alpha-SMA (By similarity). Promotes the growth of neurites (By similarity). {ECO:0000250|UniProtKB:Q62847, ECO:0000250|UniProtKB:Q9QYB5, ECO:0000269|PubMed:23836506, ECO:0000305}. |
| Q9UFC0 | LRWD1 | S264 | ochoa | Leucine-rich repeat and WD repeat-containing protein 1 (Centromere protein 33) (CENP-33) (Origin recognition complex-associated protein) (ORC-associated protein) (ORCA) | Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability. {ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:20932478, ECO:0000269|PubMed:21029866, ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22645314}. |
| Q9UGI8 | TES | S140 | ochoa | Testin (TESS) | Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Plays a role in the regulation of cell proliferation. May act as a tumor suppressor. Inhibits tumor cell growth. {ECO:0000269|PubMed:11420696, ECO:0000269|PubMed:12571287, ECO:0000269|PubMed:12695497}. |
| Q9UGP4 | LIMD1 | S243 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UGP4 | LIMD1 | S413 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UGU0 | TCF20 | S884 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UGU5 | HMGXB4 | S166 | ochoa | HMG domain-containing protein 4 (HMG box-containing protein 4) (High mobility group protein 2-like 1) (Protein HMGBCG) | Negatively regulates Wnt/beta-catenin signaling during development. {ECO:0000250}. |
| Q9UH62 | ARMCX3 | S43 | ochoa | Armadillo repeat-containing X-linked protein 3 (ARM protein lost in epithelial cancers on chromosome X 3) (Protein ALEX3) | Regulates mitochondrial aggregation and transport in axons in living neurons. May link mitochondria to the TRAK2-kinesin motor complex via its interaction with Miro and TRAK2. Mitochondrial distribution and dynamics is regulated through ARMCX3 protein degradation, which is promoted by PCK and negatively regulated by WNT1. Enhances the SOX10-mediated transactivation of the neuronal acetylcholine receptor subunit alpha-3 and beta-4 subunit gene promoters. {ECO:0000250|UniProtKB:Q8BHS6}. |
| Q9UH99 | SUN2 | S110 | ochoa | SUN domain-containing protein 2 (Protein unc-84 homolog B) (Rab5-interacting protein) (Rab5IP) (Sad1/unc-84 protein-like 2) | As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5. {ECO:0000250|UniProtKB:Q8BJS4, ECO:0000269|PubMed:18396275, ECO:0000305}. |
| Q9UHF7 | TRPS1 | S1009 | ochoa | Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) | Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}. |
| Q9UHG0 | DCDC2 | S438 | ochoa | Doublecortin domain-containing protein 2 (Protein RU2S) | Protein that plays a role in the inhibition of canonical Wnt signaling pathway (PubMed:25557784). May be involved in neuronal migration during development of the cerebral neocortex (By similarity). Involved in the control of ciliogenesis and ciliary length (PubMed:25601850, PubMed:27319779). {ECO:0000250|UniProtKB:D3ZR10, ECO:0000269|PubMed:25557784, ECO:0000269|PubMed:25601850, ECO:0000269|PubMed:27319779}. |
| Q9UHG2 | PCSK1N | S206 | ochoa | ProSAAS (Proprotein convertase subtilisin/kexin type 1 inhibitor) (Proprotein convertase 1 inhibitor) (pro-SAAS) [Cleaved into: KEP; Big SAAS (b-SAAS); Little SAAS (l-SAAS) (N-proSAAS); Big PEN-LEN (b-PEN-LEN) (SAAS CT(1-49)); PEN; Little LEN (l-LEN); Big LEN (b-LEN) (SAAS CT(25-40))] | May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the further processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 84 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity (By similarity). {ECO:0000250|UniProtKB:Q9QXV0}.; FUNCTION: [Big LEN]: Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. {ECO:0000250|UniProtKB:Q9QXV0}.; FUNCTION: [PEN]: Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. {ECO:0000250|UniProtKB:Q9QXV0}. |
| Q9UHI6 | DDX20 | S703 | ochoa | Probable ATP-dependent RNA helicase DDX20 (EC 3.6.1.15) (EC 3.6.4.13) (Component of gems 3) (DEAD box protein 20) (DEAD box protein DP 103) (Gemin-3) | The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:18984161}. |
| Q9UHP3 | USP25 | S85 | ochoa | Ubiquitin carboxyl-terminal hydrolase 25 (EC 3.4.19.12) (Deubiquitinating enzyme 25) (USP on chromosome 21) (Ubiquitin thioesterase 25) (Ubiquitin-specific-processing protease 25) | Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions in various biological processes including inflammation and immune response (PubMed:29518389, PubMed:37683630). Modulates the Wnt/beta-catenin pathway by deubiquitinating and stabilizing tankyrases TNKS1 and TNKS2 (PubMed:28619731, PubMed:30926243, PubMed:38875478). Regulates KEAP1-NRF2 axis in the defense against oxidative assaults by deubiquitinating KEAP1 and protecting it from degradation leading to degradation of the NRF2 transcription factor that is responsible for mounting an anti-oxidation gene expression program (PubMed:37339955). Positively regulates RNA virus-induced innate signaling by interacting with and deubiquitinating ERLIN1 and ERLIN2 (PubMed:37683630). In turn, restricts virus production by regulating cholesterol biosynthetic flux (PubMed:37683630). Acts as a negative regulator of interleukin-17-mediated signaling and inflammation through the removal of 'Lys-63'-linked ubiquitination of TRAF5 and TRAF6 (PubMed:23042150). Prevents the ubiquitination and degradation of TRAF3 to reduce the phosphorylation levels of JNK and P38, the secretion of IL-1B and to induce endotoxin tolerance (PubMed:30579117). {ECO:0000269|PubMed:23042150, ECO:0000269|PubMed:28619731, ECO:0000269|PubMed:29518389, ECO:0000269|PubMed:30579117, ECO:0000269|PubMed:30926243, ECO:0000269|PubMed:37339955, ECO:0000269|PubMed:37683630, ECO:0000269|PubMed:38875478}.; FUNCTION: The muscle-specific isoform (USP25m) may have a role in the regulation of muscular differentiation and function. |
| Q9UHR4 | BAIAP2L1 | S354 | ochoa | BAR/IMD domain-containing adapter protein 2-like 1 (Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1) (BAI1-associated protein 2-like protein 1) (Insulin receptor tyrosine kinase substrate) | May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. {ECO:0000269|PubMed:17430976, ECO:0000269|PubMed:19366662, ECO:0000269|PubMed:22921828}. |
| Q9UHR6 | ZNHIT2 | S149 | ochoa | Zinc finger HIT domain-containing protein 2 (Protein FON) | May act as a bridging factor mediating the interaction between the R2TP/Prefoldin-like (R2TP/PFDL) complex and U5 small nuclear ribonucleoprotein (U5 snRNP) (PubMed:28561026). Required for the interaction of R2TP complex subunit RPAP3 and prefoldin-like subunit URI1 with U5 snRNP proteins EFTUD2 and PRPF8 (PubMed:28561026). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269|PubMed:28561026}. |
| Q9UHV7 | MED13 | S412 | ochoa | Mediator of RNA polymerase II transcription subunit 13 (Activator-recruited cofactor 250 kDa component) (ARC250) (Mediator complex subunit 13) (Thyroid hormone receptor-associated protein 1) (Thyroid hormone receptor-associated protein complex 240 kDa component) (Trap240) (Vitamin D3 receptor-interacting protein complex component DRIP250) (DRIP250) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269|PubMed:16595664}. |
| Q9UHV7 | MED13 | S859 | ochoa | Mediator of RNA polymerase II transcription subunit 13 (Activator-recruited cofactor 250 kDa component) (ARC250) (Mediator complex subunit 13) (Thyroid hormone receptor-associated protein 1) (Thyroid hormone receptor-associated protein complex 240 kDa component) (Trap240) (Vitamin D3 receptor-interacting protein complex component DRIP250) (DRIP250) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269|PubMed:16595664}. |
| Q9UHX1 | PUF60 | S445 | ochoa | Poly(U)-binding-splicing factor PUF60 (60 kDa poly(U)-binding-splicing factor) (FUSE-binding protein-interacting repressor) (FBP-interacting repressor) (Ro-binding protein 1) (RoBP1) (Siah-binding protein 1) (Siah-BP1) | DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with RO60. Binds to poly(U) RNA. {ECO:0000269|PubMed:10606266, ECO:0000269|PubMed:10882074, ECO:0000269|PubMed:11239393, ECO:0000269|PubMed:16452196, ECO:0000269|PubMed:16628215, ECO:0000269|PubMed:17579712}. |
| Q9UI40 | SLC24A2 | S333 | ochoa | Sodium/potassium/calcium exchanger 2 (Na(+)/K(+)/Ca(2+)-exchange protein 2) (Retinal cone Na-Ca+K exchanger) (Solute carrier family 24 member 2) | Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+) (PubMed:10662833, PubMed:26631410). Required for learming and memory by regulating neuronal Ca(2+), which is essential for the development of synaptic plasticity (By similarity). {ECO:0000250|UniProtKB:Q8BUN9, ECO:0000269|PubMed:10662833, ECO:0000269|PubMed:26631410}. |
| Q9UID3 | VPS51 | S640 | ochoa | Vacuolar protein sorting-associated protein 51 homolog (Another new gene 2 protein) (Protein fat-free homolog) | Acts as a component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome-derived carriers to the TGN (PubMed:20685960). Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061). {ECO:0000269|PubMed:20685960, ECO:0000269|PubMed:25799061}. |
| Q9UIG0 | BAZ1B | S57 | ochoa | Tyrosine-protein kinase BAZ1B (EC 2.7.10.2) (Bromodomain adjacent to zinc finger domain protein 1B) (Williams syndrome transcription factor) (Williams-Beuren syndrome chromosomal region 10 protein) (Williams-Beuren syndrome chromosomal region 9 protein) (hWALp2) | Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802, PubMed:19234442). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802, PubMed:19234442). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (PubMed:28801535). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (PubMed:15543136). {ECO:0000250|UniProtKB:Q9Z277, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:28801535}. |
| Q9UIG0 | BAZ1B | S312 | ochoa | Tyrosine-protein kinase BAZ1B (EC 2.7.10.2) (Bromodomain adjacent to zinc finger domain protein 1B) (Williams syndrome transcription factor) (Williams-Beuren syndrome chromosomal region 10 protein) (Williams-Beuren syndrome chromosomal region 9 protein) (hWALp2) | Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802, PubMed:19234442). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802, PubMed:19234442). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (PubMed:28801535). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (PubMed:15543136). {ECO:0000250|UniProtKB:Q9Z277, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:28801535}. |
| Q9UII2 | ATP5IF1 | S27 | psp | ATPase inhibitor, mitochondrial (ATP synthase F1 subunit epsilon) (Inhibitor of F(1)F(o)-ATPase) (IF(1)) (IF1) | Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase. Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing FECH to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme. {ECO:0000269|PubMed:12110673, ECO:0000269|PubMed:15528193, ECO:0000269|PubMed:19559621, ECO:0000269|PubMed:23135403}. |
| Q9UII2 | ATP5IF1 | S39 | ochoa|psp | ATPase inhibitor, mitochondrial (ATP synthase F1 subunit epsilon) (Inhibitor of F(1)F(o)-ATPase) (IF(1)) (IF1) | Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase. Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing FECH to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme. {ECO:0000269|PubMed:12110673, ECO:0000269|PubMed:15528193, ECO:0000269|PubMed:19559621, ECO:0000269|PubMed:23135403}. |
| Q9UJF2 | RASAL2 | S736 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UJF2 | RASAL2 | S899 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UJM3 | ERRFI1 | S256 | ochoa|psp | ERBB receptor feedback inhibitor 1 (Mitogen-inducible gene 6 protein) (MIG-6) | Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity). {ECO:0000250}. |
| Q9UJM8 | HAO1 | S65 | ochoa | 2-Hydroxyacid oxidase 1 (HAOX1) (EC 1.1.3.15) (Glycolate oxidase) (GO) (GOX) (Glyoxylate oxidase) (EC 1.2.3.5) | Broad substrate specificity (S)-2-hydroxy-acid oxidase that preferentially oxidizes glycolate (PubMed:10777549, PubMed:10978532, PubMed:17669354, PubMed:18215067). The glyoxylate produced by the oxidation of glycolate can then be utilized by alanine-glyoxylate aminotransferase for the peroxisomal synthesis of glycine; this pathway appears to be an important step for the detoxification of glyoxylate which, if allowed to accumulate, may be metabolized to oxalate with formation of kidney stones (PubMed:10978532, PubMed:17669354). Can also catalyze the oxidation of glyoxylate, and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate, albeit with much lower catalytic efficiency (PubMed:10777549, PubMed:17669354, PubMed:18215067). Active in vitro with the artificial electron acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be the physiological electron acceptor, leading to the production of H2O2 (PubMed:10777549, PubMed:10978532, PubMed:17669354, PubMed:18215067). Is not active on L-lactate and 2-hydroxybutanoate (PubMed:10777549). {ECO:0000269|PubMed:10777549, ECO:0000269|PubMed:10978532, ECO:0000269|PubMed:17669354, ECO:0000269|PubMed:18215067, ECO:0000303|PubMed:10978532, ECO:0000303|PubMed:17669354}. |
| Q9UJU6 | DBNL | S160 | ochoa | Drebrin-like protein (Cervical SH3P7) (Cervical mucin-associated protein) (Drebrin-F) (HPK1-interacting protein of 55 kDa) (HIP-55) (SH3 domain-containing protein 7) | Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis. Plays a role in the reorganization of the actin cytoskeleton, formation of cell projections, such as neurites, in neuron morphogenesis and synapse formation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for the formation of organized podosome rosettes (By similarity). May act as a common effector of antigen receptor-signaling pathways in leukocytes. Acts as a key component of the immunological synapse that regulates T-cell activation by bridging TCRs and the actin cytoskeleton to gene activation and endocytic processes. {ECO:0000250, ECO:0000269|PubMed:14729663}. |
| Q9UK32 | RPS6KA6 | S83 | ochoa | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| Q9UK59 | DBR1 | S474 | ochoa | Lariat debranching enzyme (EC 3.1.4.-) | Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover (PubMed:10982890, PubMed:16232320, PubMed:2435736). Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication via an RNA lariat intermediate in cDNA synthesis and have an antiviral cell-intrinsic defense function in the brainstem (PubMed:16232320, PubMed:29474921). {ECO:0000269|PubMed:10982890, ECO:0000269|PubMed:16232320, ECO:0000269|PubMed:2435736, ECO:0000269|PubMed:29474921}. |
| Q9UK76 | JPT1 | S28 | ochoa | Jupiter microtubule associated homolog 1 (Androgen-regulated protein 2) (Hematological and neurological expressed 1 protein) [Cleaved into: Jupiter microtubule associated homolog 1, N-terminally processed] | Modulates negatively AKT-mediated GSK3B signaling (PubMed:21323578, PubMed:22155408). Induces CTNNB1 'Ser-33' phosphorylation and degradation through the suppression of the inhibitory 'Ser-9' phosphorylation of GSK3B, which represses the function of the APC:CTNNB1:GSK3B complex and the interaction with CDH1/E-cadherin in adherent junctions (PubMed:25169422). Plays a role in the regulation of cell cycle and cell adhesion (PubMed:25169422, PubMed:25450365). Has an inhibitory role on AR-signaling pathway through the induction of receptor proteasomal degradation (PubMed:22155408). {ECO:0000269|PubMed:21323578, ECO:0000269|PubMed:22155408, ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:25450365}. |
| Q9UKA4 | AKAP11 | S239 | ochoa | A-kinase anchor protein 11 (AKAP-11) (A-kinase anchor protein 220 kDa) (AKAP 220) (hAKAP220) (Protein kinase A-anchoring protein 11) (PRKA11) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them. |
| Q9UKE5 | TNIK | S750 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
| Q9UKE5 | TNIK | S896 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
| Q9UKI8 | TLK1 | S74 | ochoa | Serine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (PKU-beta) (Tousled-like kinase 1) | Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}. |
| Q9UKJ3 | GPATCH8 | S650 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKJ3 | GPATCH8 | S653 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKK3 | PARP4 | S1511 | ochoa | Protein mono-ADP-ribosyltransferase PARP4 (EC 2.4.2.-) (193 kDa vault protein) (ADP-ribosyltransferase diphtheria toxin-like 4) (ARTD4) (PARP-related/IalphaI-related H5/proline-rich) (PH5P) (Poly [ADP-ribose] polymerase 4) (PARP-4) (Vault poly(ADP-ribose) polymerase) (VPARP) | Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. {ECO:0000269|PubMed:25043379}. |
| Q9UKM9 | RALY | S177 | ochoa | RNA-binding protein Raly (Autoantigen p542) (Heterogeneous nuclear ribonucleoprotein C-like 2) (hnRNP core protein C-like 2) (hnRNP associated with lethal yellow protein homolog) | RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver. Binds the lipid-responsive non-coding RNA LeXis and is required for LeXis-mediated effect on cholesterogenesis (By similarity). May be a heterogeneous nuclear ribonucleoprotein (hnRNP) (PubMed:9376072). {ECO:0000250|UniProtKB:Q64012, ECO:0000269|PubMed:9376072}. |
| Q9UKN8 | GTF3C4 | S122 | ochoa | General transcription factor 3C polypeptide 4 (EC 2.3.1.48) (TF3C-delta) (Transcription factor IIIC 90 kDa subunit) (TFIIIC 90 kDa subunit) (TFIIIC90) (Transcription factor IIIC subunit delta) | Essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA, tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin (PubMed:10523658). Has histone acetyltransferase activity (HAT) with unique specificity for free and nucleosomal H3 (PubMed:10523658). May cooperate with GTF3C5 in facilitating the recruitment of TFIIIB and RNA polymerase through direct interactions with BRF1, POLR3C and POLR3F (PubMed:10523658). May be localized close to the A box (PubMed:10523658). {ECO:0000269|PubMed:10523658}. |
| Q9UKT8 | FBXW2 | S245 | ochoa | F-box/WD repeat-containing protein 2 (F-box and WD-40 domain-containing protein 2) (Protein MD6) | Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. |
| Q9UKV8 | AGO2 | S828 | ochoa|psp | Protein argonaute-2 (Argonaute2) (hAgo2) (EC 3.1.26.n2) (Argonaute RISC catalytic component 2) (Eukaryotic translation initiation factor 2C 2) (eIF-2C 2) (eIF2C 2) (PAZ Piwi domain protein) (PPD) (Protein slicer) | Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. {ECO:0000250|UniProtKB:Q8CJG0, ECO:0000255|HAMAP-Rule:MF_03031, ECO:0000269|PubMed:15105377, ECO:0000269|PubMed:15260970, ECO:0000269|PubMed:15284456, ECO:0000269|PubMed:15337849, ECO:0000269|PubMed:15800637, ECO:0000269|PubMed:16081698, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16756390, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:17524464, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18048652, ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:18690212, ECO:0000269|PubMed:18771919, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:23746446, ECO:0000269|PubMed:37328606}.; FUNCTION: (Microbial infection) Upon Sars-CoV-2 infection, associates with viral miRNA-like small RNA, CoV2-miR-O7a, and may repress mRNAs, such as BATF2, to evade the IFN response. {ECO:0000269|PubMed:34903581}. |
| Q9UKZ4 | TENM1 | S105 | ochoa | Teneurin-1 (Ten-1) (Protein Odd Oz/ten-m homolog 1) (Tenascin-M1) (Ten-m1) (Teneurin transmembrane protein 1) [Cleaved into: Ten-1 intracellular domain (IDten-1) (Ten-1 ICD); Teneurin C-terminal-associated peptide (TCPA-1) (Ten-1 extracellular domain) (Ten-1 ECD)] | Involved in neural development, regulating the establishment of proper connectivity within the nervous system. May function as a cellular signal transducer (By similarity). {ECO:0000250}.; FUNCTION: [Teneurin C-terminal-associated peptide]: Plays a role in the regulation of neuroplasticity in the limbic system. Mediates a rapid reorganization of actin- and tubulin-based cytoskeleton elements with an increase in dendritic arborization and spine density formation of neurons in the hippocampus and amygdala. Induces BDNF transcription inhibition in neurons. Activates the mitogen-activated protein (MAP) kinase 2 (MEK2) and extracellular signal-regulated kinase (ERK) cascade. Also acts as a bioactive neuroprotective peptide on limbic neurons of the brain and regulates stress-induced behavior: attenuates alkalosis-associated necrotic cell death and the effects of corticotropin-releasing factor (CRF) on c-fos/FOS induction and on the reinstatement of cocaine seeking (By similarity). {ECO:0000250}.; FUNCTION: [Ten-1 intracellular domain]: Induces gene transcription activation. {ECO:0000250}. |
| Q9UL18 | AGO1 | S826 | ochoa | Protein argonaute-1 (Argonaute1) (hAgo1) (Argonaute RISC catalytic component 1) (Eukaryotic translation initiation factor 2C 1) (eIF-2C 1) (eIF2C 1) (Putative RNA-binding protein Q99) | Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:18771919}. |
| Q9UL63 | MKLN1 | S414 | ochoa | Muskelin | Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation (By similarity). Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1 (PubMed:18710924). {ECO:0000250|UniProtKB:O89050, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972}. |
| Q9ULC8 | ZDHHC8 | S286 | ochoa | Palmitoyltransferase ZDHHC8 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 8) (DHHC-8) (Zinc finger protein 378) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes (Probable). Through the palmitoylation of ABCA1 regulates the localization of the transporter to the plasma membrane and thereby regulates its function in cholesterol and phospholipid efflux (Probable). Could also pamitoylate the D(2) dopamine receptor DRD2 and regulate its stability and localization to the plasma membrane (Probable). Could also play a role in glutamatergic transmission (By similarity). {ECO:0000250|UniProtKB:Q5Y5T5, ECO:0000305|PubMed:19556522, ECO:0000305|PubMed:23034182, ECO:0000305|PubMed:26535572}.; FUNCTION: (Microbial infection) Able to palmitoylate SARS coronavirus-2/SARS-CoV-2 spike protein following its synthesis in the endoplasmic reticulum (ER). In the infected cell, promotes spike biogenesis by protecting it from premature ER degradation, increases half-life and controls the lipid organization of its immediate membrane environment. Once the virus has formed, spike palmitoylation controls fusion with the target cell. {ECO:0000269|PubMed:34599882}. |
| Q9ULD2 | MTUS1 | S279 | ochoa | Microtubule-associated tumor suppressor 1 (AT2 receptor-binding protein) (Angiotensin-II type 2 receptor-interacting protein) (Mitochondrial tumor suppressor 1) | Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}. |
| Q9ULD4 | BRPF3 | S959 | ochoa | Bromodomain and PHD finger-containing protein 3 | Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:26620551, PubMed:26677226). Plays a role in DNA replication initiation by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby facilitating the activation of replication origins (PubMed:26620551). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (PubMed:16387653). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:26620551, ECO:0000269|PubMed:26677226}. |
| Q9ULF5 | SLC39A10 | S570 | ochoa | Zinc transporter ZIP10 (Solute carrier family 39 member 10) (Zrt- and Irt-like protein 10) (ZIP-10) | Zinc-influx transporter (PubMed:17359283, PubMed:27274087, PubMed:30520657). When associated with SLC39A6, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT) (PubMed:23186163). SLC39A10-SLC39A6 heterodimers play also an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (PubMed:32797246). Plays an important for both mature B-cell maintenance and humoral immune responses (By similarity). When associated with SLC39A10, the heterodimer controls NCAM1 phosphorylation and integration into focal adhesion complexes during EMT (By similarity). {ECO:0000250|UniProtKB:Q6P5F6, ECO:0000269|PubMed:17359283, ECO:0000269|PubMed:23186163, ECO:0000269|PubMed:27274087, ECO:0000269|PubMed:30520657, ECO:0000269|PubMed:32797246}. |
| Q9ULH7 | MRTFB | S913 | ochoa | Myocardin-related transcription factor B (MRTF-B) (MKL/myocardin-like protein 2) (Megakaryoblastic leukemia 2) | Acts as a transcriptional coactivator of serum response factor (SRF). Required for skeletal myogenic differentiation. {ECO:0000269|PubMed:14565952}. |
| Q9ULI0 | ATAD2B | S79 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9ULI0 | ATAD2B | S372 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9ULI0 | ATAD2B | S1294 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9ULI3 | HEG1 | S1319 | ochoa | Protein HEG homolog 1 | Receptor component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions. {ECO:0000250}. |
| Q9ULI4 | KIF26A | S1256 | ochoa | Kinesin-like protein KIF26A | Atypical kinesin that plays a key role in enteric neuron development. Acts by repressing a cell growth signaling pathway in the enteric nervous system development, possibly via its interaction with GRB2 that prevents GRB2-binding to SHC, thereby attenating the GDNF-Ret signaling (By similarity). Binds to microtubules but lacks microtubule-based motility due to the absence of ATPase activity (By similarity). Plays a critical role in cerebral cortical development. It probably acts as a microtubule stabilizer that regulates neurite growth and radial migration of cortical excitatory neurons (PubMed:36228617). {ECO:0000250|UniProtKB:Q52KG5, ECO:0000269|PubMed:36228617}. |
| Q9ULJ3 | ZBTB21 | S324 | ochoa | Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) | Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}. |
| Q9ULM0 | PLEKHH1 | S84 | ochoa | Pleckstrin homology domain-containing family H member 1 (PH domain-containing family H member 1) | None |
| Q9ULS5 | TMCC3 | S46 | ochoa | Transmembrane and coiled-coil domain protein 3 | None |
| Q9ULS5 | TMCC3 | S242 | ochoa | Transmembrane and coiled-coil domain protein 3 | None |
| Q9ULT0 | TTC7A | S647 | ochoa | Tetratricopeptide repeat protein 7A (TPR repeat protein 7A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}. |
| Q9ULT8 | HECTD1 | S248 | ochoa | E3 ubiquitin-protein ligase HECTD1 (EC 2.3.2.26) (E3 ligase for inhibin receptor) (EULIR) (HECT domain-containing protein 1) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:33711283). Mediates 'Lys-63'-linked polyubiquitination of HSP90AA1 which leads to its intracellular localization and reduced secretion (By similarity). Negatively regulating HSP90AA1 secretion in cranial mesenchyme cells may impair their emigration and may be essential for the correct development of the cranial neural folds and neural tube closure (By similarity). Catalyzes ubiquitination and degradation of ZNF622, an assembly factor for the ribosomal 60S subunit, in hematopoietic cells, thereby promoting hematopoietic stem cell renewal (PubMed:33711283). {ECO:0000250|UniProtKB:Q69ZR2, ECO:0000269|PubMed:33711283}. |
| Q9ULT8 | HECTD1 | S1718 | ochoa | E3 ubiquitin-protein ligase HECTD1 (EC 2.3.2.26) (E3 ligase for inhibin receptor) (EULIR) (HECT domain-containing protein 1) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:33711283). Mediates 'Lys-63'-linked polyubiquitination of HSP90AA1 which leads to its intracellular localization and reduced secretion (By similarity). Negatively regulating HSP90AA1 secretion in cranial mesenchyme cells may impair their emigration and may be essential for the correct development of the cranial neural folds and neural tube closure (By similarity). Catalyzes ubiquitination and degradation of ZNF622, an assembly factor for the ribosomal 60S subunit, in hematopoietic cells, thereby promoting hematopoietic stem cell renewal (PubMed:33711283). {ECO:0000250|UniProtKB:Q69ZR2, ECO:0000269|PubMed:33711283}. |
| Q9ULU4 | ZMYND8 | S514 | ochoa | MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) | Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}. |
| Q9UMN6 | KMT2B | S782 | ochoa | Histone-lysine N-methyltransferase 2B (Lysine N-methyltransferase 2B) (EC 2.1.1.364) (Myeloid/lymphoid or mixed-lineage leukemia protein 4) (Trithorax homolog 2) (WW domain-binding protein 7) (WBP-7) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17707229, PubMed:25561738). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (PubMed:24081332). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250|UniProtKB:O08550, ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q9UMN6 | KMT2B | S2318 | ochoa | Histone-lysine N-methyltransferase 2B (Lysine N-methyltransferase 2B) (EC 2.1.1.364) (Myeloid/lymphoid or mixed-lineage leukemia protein 4) (Trithorax homolog 2) (WW domain-binding protein 7) (WBP-7) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17707229, PubMed:25561738). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (PubMed:24081332). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250|UniProtKB:O08550, ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q9UMZ2 | SYNRG | S730 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UMZ2 | SYNRG | S756 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UMZ2 | SYNRG | S919 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UN79 | SOX13 | S371 | ochoa | Transcription factor SOX-13 (Islet cell antigen 12) (SRY (Sex determining region Y)-box 13) (Type 1 diabetes autoantigen ICA12) | Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3' (PubMed:10871192). Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube (By similarity). Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells (By similarity). Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells (By similarity). Promotes brown adipocyte differentiation (By similarity). Inhibitor of WNT signaling (PubMed:20028982). {ECO:0000250|UniProtKB:Q04891, ECO:0000269|PubMed:10871192, ECO:0000269|PubMed:20028982}. |
| Q9UNS1 | TIMELESS | S105 | ochoa | Protein timeless homolog (hTIM) | Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:23418588, PubMed:26344098, PubMed:31138685, PubMed:32705708, PubMed:35585232, PubMed:9856465). Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:35585232). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (PubMed:23359676). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 (PubMed:32705708). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214, PubMed:31138685). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:31138685, PubMed:9856465). May play a role as destabilizer of the PER2-CRY2 complex (PubMed:31138685). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). {ECO:0000250|UniProtKB:Q9R1X4, ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31138685, ECO:0000269|PubMed:32705708, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9856465}. |
| Q9UNS1 | TIMELESS | S281 | ochoa | Protein timeless homolog (hTIM) | Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:23418588, PubMed:26344098, PubMed:31138685, PubMed:32705708, PubMed:35585232, PubMed:9856465). Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:35585232). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (PubMed:23359676). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 (PubMed:32705708). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214, PubMed:31138685). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:31138685, PubMed:9856465). May play a role as destabilizer of the PER2-CRY2 complex (PubMed:31138685). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). {ECO:0000250|UniProtKB:Q9R1X4, ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31138685, ECO:0000269|PubMed:32705708, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9856465}. |
| Q9UPN4 | CEP131 | S52 | ochoa | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9UPP1 | PHF8 | S722 | ochoa | Histone lysine demethylase PHF8 (EC 1.14.11.27) (EC 1.14.11.65) (PHD finger protein 8) ([histone H3]-dimethyl-L-lysine(36) demethylase PHF8) ([histone H3]-dimethyl-L-lysine(9) demethylase PHF8) | Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}. |
| Q9UPP1 | PHF8 | S793 | ochoa | Histone lysine demethylase PHF8 (EC 1.14.11.27) (EC 1.14.11.65) (PHD finger protein 8) ([histone H3]-dimethyl-L-lysine(36) demethylase PHF8) ([histone H3]-dimethyl-L-lysine(9) demethylase PHF8) | Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}. |
| Q9UPQ9 | TNRC6B | S1504 | ochoa | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}. |
| Q9UPU5 | USP24 | S911 | ochoa | Ubiquitin carboxyl-terminal hydrolase 24 (EC 3.4.19.12) (Deubiquitinating enzyme 24) (Ubiquitin thioesterase 24) (Ubiquitin-specific-processing protease 24) | Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}. |
| Q9UPU7 | TBC1D2B | S330 | ochoa | TBC1 domain family member 2B | GTPase-activating protein that plays a role in the early steps of endocytosis (PubMed:32623794). {ECO:0000269|PubMed:32623794}. |
| Q9UPV7 | PHF24 | S51 | ochoa | PHD finger protein 24 | None |
| Q9UQB8 | BAIAP2 | S446 | ochoa | BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) | Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}. |
| Q9UQB8 | BAIAP2 | S475 | ochoa | BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) | Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}. |
| Q9UQC2 | GAB2 | S281 | ochoa | GRB2-associated-binding protein 2 (GRB2-associated binder 2) (Growth factor receptor bound protein 2-associated protein 2) (pp100) | Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis. {ECO:0000269|PubMed:15750601, ECO:0000269|PubMed:19172738}. |
| Q9UQC2 | GAB2 | S459 | ochoa | GRB2-associated-binding protein 2 (GRB2-associated binder 2) (Growth factor receptor bound protein 2-associated protein 2) (pp100) | Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis. {ECO:0000269|PubMed:15750601, ECO:0000269|PubMed:19172738}. |
| Q9UQC2 | GAB2 | S474 | ochoa | GRB2-associated-binding protein 2 (GRB2-associated binder 2) (Growth factor receptor bound protein 2-associated protein 2) (pp100) | Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis. {ECO:0000269|PubMed:15750601, ECO:0000269|PubMed:19172738}. |
| Q9Y230 | RUVBL2 | S220 | ochoa | RuvB-like 2 (EC 3.6.4.12) (48 kDa TATA box-binding protein-interacting protein) (48 kDa TBP-interacting protein) (51 kDa erythrocyte cytosolic protein) (ECP-51) (INO80 complex subunit J) (Repressing pontin 52) (Reptin 52) (TIP49b) (TIP60-associated protein 54-beta) (TAP54-beta) | Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:11713276, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:25652260, ECO:0000269|PubMed:28561026, ECO:0000269|PubMed:33205750}. |
| Q9Y243 | AKT3 | S34 | ochoa | RAC-gamma serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-3) (Protein kinase B gamma) (PKB gamma) (RAC-PK-gamma) (STK-2) | AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. {ECO:0000269|PubMed:18524868, ECO:0000269|PubMed:21191416}. |
| Q9Y250 | LZTS1 | S117 | ochoa | Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucine-zipper motif) (Fez1) | Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}. |
| Q9Y250 | LZTS1 | S209 | ochoa | Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucine-zipper motif) (Fez1) | Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}. |
| Q9Y251 | HPSE | S426 | ochoa | Heparanase (EC 3.2.1.166) (Endo-glucoronidase) (Heparanase-1) (Hpa1) [Cleaved into: Heparanase 8 kDa subunit; Heparanase 50 kDa subunit] | Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as a procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis. {ECO:0000269|PubMed:12213822, ECO:0000269|PubMed:12773484, ECO:0000269|PubMed:15044433, ECO:0000269|PubMed:16452201, ECO:0000269|PubMed:18557927, ECO:0000269|PubMed:18798279, ECO:0000269|PubMed:19244131, ECO:0000269|PubMed:20097882, ECO:0000269|PubMed:20181948, ECO:0000269|PubMed:20309870, ECO:0000269|PubMed:20561914, ECO:0000269|PubMed:21131364}. |
| Q9Y266 | NUDC | S136 | ochoa | Nuclear migration protein nudC (Nuclear distribution protein C homolog) | Plays a role in neurogenesis and neuronal migration (By similarity). Necessary for correct formation of mitotic spindles and chromosome separation during mitosis (PubMed:12679384, PubMed:12852857, PubMed:25789526). Necessary for cytokinesis and cell proliferation (PubMed:12679384, PubMed:12852857). {ECO:0000250|UniProtKB:O35685, ECO:0000269|PubMed:12679384, ECO:0000269|PubMed:12852857, ECO:0000269|PubMed:25789526}. |
| Q9Y267 | SLC22A14 | S198 | ochoa | Solute carrier family 22 member 14 (Organic cation transporter-like 4) (ORCTL-4) | Riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa midpiece, which is required for male fertility (By similarity). SLC22A14-mediated riboflavin transport is essential for spermatozoa energy generation and motility: riboflavin is the precursor of FMN and FAD, which are coenzymes of many enzymes in the TCA cycle (the citric acid cycle) in mitochondria (By similarity). Required for sperm motility and normal sperm flagellar structure (By similarity). {ECO:0000250|UniProtKB:Q497L9}. |
| Q9Y2D9 | ZNF652 | S57 | ochoa | Zinc finger protein 652 | Functions as a transcriptional repressor. {ECO:0000269|PubMed:16966434}. |
| Q9Y2F5 | ICE1 | S546 | ochoa | Little elongation complex subunit 1 (Interactor of little elongator complex ELL subunit 1) | Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (PubMed:23932780). {ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23932780}. |
| Q9Y2H6 | FNDC3A | S234 | ochoa | Fibronectin type-III domain-containing protein 3A (Human gene expressed in odontoblasts) | Mediates spermatid-Sertoli adhesion during spermatogenesis. {ECO:0000250}. |
| Q9Y2I7 | PIKFYVE | S257 | ochoa | 1-phosphatidylinositol 3-phosphate 5-kinase (Phosphatidylinositol 3-phosphate 5-kinase) (EC 2.7.1.150) (FYVE finger-containing phosphoinositide kinase) (PIKfyve) (Phosphatidylinositol 3-phosphate 5-kinase type III) (PIPkin-III) (Type III PIP kinase) (Serine-protein kinase PIKFYVE) (EC 2.7.11.1) | Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:23086417). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:17556371). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:22621786). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:33098764). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (PubMed:30612035). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (By similarity). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (PubMed:30612035). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (By similarity). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, through association with SPAG9 and RABEPK (By similarity). Mediates EGFR trafficking to the nucleus (PubMed:17909029). {ECO:0000250|UniProtKB:Q9Z1T6, ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:22621786, ECO:0000269|PubMed:27623384, ECO:0000269|PubMed:28779020, ECO:0000269|PubMed:29584722, ECO:0000269|PubMed:30612035, ECO:0000269|PubMed:33098764, ECO:0000303|PubMed:23086417}.; FUNCTION: (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC) by endocytosis. {ECO:0000269|PubMed:32221306}. |
| Q9Y2J4 | AMOTL2 | S50 | ochoa | Angiomotin-like protein 2 (Leman coiled-coil protein) (LCCP) | Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments. Plays a role in coupling actin fibers to cell junctions in endothelial cells and is therefore required for correct endothelial cell morphology via facilitating transcellular transmission of mechanical force resulting in endothelial cell elongation (By similarity). Required for the anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane which facilitates organization of radial actin fiber structure and cellular response to contractile forces (PubMed:28842668). This contributes to maintenance of cell area, size, shape, epithelial sheet organization and trophectoderm cell properties that facilitate blastocyst zona hatching (PubMed:28842668). Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. Activates the Hippo signaling pathway in response to cell contact inhibition via interaction with and ubiquitination by Crumbs complex-bound WWP1 (PubMed:34404733). Ubiquitinated AMOTL2 then interacts with LATS2 which in turn phosphorylates YAP1, excluding it from the nucleus and localizing it to the cytoplasm and tight junctions, therefore ultimately repressing YAP1-driven transcription of target genes (PubMed:17293535, PubMed:21205866, PubMed:26598551). Acts to inhibit WWTR1/TAZ transcriptional coactivator activity via sequestering WWTR1/TAZ in the cytoplasm and at tight junctions (PubMed:23911299). Regulates the size and protein composition of the podosome cortex and core at myofibril neuromuscular junctions (PubMed:23525008). Selectively promotes FGF-induced MAPK activation through SRC (PubMed:17293535). May play a role in the polarity, proliferation and migration of endothelial cells. {ECO:0000250|UniProtKB:Q8K371, ECO:0000269|PubMed:17293535, ECO:0000269|PubMed:21205866, ECO:0000269|PubMed:21937427, ECO:0000269|PubMed:22362771, ECO:0000269|PubMed:23525008, ECO:0000269|PubMed:23911299, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:28842668, ECO:0000269|PubMed:34404733}. |
| Q9Y2K6 | USP20 | S854 | ochoa | Ubiquitin carboxyl-terminal hydrolase 20 (EC 3.4.19.12) (Deubiquitinating enzyme 20) (Ubiquitin thioesterase 20) (Ubiquitin-specific-processing protease 20) (VHL-interacting deubiquitinating enzyme 2) (hVDU2) | Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis (PubMed:27801882, PubMed:29487085). Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination (PubMed:26839314). Promotes cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'-linked ubiquitination of STING1 leading to its stabilization (PubMed:27801882). Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1 (PubMed:29487085). Acts as a positive regulator for NF-kappa-B activation by TNF-alpha through deubiquitinating 'Lys-48'-linked polyubiquitination of SQSTM1, leading to its increased stability (PubMed:32354117). Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2) (PubMed:19424180). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2 (PubMed:19424180). This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity (PubMed:15776016). Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability (PubMed:35063767). Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol (PubMed:33792613). {ECO:0000269|PubMed:12056827, ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:15776016, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:26839314, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:33792613, ECO:0000269|PubMed:35063767}. |
| Q9Y2L5 | TRAPPC8 | S311 | ochoa | Trafficking protein particle complex subunit 8 (Protein TRS85 homolog) | Plays a role in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage (PubMed:21525244). Maintains together with TBC1D14 the cycling pool of ATG9 required for initiation of autophagy (PubMed:26711178). Involved in collagen secretion (PubMed:32095531). {ECO:0000269|PubMed:21525244, ECO:0000269|PubMed:26711178, ECO:0000269|PubMed:32095531}. |
| Q9Y2Q9 | MRPS28 | S73 | ochoa | Small ribosomal subunit protein bS1m (28S ribosomal protein S28, mitochondrial) (MRP-S28) (S28mt) (28S ribosomal protein S35, mitochondrial) (MRP-S35) (S35mt) | None |
| Q9Y2R2 | PTPN22 | S419 | ochoa | Tyrosine-protein phosphatase non-receptor type 22 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP) (Lymphoid phosphatase) (LyP) (PEST-domain phosphatase) (PEP) | Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr-493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106). Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of 'Tyr-861' of NLRP3 (PubMed:27043286). Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (By similarity). {ECO:0000250|UniProtKB:P29352, ECO:0000269|PubMed:16461343, ECO:0000269|PubMed:18056643, ECO:0000269|PubMed:19167335, ECO:0000269|PubMed:21719704, ECO:0000269|PubMed:23871208, ECO:0000269|PubMed:23991106, ECO:0000269|PubMed:27043286}. |
| Q9Y2S7 | POLDIP2 | S290 | ochoa | Polymerase delta-interacting protein 2 (38 kDa DNA polymerase delta interaction protein) (p38) | Involved in DNA damage tolerance by regulating translesion synthesis (TLS) of templates carrying DNA damage lesions such as 8oxoG and abasic sites (PubMed:24191025). May act by stimulating activity of DNA polymerases involved in TLS, such as PRIMPOL and polymerase delta (POLD1) (PubMed:24191025, PubMed:26984527). {ECO:0000269|PubMed:24191025, ECO:0000269|PubMed:26984527}. |
| Q9Y2T2 | AP3M1 | S150 | ochoa | AP-3 complex subunit mu-1 (AP-3 adaptor complex mu3A subunit) (Adaptor-related protein complex 3 subunit mu-1) (Mu-adaptin 3A) (Mu3A-adaptin) | Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. |
| Q9Y2U8 | LEMD3 | S327 | ochoa | Inner nuclear membrane protein Man1 (LEM domain-containing protein 3) | Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271}. |
| Q9Y2W1 | THRAP3 | S891 | ochoa | Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) | Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| Q9Y2X3 | NOP58 | S304 | ochoa | Nucleolar protein 58 (Nucleolar protein 5) | Required for the biogenesis of box C/D snoRNAs such as U3, U8 and U14 snoRNAs (PubMed:15574333, PubMed:17636026, PubMed:19620283, PubMed:34516797). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:39570315). {ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:19620283, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| Q9Y2X7 | GIT1 | S498 | ochoa|psp | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y2X8 | UBE2D4 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D4 (EC 2.3.2.23) (E2 ubiquitin-conjugating enzyme D4) (HBUCE1) (Ubiquitin carrier protein D4) (Ubiquitin-protein ligase D4) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11' and 'Lys-48'-linked polyubiquitination. {ECO:0000269|PubMed:20061386}. |
| Q9Y2X9 | ZNF281 | S402 | ochoa | Zinc finger protein 281 (GC-box-binding zinc finger protein 1) (Transcription factor ZBP-99) (Zinc finger DNA-binding protein 99) | Transcription repressor that plays a role in regulation of embryonic stem cells (ESCs) differentiation. Required for ESCs differentiation and acts by mediating autorepression of NANOG in ESCs: binds to the NANOG promoter and promotes association of NANOG protein to its own promoter and recruits the NuRD complex, which deacetylates histones. Not required for establishement and maintenance of ESCs (By similarity). Represses the transcription of a number of genes including GAST, ODC1 and VIM. Binds to the G-rich box in the enhancer region of these genes. {ECO:0000250, ECO:0000269|PubMed:10448078, ECO:0000269|PubMed:12771217}. |
| Q9Y2X9 | ZNF281 | S683 | ochoa | Zinc finger protein 281 (GC-box-binding zinc finger protein 1) (Transcription factor ZBP-99) (Zinc finger DNA-binding protein 99) | Transcription repressor that plays a role in regulation of embryonic stem cells (ESCs) differentiation. Required for ESCs differentiation and acts by mediating autorepression of NANOG in ESCs: binds to the NANOG promoter and promotes association of NANOG protein to its own promoter and recruits the NuRD complex, which deacetylates histones. Not required for establishement and maintenance of ESCs (By similarity). Represses the transcription of a number of genes including GAST, ODC1 and VIM. Binds to the G-rich box in the enhancer region of these genes. {ECO:0000250, ECO:0000269|PubMed:10448078, ECO:0000269|PubMed:12771217}. |
| Q9Y2Y9 | KLF13 | S268 | ochoa | Krueppel-like factor 13 (Basic transcription element-binding protein 3) (BTE-binding protein 3) (Novel Sp1-like zinc finger transcription factor 1) (RANTES factor of late activated T-lymphocytes 1) (RFLAT-1) (Transcription factor BTEB3) (Transcription factor NSLP1) | Transcription factor that activates expression from GC-rich minimal promoter regions, including genes in the cells of the erythroid lineage (By similarity). Represses transcription by binding to the BTE site, a GC-rich DNA element, in competition with the activator SP1. It also represses transcription by interacting with the corepressor Sin3A and HDAC1 (PubMed:11477107). Activates RANTES and CCL5 expression in T-cells (PubMed:17513757). {ECO:0000250|UniProtKB:Q9JJZ6, ECO:0000269|PubMed:11477107, ECO:0000269|PubMed:17513757}. |
| Q9Y343 | SNX24 | S116 | ochoa | Sorting nexin-24 | May be involved in several stages of intracellular trafficking. {ECO:0000250}. |
| Q9Y3F4 | STRAP | S179 | psp | Serine-threonine kinase receptor-associated protein (MAP activator with WD repeats) (UNR-interacting protein) (WD-40 repeat protein PT-WD) | The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein. {ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:18984161}. |
| Q9Y3L3 | SH3BP1 | S17 | ochoa | SH3 domain-binding protein 1 | GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration (PubMed:21658605). Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions (PubMed:22891260). Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment (PubMed:26465210). It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin-plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (PubMed:24841563). {ECO:0000269|PubMed:21658605, ECO:0000269|PubMed:22891260, ECO:0000269|PubMed:24841563, ECO:0000269|PubMed:26465210}. |
| Q9Y3Q8 | TSC22D4 | S225 | ochoa | TSC22 domain family protein 4 (TSC22-related-inducible leucine zipper protein 2) | Binds DNA and acts as a transcriptional repressor (PubMed:10488076). Involved in the regulation of systematic glucose homeostasis and insulin sensitivity, via transcriptional repression of downstream insulin signaling targets such as OBP2A/LCN13 (By similarity). Acts as a negative regulator of lipogenic gene expression in hepatocytes and thereby mediates the control of very low-density lipoprotein release (PubMed:23307490). May play a role in neurite elongation and survival (By similarity). {ECO:0000250|UniProtKB:Q9EQN3, ECO:0000269|PubMed:10488076, ECO:0000269|PubMed:23307490}. |
| Q9Y446 | PKP3 | S172 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y446 | PKP3 | S305 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y448 | KNSTRN | S232 | ochoa | Small kinetochore-associated protein (SKAP) (Kinetochore-localized astrin-binding protein) (Kinastrin) (Kinetochore-localized astrin/SPAG5-binding protein) (TRAF4-associated factor 1) | Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase (PubMed:19667759). Promotes the metaphase-to-anaphase transition and is required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:19667759, PubMed:22110139). The astrin (SPAG5)-kinastrin (SKAP) complex promotes stable microtubule-kinetochore attachments (PubMed:21402792). Required for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis, possibly by forming a link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division (PubMed:23035123). May be involved in UV-induced apoptosis via its interaction with PRPF19; however, these results need additional evidences (PubMed:24718257). {ECO:0000269|PubMed:19667759, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:22110139, ECO:0000269|PubMed:23035123, ECO:0000305|PubMed:24718257}. |
| Q9Y485 | DMXL1 | S1830 | ochoa | DmX-like protein 1 (X-like 1 protein) | None |
| Q9Y487 | ATP6V0A2 | S704 | ochoa | V-type proton ATPase 116 kDa subunit a 2 (V-ATPase 116 kDa subunit a 2) (Lysosomal H(+)-transporting ATPase V0 subunit a 2) (TJ6) (Vacuolar proton translocating ATPase 116 kDa subunit a isoform 2) | Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Essential component of the endosomal pH-sensing machinery (PubMed:16415858). May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH (PubMed:18157129). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). {ECO:0000250|UniProtKB:Q29466, ECO:0000250|UniProtKB:Q93050, ECO:0000269|PubMed:16415858, ECO:0000269|PubMed:18157129, ECO:0000269|PubMed:28296633}. |
| Q9Y490 | TLN1 | S446 | ochoa|psp | Talin-1 | High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane. With KANK1 co-organize the assembly of cortical microtubule stabilizing complexes (CMSCs) positioned to control microtubule-actin crosstalk at focal adhesions (FAs) rims. {ECO:0000250|UniProtKB:P26039}. |
| Q9Y490 | TLN1 | S604 | ochoa | Talin-1 | High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane. With KANK1 co-organize the assembly of cortical microtubule stabilizing complexes (CMSCs) positioned to control microtubule-actin crosstalk at focal adhesions (FAs) rims. {ECO:0000250|UniProtKB:P26039}. |
| Q9Y4B5 | MTCL1 | S911 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4B5 | MTCL1 | S1284 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4B5 | MTCL1 | S1302 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4E5 | ZNF451 | S825 | ochoa | E3 SUMO-protein ligase ZNF451 (EC 2.3.2.-) (Coactivator for steroid receptors) (E3 SUMO-protein transferase ZNF451) (Zinc finger protein 451) | E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins (PubMed:26524493, PubMed:26524494). Plays a role in protein SUMO2 modification in response to stress caused by DNA damage and by proteasome inhibitors (in vitro). Required for MCM4 sumoylation (By similarity). Has no activity with SUMO1 (PubMed:26524493). Preferentially transfers an additional SUMO2 chain onto the SUMO2 consensus site 'Lys-11' (PubMed:26524493). Negatively regulates transcriptional activation mediated by the SMAD4 complex in response to TGF-beta signaling. Inhibits EP300-mediated acetylation of histone H3 at 'Lys-9' (PubMed:24324267). Plays a role in regulating the transcription of AR targets (PubMed:18656483). {ECO:0000250|UniProtKB:Q8C0P7, ECO:0000269|PubMed:18656483, ECO:0000269|PubMed:24324267, ECO:0000269|PubMed:26524493, ECO:0000269|PubMed:26524494}. |
| Q9Y4G8 | RAPGEF2 | S930 | ochoa | Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) | Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}. |
| Q9Y4G8 | RAPGEF2 | S1095 | ochoa | Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) | Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}. |
| Q9Y4L1 | HYOU1 | S634 | ochoa | Hypoxia up-regulated protein 1 (150 kDa oxygen-regulated protein) (ORP-150) (170 kDa glucose-regulated protein) (GRP-170) (Heat shock protein family H member 4) | Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. Promotes HSPA5/BiP-mediated ATP nucleotide exchange and thereby activates the unfolded protein response (UPR) pathway in the presence of endoplasmic reticulum stress (By similarity). May play a role as a molecular chaperone and participate in protein folding. {ECO:0000250|UniProtKB:Q9JKR6, ECO:0000269|PubMed:10037731}. |
| Q9Y4P3 | TBL2 | S352 | ochoa | Transducin beta-like protein 2 (WS beta-transducin repeats protein) (WS-betaTRP) (Williams-Beuren syndrome chromosomal region 13 protein) | None |
| Q9Y4P8 | WIPI2 | S390 | ochoa | WD repeat domain phosphoinositide-interacting protein 2 (WIPI-2) (WIPI49-like protein 2) | Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:20505359, PubMed:28561066). Involved in an early step of the formation of preautophagosomal structures (PubMed:20505359, PubMed:28561066). Binds and is activated by phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases (PubMed:28561066). Mediates ER-isolation membranes contacts by interacting with the ULK1:RB1CC1 complex and PtdIns3P (PubMed:28890335). Once activated, WIPI2 recruits at phagophore assembly sites the ATG12-ATG5-ATG16L1 complex that directly controls the elongation of the nascent autophagosomal membrane (PubMed:20505359, PubMed:28561066). {ECO:0000269|PubMed:20505359, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:30968111}.; FUNCTION: [Isoform 4]: Recruits the ATG12-ATG5-ATG16L1 complex to omegasomes and preautophagosomal structures, resulting in ATG8 family proteins lipidation and starvation-induced autophagy. Isoform 4 is also required for autophagic clearance of pathogenic bacteria. Isoform 4 binds the membrane surrounding Salmonella and recruits the ATG12-5-16L1 complex, initiating LC3 conjugation, autophagosomal membrane formation, and engulfment of Salmonella. {ECO:0000269|PubMed:24954904}. |
| Q9Y570 | PPME1 | S22 | ochoa | Protein phosphatase methylesterase 1 (PME-1) (EC 3.1.1.89) | Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme. {ECO:0000269|PubMed:10318862}. |
| Q9Y580 | RBM7 | S224 | ochoa | RNA-binding protein 7 (RNA-binding motif protein 7) | RNA-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:25189701, PubMed:25525152, PubMed:25578728, PubMed:25852104, PubMed:27871484). NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:25189701, PubMed:25852104, PubMed:27871484). Binds preferentially polyuridine sequences and associates with newly synthesized RNAs, including pre-mRNAs and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from small nuclear RNAs (snRNAs) (PubMed:25189701, PubMed:25525152, PubMed:25578728, PubMed:25852104). Participates in several biological processes including DNA damage response (DDR) and stress response (PubMed:25525152, PubMed:30824372). During stress response, activation of the p38MAPK-MK2 pathway decreases RBM7-RNA-binding and subsequently the RNA exosome degradation activities, thereby modulating the turnover of non-coding transcriptome (PubMed:25525152). Participates in DNA damage response (DDR), through its interaction with MEPCE and LARP7, the core subunits of 7SK snRNP complex, that release the positive transcription elongation factor b (P-TEFb) complex from the 7SK snRNP. In turn, activation of P-TEFb complex induces the transcription of P-TEFb-dependent DDR genes to promote cell viability (PubMed:30824372). {ECO:0000269|PubMed:25189701, ECO:0000269|PubMed:25525152, ECO:0000269|PubMed:25578728, ECO:0000269|PubMed:25852104, ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:30824372}. |
| Q9Y5A9 | YTHDF2 | S213 | ochoa | YTH domain-containing family protein 2 (DF2) (CLL-associated antigen KW-14) (High-glucose-regulated protein 8) (Renal carcinoma antigen NY-REN-2) | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:25412658, PubMed:25412661, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31292544, PubMed:31388144, PubMed:31642031, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440). {ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658, ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30065315, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:30930054, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:31642031, ECO:0000269|PubMed:31815440, ECO:0000269|PubMed:32169943, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282). {ECO:0000269|PubMed:29447282}.; FUNCTION: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}. |
| Q9Y5M8 | SRPRB | S174 | ochoa | Signal recognition particle receptor subunit beta (SR-beta) (Protein APMCF1) | Component of the signal recognition particle (SRP) complex receptor (SR) (By similarity). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (By similarity). May mediate the membrane association of SR (By similarity). {ECO:0000250|UniProtKB:P47758}. |
| Q9Y5U4 | INSIG2 | S151 | psp | Insulin-induced gene 2 protein (INSIG-2) | Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12242332, PubMed:16606821, PubMed:32322062). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:17428920, PubMed:26160948, PubMed:32322062). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase RNF139 (PubMed:16606821, PubMed:22143767). {ECO:0000269|PubMed:12242332, ECO:0000269|PubMed:16606821, ECO:0000269|PubMed:17428920, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:26160948, ECO:0000269|PubMed:32322062}. |
| Q9Y5Y4 | PTGDR2 | S338 | ochoa | Prostaglandin D2 receptor 2 (Chemoattractant receptor-homologous molecule expressed on Th2 cells) (G-protein coupled receptor 44) (CD antigen CD294) | Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses. {ECO:0000269|PubMed:11208866, ECO:0000269|PubMed:11535533, ECO:0000269|PubMed:17196174}. |
| Q9Y6D9 | MAD1L1 | S29 | psp | Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) | Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. |
| Q9Y6D9 | MAD1L1 | S417 | ochoa | Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) | Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. |
| Q9Y6J0 | CABIN1 | S20 | ochoa | Calcineurin-binding protein cabin-1 (Calcineurin inhibitor) (CAIN) | May be required for replication-independent chromatin assembly. May serve as a negative regulator of T-cell receptor (TCR) signaling via inhibition of calcineurin. Inhibition of activated calcineurin is dependent on both PKC and calcium signals. Acts as a negative regulator of p53/TP53 by keeping p53 in an inactive state on chromatin at promoters of a subset of it's target genes. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:9655484}. |
| Q9Y6N7 | ROBO1 | S1149 | ochoa | Roundabout homolog 1 (Deleted in U twenty twenty) (H-Robo-1) | Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). May be required for lung development (By similarity). {ECO:0000250|UniProtKB:O89026, ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:24560577, ECO:0000269|PubMed:26529257, ECO:0000305}. |
| Q9Y6Q2 | STON1 | S244 | ochoa | Stonin-1 (Stoned B-like factor) | May be involved in the endocytic machinery. {ECO:0000250}. |
| Q9Y6R1 | SLC4A4 | S219 | ochoa | Electrogenic sodium bicarbonate cotransporter 1 (Sodium bicarbonate cotransporter) (Na(+)/HCO3(-) cotransporter) (Solute carrier family 4 member 4) (kNBC1) | Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH. {ECO:0000269|PubMed:10069984, ECO:0000269|PubMed:11744745, ECO:0000269|PubMed:12411514, ECO:0000269|PubMed:12730338, ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:14567693, ECO:0000269|PubMed:15218065, ECO:0000269|PubMed:15713912, ECO:0000269|PubMed:15817634, ECO:0000269|PubMed:15930088, ECO:0000269|PubMed:16636648, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:17661077, ECO:0000269|PubMed:23324180, ECO:0000269|PubMed:23636456, ECO:0000269|PubMed:29500354, ECO:0000269|PubMed:9235899, ECO:0000269|PubMed:9651366}. |
| Q9Y6X8 | ZHX2 | S625 | ochoa | Zinc fingers and homeoboxes protein 2 (Alpha-fetoprotein regulator 1) (AFP regulator 1) (Regulator of AFP) (Zinc finger and homeodomain protein 2) | Acts as a transcriptional repressor (PubMed:12741956). Represses the promoter activity of the CDC25C gene stimulated by NFYA (PubMed:12741956). May play a role in retinal development where it regulates the composition of bipolar cell populations, by promoting differentiation of bipolar OFF-type cells (By similarity). In the brain, may promote maintenance and suppress differentiation of neural progenitor cells in the developing cortex (By similarity). {ECO:0000250|UniProtKB:Q8C0C0, ECO:0000269|PubMed:12741956}. |
| S4R3N1 | HSPE1-MOB4 | S53 | ochoa | 10 kDa heat shock protein, mitochondrial (10 kDa chaperonin) (Chaperonin 10) (MOB-like protein phocein) (Mob1 homolog 3) (Mps one binder kinase activator-like 3) (Preimplantation protein 3) | Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein. {ECO:0000256|ARBA:ARBA00046093}.; FUNCTION: Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation. {ECO:0000256|ARBA:ARBA00044741}. |
| V9GYQ6 | None | S70 | ochoa | Uncharacterized protein | None |
| P17987 | TCP1 | S374 | Sugiyama | T-complex protein 1 subunit alpha (TCP-1-alpha) (EC 3.6.1.-) (CCT-alpha) (Chaperonin containing T-complex polypeptide 1 subunit 1) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P60174 | TPI1 | S212 | Sugiyama | Triosephosphate isomerase (TIM) (EC 5.3.1.1) (Methylglyoxal synthase) (EC 4.2.3.3) (Triose-phosphate isomerase) | Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis. {ECO:0000269|PubMed:18562316}.; FUNCTION: It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids. {ECO:0000250|UniProtKB:P00939}. |
| Q9HAW4 | CLSPN | S265 | EPSD|PSP | Claspin (hClaspin) | Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| P61247 | RPS3A | S192 | Sugiyama | Small ribosomal subunit protein eS1 (40S ribosomal protein S3a) (v-fos transformation effector protein) (Fte-1) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). May play a role during erythropoiesis through regulation of transcription factor DDIT3 (By similarity). {ECO:0000255|HAMAP-Rule:MF_03122, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P37108 | SRP14 | S25 | Sugiyama | Signal recognition particle 14 kDa protein (SRP14) (18 kDa Alu RNA-binding protein) | Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (PubMed:11089964). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP (PubMed:11089964). The complex of SRP9 and SRP14 is required for SRP RNA binding (PubMed:11089964). {ECO:0000269|PubMed:11089964}. |
| P49588 | AARS1 | S627 | Sugiyama | Alanine--tRNA ligase, cytoplasmic (EC 6.1.1.7) (Alanyl-tRNA synthetase) (AlaRS) (Protein lactyltransferase AARS1) (EC 6.-.-.-) (Renal carcinoma antigen NY-REN-42) | Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:33909043). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:29273753). In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as TEAD1, TP53/p53 and YAP1 (PubMed:38512451, PubMed:38653238). Protein lactylation takes place in a two-step reaction: lactate is first activated by ATP to form lactate-AMP and then transferred to lysine residues of target proteins (PubMed:38512451, PubMed:38653238, PubMed:39322678). Acts as an inhibitor of TP53/p53 activity by catalyzing lactylation of TP53/p53 (PubMed:38653238). Acts as a positive regulator of the Hippo pathway by mediating lactylation of TEAD1 and YAP1 (PubMed:38512451). {ECO:0000269|PubMed:27622773, ECO:0000269|PubMed:27911835, ECO:0000269|PubMed:28493438, ECO:0000269|PubMed:29273753, ECO:0000269|PubMed:33909043, ECO:0000269|PubMed:38512451, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678}. |
| O00506 | STK25 | S30 | Sugiyama | Serine/threonine-protein kinase 25 (EC 2.7.11.1) (Ste20-like kinase) (Sterile 20/oxidant stress-response kinase 1) (SOK-1) (Ste20/oxidant stress response kinase 1) | Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:15037601, ECO:0000269|PubMed:18782753}. |
| P06733 | ENO1 | S349 | Sugiyama | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P06733 | ENO1 | S353 | Sugiyama | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P25205 | MCM3 | S34 | Sugiyama | DNA replication licensing factor MCM3 (EC 3.6.4.12) (DNA polymerase alpha holoenzyme-associated protein P1) (P1-MCM3) (RLF subunit beta) (p102) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (Probable). {ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000305|PubMed:35585232}. |
| P57723 | PCBP4 | S31 | Sugiyama | Poly(rC)-binding protein 4 (Alpha-CP4) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. {ECO:0000250}. |
| Q14683 | SMC1A | S514 | Sugiyama | Structural maintenance of chromosomes protein 1A (SMC protein 1A) (SMC-1-alpha) (SMC-1A) (Sb1.8) | Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint. {ECO:0000269|PubMed:11877377}. |
| Q15365 | PCBP1 | S27 | Sugiyama | Poly(rC)-binding protein 1 (Alpha-CP1) (Heterogeneous nuclear ribonucleoprotein E1) (hnRNP E1) (Nucleic acid-binding protein SUB2.3) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:15731341, PubMed:7556077, PubMed:7607214, PubMed:8152927). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:P60335, ECO:0000269|PubMed:15731341, ECO:0000269|PubMed:7556077, ECO:0000269|PubMed:7607214, ECO:0000269|PubMed:8152927}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD. {ECO:0000269|PubMed:12414943}. |
| Q9Y5L4 | TIMM13 | S57 | Sugiyama | Mitochondrial import inner membrane translocase subunit Tim13 | Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. {ECO:0000269|PubMed:11489896, ECO:0000269|PubMed:15254020}. |
| O00231 | PSMD11 | S298 | Sugiyama | 26S proteasome non-ATPase regulatory subunit 11 (26S proteasome regulatory subunit RPN6) (26S proteasome regulatory subunit S9) (26S proteasome regulatory subunit p44.5) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:22972301}. |
| O14757 | CHEK1 | S147 | Sugiyama | Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.; FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. {ECO:0000269|PubMed:22184239}. |
| P53350 | PLK1 | S529 | SIGNOR | Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13) | Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250|UniProtKB:P70032, ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080, ECO:0000269|PubMed:8991084}. |
| A8K0Z3 | WASHC1 | S105 | Sugiyama | WASH complex subunit 1 (CXYorf1-like protein on chromosome 9) (Protein FAM39E) (WAS protein family homolog 1) | Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:19922874, PubMed:19922875, PubMed:20498093, PubMed:23452853). Involved in endocytic trafficking of EGF (By similarity). Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration (PubMed:22114305). In T-cells involved in endosome-to-membrane recycling of receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T cell proliferation and effector function. In dendritic cells involved in endosome-to-membrane recycling of major histocompatibility complex (MHC) class II probably involving retromer and subsequently allowing antigen sampling, loading and presentation during T-cell activation (By similarity). Involved in Arp2/3 complex-dependent actin assembly driving Salmonella typhimurium invasion independent of ruffling. Involved in the exocytosis of MMP14 leading to matrix remodeling during invasive migration and implicating late endosome-to-plasma membrane tubular connections and cooperation with the exocyst complex (PubMed:24344185). Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity). {ECO:0000250|UniProtKB:C4AMC7, ECO:0000250|UniProtKB:Q8VDD8, ECO:0000269|PubMed:19922874, ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:20498093, ECO:0000269|PubMed:22114305, ECO:0000269|PubMed:23452853, ECO:0000305|PubMed:20498093}. |
| C4AMC7 | WASH3P | S105 | Sugiyama | Putative WAS protein family homolog 3 (Protein FAM39DP) | Acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:18159949, PubMed:20175130). Involved in endocytic trafficking of EGF (PubMed:20175130). Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration (By similarity). In T-cells involved in endosome-to-membrane recycling of receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T cell proliferation and effector function. In dendritic cells involved in endosome-to-membrane recycling of major histocompatibility complex (MHC) class II probably involving retromer and subsequently allowing antigen sampling, loading and presentation during T-cell activation. Involved in Arp2/3 complex-dependent actin assembly driving Salmonella typhimurium invasion independent of ruffling (By similarity). Involved in the exocytosis of MMP14 leading to matrix remodeling during invasive migration and implicating late endosome-to-plasma membrane tubular connections and cooperation with the exocyst complex (By similarity). Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity). {ECO:0000250|UniProtKB:A8K0Z3, ECO:0000250|UniProtKB:Q8VDD8, ECO:0000269|PubMed:18159949, ECO:0000269|PubMed:20175130}. |
| O14920 | IKBKB | S634 | Sugiyama | Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK-2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:9346484}. |
| O43765 | SGTA | S197 | Sugiyama | Small glutamine-rich tetratricopeptide repeat-containing protein alpha (Alpha-SGT) (Vpu-binding protein) (UBP) | Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails (PubMed:28104892). Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module (PubMed:28104892). Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins (PubMed:25535373, PubMed:28104892). It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states (PubMed:23129660, PubMed:25179605). Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex (PubMed:27193484). Binds directly to HSC70 and HSP70 and regulates their ATPase activity (PubMed:18759457). {ECO:0000269|PubMed:18759457, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; FUNCTION: (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection via interaction with DNAJB12, DNAJB14 and HSPA8/Hsc70 (PubMed:24675744). {ECO:0000269|PubMed:24675744}. |
| P02786 | TFRC | S620 | Sugiyama | Transferrin receptor protein 1 (TR) (TfR) (TfR1) (Trfr) (T9) (p90) (CD antigen CD71) [Cleaved into: Transferrin receptor protein 1, serum form (sTfR)] | Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity). {ECO:0000250|UniProtKB:Q62351, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus. {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.; FUNCTION: (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762, ECO:0000269|PubMed:36779763}.; FUNCTION: (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762}. |
| P11047 | LAMC1 | S942 | Sugiyama | Laminin subunit gamma-1 (Laminin B2 chain) (Laminin-1 subunit gamma) (Laminin-10 subunit gamma) (Laminin-11 subunit gamma) (Laminin-2 subunit gamma) (Laminin-3 subunit gamma) (Laminin-4 subunit gamma) (Laminin-6 subunit gamma) (Laminin-7 subunit gamma) (Laminin-8 subunit gamma) (Laminin-9 subunit gamma) (S-laminin subunit gamma) (S-LAM gamma) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. |
| P16070 | CD44 | S71 | Sugiyama | CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44) | Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640). {ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:18757307, ECO:0000269|PubMed:19703720, ECO:0000269|PubMed:22726066, ECO:0000269|PubMed:23589287, ECO:0000269|PubMed:7528188}. |
| P23381 | WARS1 | S213 | Sugiyama | Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS] | Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp). {ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220}.; FUNCTION: [Isoform 1]: Has no angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}.; FUNCTION: [T2-TrpRS]: Possesses an angiostatic activity but has no aminoacylation activity (PubMed:11773625, PubMed:11773626, PubMed:14630953). Inhibits fluid shear stress-activated responses of endothelial cells (PubMed:14630953). Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression (PubMed:14630953). {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:14630953}.; FUNCTION: [Isoform 2]: Has an angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}. |
| P31153 | MAT2A | S247 | Sugiyama | S-adenosylmethionine synthase isoform type-2 (AdoMet synthase 2) (EC 2.5.1.6) (Methionine adenosyltransferase 2) (MAT 2) (Methionine adenosyltransferase II) (MAT-II) | Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate. {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:25075345}. |
| P52789 | HK2 | S893 | Sugiyama | Hexokinase-2 (EC 2.7.1.1) (Hexokinase type II) (HK II) (Hexokinase-B) (Muscle form hexokinase) | Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively) (PubMed:23185017, PubMed:26985301, PubMed:29298880). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:29298880). Plays a key role in maintaining the integrity of the outer mitochondrial membrane by preventing the release of apoptogenic molecules from the intermembrane space and subsequent apoptosis (PubMed:18350175). {ECO:0000269|PubMed:18350175, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:26985301, ECO:0000269|PubMed:29298880}. |
| P61916 | NPC2 | S29 | Sugiyama | NPC intracellular cholesterol transporter 2 (Epididymal secretory protein E1) (Human epididymis-specific protein 1) (He1) (Niemann-Pick disease type C2 protein) | Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:11125141, PubMed:15937921, PubMed:17018531, PubMed:18772377, PubMed:29580834). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (PubMed:17018531, PubMed:18772377, PubMed:27238017). May bind and mobilize cholesterol that is associated with membranes (PubMed:18823126). NPC2 binds cholesterol with a 1:1 stoichiometry (PubMed:17018531). Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol (PubMed:17018531). The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport (By similarity). {ECO:0000250|UniProtKB:Q9Z0J0, ECO:0000269|PubMed:11125141, ECO:0000269|PubMed:15937921, ECO:0000269|PubMed:17018531, ECO:0000269|PubMed:18772377, ECO:0000269|PubMed:18823126, ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:29580834}. |
| Q16881 | TXNRD1 | S329 | Sugiyama | Thioredoxin reductase 1, cytoplasmic (TR) (EC 1.8.1.9) (Gene associated with retinoic and interferon-induced mortality 12 protein) (GRIM-12) (Gene associated with retinoic and IFN-induced mortality 12 protein) (KM-102-derived reductase-like factor) (Peroxidase TXNRD1) (EC 1.11.1.2) (Thioredoxin reductase TR1) | Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form (PubMed:8577704). Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (Probable). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). {ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:8577704, ECO:0000305|PubMed:17512005}.; FUNCTION: [Isoform 1]: Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. {ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8577704}.; FUNCTION: [Isoform 4]: Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2. {ECO:0000269|PubMed:15199063}.; FUNCTION: [Isoform 5]: Enhances the transcriptional activity of the estrogen receptor ESR2 only (PubMed:15199063). Mediates cell death induced by a combination of interferon-beta and retinoic acid (PubMed:9774665). {ECO:0000269|PubMed:15199063, ECO:0000269|PubMed:9774665}. |
| Q6IBS0 | TWF2 | S140 | Sugiyama | Twinfilin-2 (A6-related protein) (hA6RP) (Protein tyrosine kinase 9-like) (Twinfilin-1-like protein) | Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles. May play a role in regulating the mature length of the middle and short rows of stereocilia (By similarity). {ECO:0000250}. |
| Q6VEQ5 | WASH2P | S105 | Sugiyama | WAS protein family homolog 2 (CXYorf1-like protein on chromosome 2) (Protein FAM39B) | Acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. Involved in endocytic trafficking of EGF. Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration. In T-cells involved in endosome-to-membrane recycling of receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T-cell proliferation and effector function. In dendritic cells involved in endosome-to-membrane recycling of major histocompatibility complex (MHC) class II probably involving retromer and subsequently allowing antigen sampling, loading and presentation during T-cell activation. Involved in Arp2/3 complex-dependent actin assembly driving Salmonella typhimurium invasion independent of ruffling. Involved in the exocytosis of MMP14 leading to matrix remodeling during invasive migration and implicating late endosome-to-plasma membrane tubular connections and cooperation with the exocyst complex. Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity). {ECO:0000250|UniProtKB:A8K0Z3, ECO:0000250|UniProtKB:C4AMC7, ECO:0000250|UniProtKB:Q8VDD8}. |
| Q7RTV0 | PHF5A | S53 | Sugiyama | PHD finger-like domain-containing protein 5A (PHD finger-like domain protein 5A) (Splicing factor 3B-associated 14 kDa protein) (SF3b14b) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, PubMed:28541300, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:12234937, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, PHF5A is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937, PubMed:27720643). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). Also involved in elongation by RNA polymerase II as part of the PAF1 complex (PAF1C) (By similarity). PAF1C is required for maintenance of embryonic stem cell (ESC) self-renewal and cellular reprogramming of stem cells (By similarity). Maintains pluripotency by recruiting and stabilizing PAF1C on pluripotency genes loci, and by regulating the expression of the pluripotency genes (By similarity). Regulates the deposition of elongation-associated histone modifications, including dimethylated histone H3 'Lys-79' (H3K79me2) and trimethylated histone H3 'Lys-36' (H3K36me3), on PAF1C targets, self-renewal and pluripotency genes (By similarity). Regulates RNA polymerase II promoter-proximal pause release of the PAF1C targets and self-renewal genes, and the levels of elongating ('Ser-2' phosphorylated) RNA polymerase II in their gene bodies (By similarity). Regulates muscle specification in adult stem cells by stabilizing PAF1C in chromatin to promote myogenic differentiation (By similarity). Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha (By similarity). {ECO:0000250|UniProtKB:P83870, ECO:0000250|UniProtKB:P83871, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:28541300, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| Q92621 | NUP205 | S1857 | Sugiyama | Nuclear pore complex protein Nup205 (205 kDa nucleoporin) (Nucleoporin Nup205) | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor NUP62 and other nucleoporins, but not NUP153 and TPR, to the NPC (PubMed:15229283). In association with TMEM209, may be involved in nuclear transport of various nuclear proteins in addition to MYC (PubMed:22719065). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22719065, ECO:0000269|PubMed:9348540}. |
| Q9BQS8 | FYCO1 | S659 | Sugiyama | FYVE and coiled-coil domain-containing protein 1 (Zinc finger FYVE domain-containing protein 7) | May mediate microtubule plus end-directed vesicle transport. {ECO:0000269|PubMed:20100911}. |
| Q9NQA3 | WASH6P | S87 | Sugiyama | WAS protein family homolog 6 (Protein FAM39A) | May act as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. {ECO:0000250|UniProtKB:A8K0Z3, ECO:0000250|UniProtKB:C4AMC7}. |
| O14965 | AURKA | S266 | GPS6|ELM|EPSD|PSP | Aurora kinase A (EC 2.7.11.1) (Aurora 2) (Aurora/IPL1-related kinase 1) (ARK-1) (Aurora-related kinase 1) (Breast tumor-amplified kinase) (Ipl1- and aurora-related kinase 1) (Serine/threonine-protein kinase 15) (Serine/threonine-protein kinase 6) (Serine/threonine-protein kinase Ayk1) (Serine/threonine-protein kinase aurora-A) | Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735). {ECO:0000250|UniProtKB:A0A8I3S724, ECO:0000269|PubMed:11039908, ECO:0000269|PubMed:11551964, ECO:0000269|PubMed:12390251, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:14523000, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15128871, ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:15987997, ECO:0000269|PubMed:17125279, ECO:0000269|PubMed:17360485, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19668197, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:27192185, ECO:0000269|PubMed:27335426, ECO:0000269|PubMed:28218735}. |
| P08195 | SLC3A2 | S518 | Sugiyama | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| P15880 | RPS2 | S206 | Sugiyama | Small ribosomal subunit protein uS5 (40S ribosomal protein S2) (40S ribosomal protein S4) (Protein LLRep3) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:23636399). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:23636399). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:23636399). Plays a role in the assembly and function of the 40S ribosomal subunit (By similarity). Mutations in this protein affects the control of translational fidelity (By similarity). Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly (By similarity). {ECO:0000250|UniProtKB:P25443, ECO:0000269|PubMed:23636399}. |
| O15264 | MAPK13 | S38 | Sugiyama | Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}. |
| O00488 | ZNF593 | S40 | Sugiyama | Zinc finger protein 593 (Zinc finger protein T86) | Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome (PubMed:32669547). Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity (PubMed:9115366). {ECO:0000269|PubMed:9115366, ECO:0000305|PubMed:32669547}. |
| P34897 | SHMT2 | S90 | Sugiyama | Serine hydroxymethyltransferase, mitochondrial (SHMT) (EC 2.1.2.1) (Glycine hydroxymethyltransferase) (Serine methylase) | Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:29452640, ECO:0000269|PubMed:33015733}. |
| P52597 | HNRNPF | S63 | Sugiyama | Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] | Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}. |
| P43034 | PAFAH1B1 | S157 | Sugiyama | Platelet-activating factor acetylhydrolase IB subunit beta (Lissencephaly-1 protein) (LIS-1) (PAF acetylhydrolase 45 kDa subunit) (PAF-AH 45 kDa subunit) (PAF-AH alpha) (PAFAH alpha) | Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity). {ECO:0000250|UniProtKB:P43033, ECO:0000250|UniProtKB:P63005, ECO:0000269|PubMed:15173193, ECO:0000269|PubMed:22956769}. |
| O75369 | FLNB | S1442 | Sugiyama | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75582 | RPS6KA5 | S436 | Sugiyama | Ribosomal protein S6 kinase alpha-5 (S6K-alpha-5) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 5) (Nuclear mitogen- and stress-activated protein kinase 1) (RSK-like protein kinase) (RSKL) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:18511904, PubMed:9687510, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810). {ECO:0000250|UniProtKB:Q8C050, ECO:0000269|PubMed:11909979, ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904, ECO:0000269|PubMed:25851810, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}. |
| P33316 | DUT | S130 | Sugiyama | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase) | Catalyzes the cleavage of 2'-deoxyuridine 5'-triphosphate (dUTP) into 2'-deoxyuridine 5'-monophosphate (dUMP) and inorganic pyrophosphate and through its action efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo thymidylate biosynthesis (PubMed:17880943, PubMed:8631816, PubMed:8805593). Inhibits peroxisome proliferator-activated receptor (PPAR) activity by binding of its N-terminal to PPAR, preventing the latter's dimerization with retinoid X receptor (By similarity). Essential for embryonic development (By similarity). {ECO:0000250|UniProtKB:P70583, ECO:0000250|UniProtKB:Q9CQ43, ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593}. |
| O75676 | RPS6KA4 | S421 | Sugiyama | Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| Q12805 | EFEMP1 | S382 | Sugiyama | EGF-containing fibulin-like extracellular matrix protein 1 (Extracellular protein S1-5) (Fibrillin-like protein) (Fibulin-3) (FIBL-3) | Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulator of chondrocyte differentiation. In the olfactory epithelium, it may regulate glial cell migration, differentiation and the ability of glial cells to support neuronal neurite outgrowth. {ECO:0000269|PubMed:19804359, ECO:0000269|PubMed:19887559, ECO:0000269|PubMed:20005202}. |
| O43399 | TPD52L2 | S104 | Sugiyama | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| P40227 | CCT6A | S49 | Sugiyama | T-complex protein 1 subunit zeta (TCP-1-zeta) (EC 3.6.1.-) (Acute morphine dependence-related protein 2) (CCT-zeta-1) (Chaperonin containing T-complex polypeptide 1 subunit 6A) (HTR3) (Tcp20) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q9HAW4 | CLSPN | S1246 | PSP | Claspin (hClaspin) | Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| Q9UBR2 | CTSZ | S195 | Sugiyama | Cathepsin Z (EC 3.4.18.1) (Cathepsin P) (Cathepsin X) | Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity (PubMed:10504234). Capable of producing kinin potentiating peptides (By similarity). {ECO:0000250|UniProtKB:Q9R1T3, ECO:0000269|PubMed:10504234}. |
| Q14103 | HNRNPD | S271 | Sugiyama | Heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) (AU-rich element RNA-binding protein 1) | Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation. {ECO:0000269|PubMed:10080887, ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:24423872}. |
| P02786 | TFRC | S159 | Sugiyama | Transferrin receptor protein 1 (TR) (TfR) (TfR1) (Trfr) (T9) (p90) (CD antigen CD71) [Cleaved into: Transferrin receptor protein 1, serum form (sTfR)] | Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity). {ECO:0000250|UniProtKB:Q62351, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus. {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.; FUNCTION: (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762, ECO:0000269|PubMed:36779763}.; FUNCTION: (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762}. |
| P06493 | CDK1 | S178 | Sugiyama | Cyclin-dependent kinase 1 (CDK1) (EC 2.7.11.22) (EC 2.7.11.23) (Cell division control protein 2 homolog) (Cell division protein kinase 1) (p34 protein kinase) | Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30139873, PubMed:30704899). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LBR, MKI67, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RBBP8/CtIP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19202191, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25012651, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30704899, PubMed:32351706, PubMed:34741373). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:18480403, PubMed:20360007, PubMed:2188730, PubMed:2344612, PubMed:30139873). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007). Phosphorylates KRT5 during prometaphase and metaphase (By similarity). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown (PubMed:2188730, PubMed:2344612, PubMed:37788673). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706). Phosphorylates SKA3 on multiple sites during mitosis which promotes SKA3 binding to the NDC80 complex and anchoring of the SKA complex to kinetochores, to enable stable attachment of mitotic spindle microtubules to kinetochores (PubMed:28479321, PubMed:31804178, PubMed:32491969). {ECO:0000250|UniProtKB:P11440, ECO:0000250|UniProtKB:P39951, ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:25012651, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:28479321, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:30723163, ECO:0000269|PubMed:31804178, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32491969, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:37788673}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. {ECO:0000269|PubMed:21516087}. |
| P08631 | HCK | S78 | Sugiyama | Tyrosine-protein kinase HCK (EC 2.7.10.2) (Hematopoietic cell kinase) (Hemopoietic cell kinase) (p59-HCK/p60-HCK) (p59Hck) (p61Hck) | Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790, ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024, ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982, ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996, ECO:0000269|PubMed:9407116}. |
| O15357 | INPPL1 | S189 | Sugiyama | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (EC 3.1.3.86) (Inositol polyphosphate phosphatase-like protein 1) (INPPL-1) (Protein 51C) (SH2 domain-containing inositol 5'-phosphatase 2) (SH2 domain-containing inositol phosphatase 2) (SHIP-2) | Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:16824732). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:9660833). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (By similarity). Part of a signaling pathway that regulates actin cytoskeleton remodeling (PubMed:11739414, PubMed:12676785). Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation (PubMed:15668240). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading (PubMed:12235291). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (PubMed:15735664). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (PubMed:17135240). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (PubMed:12690104). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:11016922). Involved in EGF signaling pathway (PubMed:11349134). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (PubMed:11349134). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (PubMed:11349134). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (PubMed:23273569). {ECO:0000250|UniProtKB:F1PNY0, ECO:0000250|UniProtKB:Q6P549, ECO:0000250|UniProtKB:Q9WVR3, ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12676785, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15668240, ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:17135240, ECO:0000269|PubMed:21624956, ECO:0000269|PubMed:23273569, ECO:0000269|PubMed:9660833}. |
| P09769 | FGR | S418 | Sugiyama | Tyrosine-protein kinase Fgr (EC 2.7.10.2) (Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog) (Proto-oncogene c-Fgr) (p55-Fgr) (p58-Fgr) (p58c-Fgr) | Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as a negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as a positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity). {ECO:0000250|UniProtKB:P14234, ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}. |
| P11309 | PIM1 | S189 | Sugiyama | Serine/threonine-protein kinase pim-1 (EC 2.7.11.1) | Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15528381, PubMed:1825810, PubMed:31548394). Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3) (PubMed:18593906). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (By similarity). The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (By similarity). Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (By similarity). Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis (PubMed:19749799). Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (PubMed:16356754). Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability (PubMed:12431783). Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (PubMed:18593906). Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (PubMed:18593906). May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (PubMed:10664448). Also acts as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (By similarity). Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394). Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol (PubMed:37797010). Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (PubMed:18056989). Promotes brown adipocyte differentiation (By similarity). {ECO:0000250|UniProtKB:P06803, ECO:0000269|PubMed:10664448, ECO:0000269|PubMed:12431783, ECO:0000269|PubMed:15528381, ECO:0000269|PubMed:16356754, ECO:0000269|PubMed:18056989, ECO:0000269|PubMed:1825810, ECO:0000269|PubMed:18593906, ECO:0000269|PubMed:19749799, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:37797010}. |
| P47756 | CAPZB | S184 | Sugiyama | F-actin-capping protein subunit beta (CapZ beta) | F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:A9XFX6, ECO:0000269|PubMed:21834987}. |
| Q96I99 | SUCLG2 | S98 | Sugiyama | Succinate--CoA ligase [GDP-forming] subunit beta, mitochondrial (EC 6.2.1.4) (GTP-specific succinyl-CoA synthetase subunit beta) (G-SCS) (GTPSCS) (Succinyl-CoA synthetase beta-G chain) (SCS-betaG) | GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit. {ECO:0000255|HAMAP-Rule:MF_03221}. |
| P15735 | PHKG2 | S297 | Sugiyama | Phosphorylase b kinase gamma catalytic chain, liver/testis isoform (PHK-gamma-LT) (PHK-gamma-T) (EC 2.7.11.19) (PSK-C3) (Phosphorylase kinase subunit gamma-2) | Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM (PubMed:35549678). {ECO:0000250|UniProtKB:P31325, ECO:0000269|PubMed:10487978, ECO:0000269|PubMed:35549678}. |
| P16234 | PDGFRA | S601 | Sugiyama | Platelet-derived growth factor receptor alpha (PDGF-R-alpha) (PDGFR-alpha) (EC 2.7.10.1) (Alpha platelet-derived growth factor receptor) (Alpha-type platelet-derived growth factor receptor) (CD140 antigen-like family member A) (CD140a antigen) (Platelet-derived growth factor alpha receptor) (Platelet-derived growth factor receptor 2) (PDGFR-2) (CD antigen CD140a) | Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:10734113, ECO:0000269|PubMed:10947961, ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:1646396, ECO:0000269|PubMed:17087943, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17141222, ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664, ECO:0000269|PubMed:8760137, ECO:0000269|PubMed:8943348}. |
| P36888 | FLT3 | S618 | Sugiyama | Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135) | Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. {ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:16627759, ECO:0000269|PubMed:18490735, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21067588, ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:21516120, ECO:0000269|PubMed:7507245}. |
| P61221 | ABCE1 | S186 | Sugiyama | ATP-binding cassette sub-family E member 1 (EC 3.6.5.-) (2'-5'-oligoadenylate-binding protein) (HuHP68) (RNase L inhibitor) (Ribonuclease 4 inhibitor) (RNS4I) | Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly (PubMed:20122402, PubMed:21448132). Able to hydrolyze ATP, GTP, UTP and CTP (PubMed:20122402). Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits (PubMed:20122402, PubMed:21448132). Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota) (PubMed:20122402, PubMed:21448132). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132). Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA (PubMed:29861391). As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy (PubMed:29861391). RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) to RNASEL (PubMed:9660177). Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway (PubMed:11585831, PubMed:9660177, PubMed:9847332). {ECO:0000269|PubMed:11585831, ECO:0000269|PubMed:20122402, ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:29861391, ECO:0000269|PubMed:9660177, ECO:0000269|PubMed:9847332}.; FUNCTION: (Microbial infection) May act as a chaperone for post-translational events during HIV-1 capsid assembly. {ECO:0000269|PubMed:9847332}.; FUNCTION: (Microbial infection) Plays a role in the down-regulation of the 2-5A/RNASEL pathway during encephalomyocarditis virus (EMCV) and HIV-1 infections. {ECO:0000269|PubMed:9660177}. |
| P55060 | CSE1L | S377 | Sugiyama | Exportin-2 (Exp2) (Cellular apoptosis susceptibility protein) (Chromosome segregation 1-like protein) (Importin-alpha re-exporter) | Export receptor for importin-alpha. Mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates (cargos) have been released into the nucleoplasm. In the nucleus binds cooperatively to importin-alpha and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the importin-alpha from the export receptor. CSE1L/XPO2 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. {ECO:0000269|PubMed:9323134}. |
| Q92626 | PXDN | S1300 | Sugiyama | Peroxidasin homolog (EC 1.11.2.-) (Melanoma-associated antigen MG50) (Peroxidasin 1) (hsPxd01) (Vascular peroxidase 1) (p53-responsive gene 2 protein) [Cleaved into: PXDN active fragment] | Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncross-linked collagen IV/COL4A1 NC1 hexamer (PubMed:18929642, PubMed:19590037, PubMed:22842973, PubMed:25708780, PubMed:25713063, PubMed:27697841, PubMed:28154175, PubMed:34679700). In turns, directly contributes to the collagen IV network-dependent fibronectin/FN and laminin assembly, which is required for full extracellular matrix (ECM)-mediated signaling (PubMed:19590037, PubMed:32543734, PubMed:34679700). Thus, sulfilimine cross-links are essential for growth factor-induced cell proliferation and survival in endothelial cells, an event essential to basement membrane integrity (PubMed:32543734). In addition, through the bromide oxidation, may promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and FAK pathways (PubMed:25713063). Moreover brominates alpha2 collagen IV chain/COL4A2 at 'Tyr-1485' and leads to bromine enrichment of the basement membranes (PubMed:32571911). In vitro, can also catalyze the two-electron oxidation of thiocyanate and iodide and these two substrates could effectively compete with bromide and thus inhibit the formation of sulfilimine bonds (PubMed:28154175). Binds laminins (PubMed:32485152). May play a role in the organization of eyeball structure and lens development during eye development (By similarity). {ECO:0000250|UniProtKB:Q3UQ28, ECO:0000269|PubMed:18929642, ECO:0000269|PubMed:19590037, ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:25713063, ECO:0000269|PubMed:27697841, ECO:0000269|PubMed:28154175, ECO:0000269|PubMed:32485152, ECO:0000269|PubMed:32543734, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:34679700}. |
| P22612 | PRKACG | S54 | Sugiyama | cAMP-dependent protein kinase catalytic subunit gamma (PKA C-gamma) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus. |
| P00540 | MOS | S73 | SIGNOR | Proto-oncogene serine/threonine-protein kinase mos (EC 2.7.11.1) (Oocyte maturation factor mos) (Proto-oncogene c-Mos) | Serine/threonine kinase involved in the regulation of MAPK signaling. Is an activator of the ERK1/2 signaling cascade playing an essential role in the stimulation of oocyte maturation. {ECO:0000269|PubMed:34779126, ECO:0000269|PubMed:34997960, ECO:0000269|PubMed:35670744}. |
| Q12824 | SMARCB1 | S111 | Sugiyama | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (BRG1-associated factor 47) (BAF47) (Integrase interactor 1 protein) (SNF5 homolog) (hSNF5) | Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1. {ECO:0000250|UniProtKB:Q9Z0H3, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:12226744, ECO:0000269|PubMed:14604992, ECO:0000269|PubMed:16267391, ECO:0000269|PubMed:16314535, ECO:0000269|PubMed:9448295}. |
| Q01518 | CAP1 | S431 | Sugiyama | Adenylyl cyclase-associated protein 1 (CAP 1) | Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. |
| O75822 | EIF3J | S202 | Sugiyama | Eukaryotic translation initiation factor 3 subunit J (eIF3j) (Eukaryotic translation initiation factor 3 subunit 1) (eIF-3-alpha) (eIF3 p35) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| P23284 | PPIB | S150 | Sugiyama | Peptidyl-prolyl cis-trans isomerase B (PPIase B) (EC 5.2.1.8) (CYP-S1) (Cyclophilin B) (Rotamase B) (S-cyclophilin) (SCYLP) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. {ECO:0000269|PubMed:20676357}. |
| Q9HCN8 | SDF2L1 | S40 | Sugiyama | Stromal cell-derived factor 2-like protein 1 (SDF2-like protein 1) (PWP1-interacting protein 8) | None |
| Q9UBU9 | NXF1 | S223 | Sugiyama | Nuclear RNA export factor 1 (Tip-associated protein) (Tip-associating protein) (mRNA export factor TAP) | Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway) (PubMed:10924507). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex (PubMed:18364396, PubMed:19165146, PubMed:9660949). ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export (PubMed:18364396, PubMed:19165146, PubMed:9660949). Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). {ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:19165146, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:9660949}. |
| Q9Y4W2 | LAS1L | S636 | Sugiyama | Ribosomal biogenesis protein LAS1L (Endoribonuclease LAS1L) (EC 3.1.-.-) (Protein LAS1 homolog) | Required for the synthesis of the 60S ribosomal subunit and maturation of the 28S rRNA (PubMed:20647540). Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Required for the efficient pre-rRNA processing at both ends of internal transcribed spacer 2 (ITS2) (PubMed:22083961). {ECO:0000269|PubMed:20647540, ECO:0000269|PubMed:22083961, ECO:0000269|PubMed:22872859}. |
| P62829 | RPL23 | S115 | Sugiyama | Large ribosomal subunit protein uL14 (60S ribosomal protein L17) (60S ribosomal protein L23) | Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| P02533 | KRT14 | S435 | Sugiyama | Keratin, type I cytoskeletal 14 (Cytokeratin-14) (CK-14) (Keratin-14) (K14) | The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filaments in vitro. {ECO:0000269|PubMed:11724817}. |
| P15880 | RPS2 | S225 | Sugiyama | Small ribosomal subunit protein uS5 (40S ribosomal protein S2) (40S ribosomal protein S4) (Protein LLRep3) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:23636399). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:23636399). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:23636399). Plays a role in the assembly and function of the 40S ribosomal subunit (By similarity). Mutations in this protein affects the control of translational fidelity (By similarity). Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly (By similarity). {ECO:0000250|UniProtKB:P25443, ECO:0000269|PubMed:23636399}. |
| O95273 | CCNDBP1 | S313 | GPS6 | Cyclin-D1-binding protein 1 (Grap2 and cyclin-D-interacting protein) (Human homolog of Maid) | May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription. {ECO:0000269|PubMed:10801854}. |
| P42685 | FRK | S324 | Sugiyama | Tyrosine-protein kinase FRK (EC 2.7.10.2) (FYN-related kinase) (Nuclear tyrosine protein kinase RAK) (Protein-tyrosine kinase 5) | Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor. {ECO:0000269|PubMed:19345329}. |
| P13667 | PDIA4 | S154 | Sugiyama | Protein disulfide-isomerase A4 (EC 5.3.4.1) (Endoplasmic reticulum resident protein 70) (ER protein 70) (ERp70) (Endoplasmic reticulum resident protein 72) (ER protein 72) (ERp-72) (ERp72) | None |
| Q00610 | CLTC | S1127 | Sugiyama | Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| P35658 | NUP214 | S433 | Sugiyama | Nuclear pore complex protein Nup214 (214 kDa nucleoporin) (Nucleoporin Nup214) (Protein CAN) | Part of the nuclear pore complex (PubMed:9049309). Has a critical role in nucleocytoplasmic transport (PubMed:31178128). May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex (PubMed:31178128, PubMed:8108440). {ECO:0000269|PubMed:31178128, ECO:0000269|PubMed:9049309, ECO:0000303|PubMed:8108440}.; FUNCTION: (Microbial infection) Required for capsid disassembly of the human adenovirus 5 (HadV-5) leading to release of the viral genome to the nucleus (in vitro). {ECO:0000269|PubMed:25410864}. |
| Q15181 | PPA1 | S127 | Sugiyama | Inorganic pyrophosphatase (EC 3.6.1.1) (Pyrophosphate phospho-hydrolase) (PPase) | None |
| P48736 | PIK3CG | S496 | Sugiyama | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3-kinase subunit gamma) (PI3K-gamma) (PI3Kgamma) (PtdIns-3-kinase subunit gamma) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma) (PtdIns-3-kinase subunit p110-gamma) (p110gamma) (Phosphoinositide-3-kinase catalytic gamma polypeptide) (Serine/threonine protein kinase PIK3CG) (EC 2.7.11.1) (p120-PI3K) | Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity). {ECO:0000250|UniProtKB:Q9JHG7, ECO:0000269|PubMed:11277933, ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730, ECO:0000269|PubMed:16123124, ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:31554793, ECO:0000269|PubMed:33054089, ECO:0000269|PubMed:7624799}. |
| P07195 | LDHB | S70 | Sugiyama | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| O60563 | CCNT1 | S444 | Sugiyama | Cyclin-T1 (CycT1) (Cyclin-T) | Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:35393539}.; FUNCTION: (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. {ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10329126}. |
| P24752 | ACAT1 | S195 | Sugiyama | Acetyl-CoA acetyltransferase, mitochondrial (EC 2.3.1.9) (Acetoacetyl-CoA thiolase) (T2) | This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148, PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688, PubMed:7728148, PubMed:9744475). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a major role in ketone body metabolism (PubMed:1715688, PubMed:17371050, PubMed:7728148, PubMed:9744475). {ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. |
| P40227 | CCT6A | S455 | Sugiyama | T-complex protein 1 subunit zeta (TCP-1-zeta) (EC 3.6.1.-) (Acute morphine dependence-related protein 2) (CCT-zeta-1) (Chaperonin containing T-complex polypeptide 1 subunit 6A) (HTR3) (Tcp20) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P51957 | NEK4 | S481 | Sugiyama | Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) | Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}. |
| O95786 | RIGI | S654 | EPSD|PSP | Antiviral innate immune response receptor RIG-I (ATP-dependent RNA helicase DDX58) (EC 3.6.4.13) (DEAD box protein 58) (RIG-I-like receptor 1) (RLR-1) (RNA sensor RIG-I) (Retinoic acid-inducible gene 1 protein) (RIG-1) (Retinoic acid-inducible gene I protein) (RIG-I) | Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:15208624, PubMed:15708988, PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988). The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms (PubMed:28469175, PubMed:31006531). Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons (PubMed:28469175, PubMed:31006531). Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.74). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:24366338, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:31006531, ECO:0000269|PubMed:34935440, ECO:0000269|PubMed:35263596, ECO:0000269|PubMed:36793726, ECO:0000269|Ref.74, ECO:0000303|PubMed:21616437, ECO:0000303|PubMed:21884169}. |
| Q8NBJ7 | SUMF2 | S264 | Sugiyama | Inactive C-alpha-formylglycine-generating enzyme 2 (Paralog of formylglycine-generating enzyme) (pFGE) (Sulfatase-modifying factor 2) | Lacks formylglycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1. {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15708861, ECO:0000269|PubMed:15962010}. |
| P53778 | MAPK12 | S35 | Sugiyama | Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}. |
| A8MPP1 | DDX11L8 | S279 | Sugiyama | Putative ATP-dependent DNA helicase DDX11-like protein 8 (EC 5.6.2.-) (DEAD/H box protein 11-like 8) | Putative DNA helicase. {ECO:0000305}. |
| O00165 | HAX1 | S162 | Sugiyama | HCLS1-associated protein X-1 (HS1-associating protein X-1) (HAX-1) (HS1-binding protein 1) (HSP1BP-1) | Recruits the Arp2/3 complex to the cell cortex and regulates reorganization of the cortical actin cytoskeleton via its interaction with KCNC3 and the Arp2/3 complex (PubMed:26997484). Slows down the rate of inactivation of KCNC3 channels (PubMed:26997484). Promotes GNA13-mediated cell migration. Involved in the clathrin-mediated endocytosis pathway. May be involved in internalization of ABC transporters such as ABCB11. May inhibit CASP9 and CASP3. Promotes cell survival. May regulate intracellular calcium pools. {ECO:0000269|PubMed:15339924, ECO:0000269|PubMed:16857965, ECO:0000269|PubMed:17545607, ECO:0000269|PubMed:18319618, ECO:0000269|PubMed:18971376, ECO:0000269|PubMed:26997484, ECO:0000269|PubMed:9058808}. |
| Q96FC9 | DDX11 | S277 | Sugiyama | ATP-dependent DNA helicase DDX11 (EC 5.6.2.3) (CHL1-related protein 1) (hCHLR1) (DEAD/H-box protein 11) (DNA 5'-3' helicase DDX11) (Keratinocyte growth factor-regulated gene 2 protein) (KRG-2) | DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis (PubMed:10648783, PubMed:21854770, PubMed:23797032, PubMed:26089203, PubMed:26503245). Its double-stranded DNA helicase activity requires either a minimal 5'-single-stranded tail length of approximately 15 nt (flap substrates) or 10 nt length single-stranded gapped DNA substrates of a partial duplex DNA structure for helicase loading and translocation along DNA in a 5' to 3' direction (PubMed:10648783, PubMed:18499658, PubMed:22102414). The helicase activity is capable of displacing duplex regions up to 100 bp, which can be extended up to 500 bp by the replication protein A (RPA) or the cohesion CTF18-replication factor C (Ctf18-RFC) complex activities (PubMed:18499658). Also shows ATPase- and helicase activities on substrates that mimic key DNA intermediates of replication, repair and homologous recombination reactions, including forked duplex, anti-parallel G-quadruplex and three-stranded D-loop DNA molecules (PubMed:22102414, PubMed:26503245). Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage (PubMed:23797032). Recruited with TIMELESS factor upon DNA-replication stress response at DNA replication fork to preserve replication fork progression, and hence ensure DNA replication fidelity (PubMed:26503245). Also cooperates with TIMELESS factor during DNA replication to regulate proper sister chromatid cohesion and mitotic chromosome segregation (PubMed:17105772, PubMed:18499658, PubMed:20124417, PubMed:23116066, PubMed:23797032). Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner; and hence it may contribute in Okazaki fragment processing at DNA replication fork during lagging strand DNA synthesis (PubMed:18499658). Its ability to function at DNA replication fork is modulated by its binding to long non-coding RNA (lncRNA) cohesion regulator non-coding RNA DDX11-AS1/CONCR, which is able to increase both DDX11 ATPase activity and binding to DNA replicating regions (PubMed:27477908). Also plays a role in heterochromatin organization (PubMed:21854770). Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (PubMed:26089203). Plays a role in embryonic development and prevention of aneuploidy (By similarity). Involved in melanoma cell proliferation and survival (PubMed:23116066). Associates with chromatin at DNA replication fork regions (PubMed:27477908). Binds to single- and double-stranded DNAs (PubMed:18499658, PubMed:22102414, PubMed:9013641). {ECO:0000250|UniProtKB:Q6AXC6, ECO:0000269|PubMed:10648783, ECO:0000269|PubMed:17105772, ECO:0000269|PubMed:18499658, ECO:0000269|PubMed:20124417, ECO:0000269|PubMed:21854770, ECO:0000269|PubMed:22102414, ECO:0000269|PubMed:23116066, ECO:0000269|PubMed:23797032, ECO:0000269|PubMed:26089203, ECO:0000269|PubMed:26503245, ECO:0000269|PubMed:27477908}.; FUNCTION: (Microbial infection) Required for bovine papillomavirus type 1 regulatory protein E2 loading onto mitotic chromosomes during DNA replication for the viral genome to be maintained and segregated. {ECO:0000269|PubMed:17189189}. |
| P18848 | ATF4 | S184 | PSP | Cyclic AMP-dependent transcription factor ATF-4 (cAMP-dependent transcription factor ATF-4) (Activating transcription factor 4) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (Tax-responsive enhancer element-binding protein 67) (TaxREB67) | Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:16682973, PubMed:17684156, PubMed:31023583, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:31023583, PubMed:32132707). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:31023583, PubMed:32132706, PubMed:32132707). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Activates the expression of COX7A2L/SCAF1 downstream of the EIF2AK3/PERK-mediated unfolded protein response, thereby promoting formation of respiratory chain supercomplexes and increasing mitochondrial oxidative phosphorylation (PubMed:31023583). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988). May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (PubMed:33384352). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). {ECO:0000250|UniProtKB:Q06507, ECO:0000269|PubMed:11960987, ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17684156, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:26086088, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:31444471, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:33384352}.; FUNCTION: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. {ECO:0000269|PubMed:1847461}. |
| P52597 | HNRNPF | S279 | Sugiyama | Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] | Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}. |
| P55769 | SNU13 | S29 | Sugiyama | NHP2-like protein 1 (High mobility group-like nuclear protein 2 homolog 1) (OTK27) (SNU13 homolog) (hSNU13) (U4/U6.U5 small nuclear ribonucleoprotein SNU13) (U4/U6.U5 tri-snRNP 15.5 kDa protein) [Cleaved into: NHP2-like protein 1, N-terminally processed] | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28781166). Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly (PubMed:10545122, PubMed:17412961). The protein undergoes a conformational change upon RNA-binding (PubMed:10545122, PubMed:17412961, PubMed:28781166). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:39570315). {ECO:0000269|PubMed:10545122, ECO:0000269|PubMed:17412961, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| P43629 | KIR3DL1 | S296 | iPTMNet | Killer cell immunoglobulin-like receptor 3DL1 (CD158 antigen-like family member E) (HLA-BW4-specific inhibitory NK cell receptor) (Natural killer-associated transcript 3) (NKAT-3) (p70 natural killer cell receptor clones CL-2/CL-11) (p70 NK receptor CL-2/CL-11) (CD antigen CD158e) | Receptor on natural killer (NK) cells for HLA Bw4 allele. Inhibits the activity of NK cells thus preventing cell lysis. {ECO:0000269|PubMed:22020283}. |
| Q6XUX3 | DSTYK | S483 | Sugiyama | Dual serine/threonine and tyrosine protein kinase (EC 2.7.12.1) (Dusty protein kinase) (Dusty PK) (RIP-homologous kinase) (Receptor-interacting serine/threonine-protein kinase 5) (Sugen kinase 496) (SgK496) | Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}. |
| Q14141 | SEPTIN6 | S416 | Sugiyama | Septin-6 | Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Involved in cytokinesis. May play a role in HCV RNA replication. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). {ECO:0000269|PubMed:17229681, ECO:0000269|PubMed:17803907, ECO:0000305|PubMed:25588830}. |
| Q00536 | CDK16 | S336 | SIGNOR | Cyclin-dependent kinase 16 (EC 2.7.11.22) (Cell division protein kinase 16) (PCTAIRE-motif protein kinase 1) (Serine/threonine-protein kinase PCTAIRE-1) | Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}. |
| Q8NER1 | TRPV1 | S821 | SIGNOR|iPTMNet | Transient receptor potential cation channel subfamily V member 1 (TrpV1) (Capsaicin receptor) (Osm-9-like TRP channel 1) (OTRPC1) (Vanilloid receptor 1) | Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli (PubMed:11050376, PubMed:11243859, PubMed:11226139, PubMed:12077606). Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activated by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius (PubMed:37117175). Upon activation, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis. {ECO:0000250|UniProtKB:O35433, ECO:0000269|PubMed:11050376, ECO:0000269|PubMed:11226139, ECO:0000269|PubMed:11243859, ECO:0000269|PubMed:12077606, ECO:0000269|PubMed:37117175}. |
| Q12851 | MAP4K2 | S768 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
| Q9BT78 | COPS4 | S18 | Sugiyama | COP9 signalosome complex subunit 4 (SGN4) (Signalosome subunit 4) (JAB1-containing signalosome subunit 4) | Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:21102408, ECO:0000269|PubMed:9535219}. |
| Q5JTZ9 | AARS2 | S466 | Sugiyama | Alanine--tRNA ligase, mitochondrial (EC 6.1.1.7) (Alanyl-tRNA synthetase) (AlaRS) (Protein lactyltransferase AARS2) (EC 6.-.-.-) | Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:21549344). In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as CGAS (PubMed:39322678). Acts as an inhibitor of cGAS/STING signaling by catalyzing lactylation of CGAS, preventing the formation of liquid-like droplets in which CGAS is activated (PubMed:39322678). {ECO:0000269|PubMed:21549344, ECO:0000269|PubMed:39322678}. |
| Q9H5V8 | CDCP1 | S288 | Sugiyama | CUB domain-containing protein 1 (Membrane glycoprotein gp140) (Subtractive immunization M plus HEp3-associated 135 kDa protein) (SIMA135) (Transmembrane and associated with src kinases) (CD antigen CD318) | May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a novel marker for leukemia diagnosis and for immature hematopoietic stem cell subsets. Belongs to the tetraspanin web involved in tumor progression and metastasis. {ECO:0000269|PubMed:11466621, ECO:0000269|PubMed:12799299, ECO:0000269|PubMed:15153610, ECO:0000269|PubMed:16007225, ECO:0000269|PubMed:16404722, ECO:0000269|PubMed:8647901}. |
| Q13188 | STK3 | S37 | Sugiyama | Serine/threonine-protein kinase 3 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 2) (MST-2) (STE20-like kinase MST2) (Serine/threonine-protein kinase Krs-1) [Cleaved into: Serine/threonine-protein kinase 3 36kDa subunit (MST2/N); Serine/threonine-protein kinase 3 20kDa subunit (MST2/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation (PubMed:11278283, PubMed:8566796, PubMed:8816758). Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714, PubMed:29063833, PubMed:30622739). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714). STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250 (PubMed:21076410, PubMed:21723128). In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (PubMed:21104395). Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259' (PubMed:20212043). Phosphorylates MOBKL1A and RASSF2 (PubMed:19525978). Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 (PubMed:18328708, PubMed:18362890). {ECO:0000250|UniProtKB:Q9JI10, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:20212043, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:21723128, ECO:0000269|PubMed:23972470, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:8566796, ECO:0000269|PubMed:8816758}. |
| O75688 | PPM1B | S186 | Sugiyama | Protein phosphatase 1B (EC 3.1.3.16) (Protein phosphatase 2C isoform beta) (PP2C-beta) | Enzyme with a broad specificity. Dephosphorylates CDK2 and CDK6 in vitro. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser-172'. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:18930133, ECO:0000269|PubMed:22750291}. |
| P35813 | PPM1A | S181 | Sugiyama | Protein phosphatase 1A (EC 3.1.3.16) (Protein phosphatase 2C isoform alpha) (PP2C-alpha) (Protein phosphatase IA) | Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:18930133}. |
| Q8N0Z6 | TTC5 | S203 | SIGNOR | Tetratricopeptide repeat protein 5 (TPR repeat protein 5) (Stress-responsive activator of p300) (Protein Strap) | Cofactor involved in the regulation of various cellular mechanisms such as actin regulation, autophagy, chromatin regulation and DNA repair (PubMed:18451878, PubMed:31727855). In non-stress conditions, interacts with cofactor JMY in the cytoplasm which prevents JMY's actin nucleation activity and ability to activate the Arp2/3 complex. Acts as a negative regulator of nutrient stress-induced autophagy by preventing JMY's interaction with MAP1LC3B, thereby preventing autophagosome formation (By similarity). Involves in tubulin autoregulation by promoting its degradation in response to excess soluble tubulin (PubMed:31727855). To do so, associates with the active ribosome near the ribosome exit tunnel and with nascent tubulin polypeptides early during their translation, triggering tubulin mRNA-targeted degradation (PubMed:31727855). Following DNA damage, phosphorylated by DNA damage responsive protein kinases ATM and CHEK2, leading to its nuclear accumulation and stability. Nuclear TTC5/STRAP promotes the assembly of a stress-responsive p53/TP53 coactivator complex, which includes the coactivators JMY and p300, thereby increasing p53/TP53-dependent transcription and apoptosis. Also recruits arginine methyltransferase PRMT5 to p53/TP53 when DNA is damaged, allowing PRMT5 to methylate p53/TP53. In DNA stress conditions, also prevents p53/TP53 degradation by E3 ubiquitin ligase MDM2 (By similarity). Upon heat-shock stress, forms a chromatin-associated complex with heat-shock factor 1 HSF1 and p300/EP300 to stimulate heat-shock-responsive transcription, thereby increasing cell survival (PubMed:18451878). Mitochondrial TTC5/STRAP interacts with ATP synthase subunit beta ATP5F1B which decreased ATP synthase activity and lowers mitochondrial ATP production, thereby regulating cellular respiration and mitochondrial-dependent apoptosis. Mitochondrial TTC5/STRAP also regulates p53/TP53-mediated apoptosis (By similarity). {ECO:0000250|UniProtKB:Q99LG4, ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:31727855}. |
| Q8NEY1 | NAV1 | S377 | Sugiyama | Neuron navigator 1 (Pore membrane and/or filament-interacting-like protein 3) (Steerin-1) (Unc-53 homolog 1) (unc53H1) | May be involved in neuronal migration. {ECO:0000250}. |
| Q13557 | CAMK2D | S264 | Sugiyama | Calcium/calmodulin-dependent protein kinase type II subunit delta (CaM kinase II subunit delta) (CaMK-II subunit delta) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}. |
| P42167 | TMPO | S79 | Sugiyama | Lamina-associated polypeptide 2, isoforms beta/gamma (Thymopoietin, isoforms beta/gamma) (TP beta/gamma) (Thymopoietin-related peptide isoforms beta/gamma) (TPRP isoforms beta/gamma) [Cleaved into: Thymopoietin (TP) (Splenin); Thymopentin (TP5)] | May help direct the assembly of the nuclear lamina and thereby help maintain the structural organization of the nuclear envelope. Possible receptor for attachment of lamin filaments to the inner nuclear membrane. May be involved in the control of initiation of DNA replication through its interaction with NAKAP95.; FUNCTION: Thymopoietin (TP) and Thymopentin (TP5) may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide. |
| O43707 | ACTN4 | S796 | Sugiyama | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| Q92844 | TANK | S100 | SIGNOR | TRAF family member-associated NF-kappa-B activator (TRAF-interacting protein) (I-TRAF) | Adapter protein involved in I-kappa-B-kinase (IKK) regulation which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity. Acts as a regulator of TRAF function by maintaining them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. Negatively regulates NF-kappaB signaling and cell survival upon DNA damage (PubMed:25861989). Plays a role as an adapter to assemble ZC3H12A, USP10 in a deubiquitination complex which plays a negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Promotes UBP10-induced deubiquitination of TRAF6 in response to DNA damage (PubMed:25861989). May control negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2. {ECO:0000269|PubMed:12133833, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:25861989}. |
| Q15119 | PDK2 | S190 | Sugiyama | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 2) (PDH kinase 2) (PDKII) | Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis. {ECO:0000269|PubMed:17222789, ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:21283817, ECO:0000269|PubMed:22123926, ECO:0000269|PubMed:7499431, ECO:0000269|PubMed:9787110}. |
| Q15139 | PRKD1 | S460 | Sugiyama | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q15139 | PRKD1 | S68 | Sugiyama | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q14C86 | GAPVD1 | S746 | Sugiyama | GTPase-activating protein and VPS9 domain-containing protein 1 (GAPex-5) (Rab5-activating protein 6) | Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking. In the absence of insulin, it maintains RAB31 in an active state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles. Also involved in EGFR trafficking and degradation, possibly by promoting EGFR ubiquitination and subsequent degradation by the proteasome. Has GEF activity for Rab5 and GAP activity for Ras. {ECO:0000269|PubMed:16410077}. |
| Q15349 | RPS6KA2 | S634 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q15759 | MAPK11 | S32 | Sugiyama | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q15759 | MAPK11 | S37 | Sugiyama | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| P17980 | PSMC3 | S170 | Sugiyama | 26S proteasome regulatory subunit 6A (26S proteasome AAA-ATPase subunit RPT5) (Proteasome 26S subunit ATPase 3) (Proteasome subunit P50) (Tat-binding protein 1) (TBP-1) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC3 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798}. |
| Q16512 | PKN1 | S156 | Sugiyama | Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) | PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. |
| Q16513 | PKN2 | S183 | Sugiyama | Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2) | PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936, ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}. |
| P24666 | ACP1 | S119 | Sugiyama | Low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) (LMW-PTPase) (EC 3.1.3.48) (Adipocyte acid phosphatase) (Low molecular weight cytosolic acid phosphatase) (EC 3.1.3.2) (Red cell acid phosphatase 1) | Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates with differences in substrate specificity between isoform 1 and isoform 2. {ECO:0000269|PubMed:10336608, ECO:0000269|PubMed:9705307}.; FUNCTION: [Isoform 3]: Does not possess phosphatase activity. {ECO:0000269|PubMed:10336608}. |
| Q59H18 | TNNI3K | S424 | Sugiyama | Serine/threonine-protein kinase TNNI3K (EC 2.7.11.1) (Cardiac ankyrin repeat kinase) (Cardiac troponin I-interacting kinase) (TNNI3-interacting kinase) | May play a role in cardiac physiology. {ECO:0000303|PubMed:12721663}. |
| P06733 | ENO1 | S104 | Sugiyama | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P50502 | ST13 | S218 | Sugiyama | Hsc70-interacting protein (Hip) (Aging-associated protein 2) (Progesterone receptor-associated p48 protein) (Protein FAM10A1) (Putative tumor suppressor ST13) (Renal carcinoma antigen NY-REN-33) (Suppression of tumorigenicity 13 protein) | One HIP oligomer binds the ATPase domains of at least two HSC70 molecules dependent on activation of the HSC70 ATPase by HSP40. Stabilizes the ADP state of HSC70 that has a high affinity for substrate protein. Through its own chaperone activity, it may contribute to the interaction of HSC70 with various target proteins (By similarity). {ECO:0000250}. |
| Q6P0Q8 | MAST2 | S775 | Sugiyama | Microtubule-associated serine/threonine-protein kinase 2 (EC 2.7.11.1) | Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins. Functions in a multi-protein complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation (By similarity). {ECO:0000250}. |
| P06756 | ITGAV | S127 | Sugiyama | Integrin alpha-V (Vitronectin receptor) (Vitronectin receptor subunit alpha) (CD antigen CD51) [Cleaved into: Integrin alpha-V heavy chain; Integrin alpha-V light chain] | The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 and ITGAV:ITGB6 act as receptors for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, PubMed:28117447). ITGAV:ITGB3 acts as a receptor for CD40LG (PubMed:31331973). ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP (PubMed:10640428). {ECO:0000269|PubMed:10640428, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:28873464, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for Adenovirus type C. {ECO:0000269|PubMed:20615244}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1. {ECO:0000269|PubMed:15194773, ECO:0000269|PubMed:7519807, ECO:0000269|PubMed:9426447}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8. {ECO:0000269|PubMed:18045938}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1. {ECO:0000269|PubMed:24367260}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Human parechovirus 1. {ECO:0000269|PubMed:11160695}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus. {ECO:0000269|PubMed:23658209}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}. |
| O60831 | PRAF2 | S19 | Sugiyama | PRA1 family protein 2 | May be involved in ER/Golgi transport and vesicular traffic. Plays a proapoptotic role in cerulenin-induced neuroblastoma apoptosis. {ECO:0000269|PubMed:17975142, ECO:0000269|PubMed:18395978}. |
| Q04721 | NOTCH2 | S1621 | Sugiyama | Neurogenic locus notch homolog protein 2 (Notch 2) (hN2) [Cleaved into: Notch 2 extracellular truncation (N2ECD); Notch 2 intracellular domain (N2ICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus (PubMed:21378985, PubMed:21378989). Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737). {ECO:0000250|UniProtKB:O35516, ECO:0000269|PubMed:21378985, ECO:0000269|PubMed:21378989, ECO:0000269|PubMed:25985737, ECO:0000269|PubMed:29149593}. |
| Q12931 | TRAP1 | S361 | Sugiyama | Heat shock protein 75 kDa, mitochondrial (HSP 75) (Heat shock protein family C member 5) (TNFR-associated protein 1) (Tumor necrosis factor type 1 receptor-associated protein) (TRAP-1) | Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. {ECO:0000269|PubMed:23525905, ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:23747254}. |
| Q96S59 | RANBP9 | S613 | Sugiyama | Ran-binding protein 9 (RanBP9) (BPM-L) (BPM90) (Ran-binding protein M) (RanBPM) (RanBP7) | May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Acts as a mediator of cell spreading and actin cytoskeleton rearrangement (PubMed:18710924). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). May be involved in signaling of ITGB2/LFA-1 and other integrins (PubMed:14722085). Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway (PubMed:12147692). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation (PubMed:12361945, PubMed:18222118). Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity (PubMed:15558019). Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA. {ECO:0000269|PubMed:12147692, ECO:0000269|PubMed:12361945, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14722085, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15558019, ECO:0000269|PubMed:18222118, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972, ECO:0000305}. |
| P62913 | RPL11 | S51 | Sugiyama | Large ribosomal subunit protein uL5 (60S ribosomal protein L11) (CLL-associated antigen KW-12) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:19191325, PubMed:32669547). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:19191325, PubMed:32669547). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:19191325, PubMed:32669547). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:19191325, PubMed:32669547). As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:12962325, PubMed:19061985, PubMed:24120868). It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:24120868). Promotes nucleolar location of PML (By similarity). {ECO:0000250|UniProtKB:Q9CXW4, ECO:0000269|PubMed:12962325, ECO:0000269|PubMed:19061985, ECO:0000269|PubMed:19191325, ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:32669547}. |
| Q8IW41 | MAPKAPK5 | S206 | Sugiyama | MAP kinase-activated protein kinase 5 (MAPK-activated protein kinase 5) (MAPKAP kinase 5) (MAPKAP-K5) (MAPKAPK-5) (MK-5) (MK5) (EC 2.7.11.1) (p38-regulated/activated protein kinase) (PRAK) | Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}. |
| Q99426 | TBCB | S76 | Sugiyama | Tubulin-folding cofactor B (Cytoskeleton-associated protein 1) (Cytoskeleton-associated protein CKAPI) (Tubulin-specific chaperone B) | Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer (PubMed:9265649). Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth (By similarity). {ECO:0000250|UniProtKB:Q9D1E6, ECO:0000269|PubMed:9265649}. |
| Q8NBP7 | PCSK9 | S666 | GPS6 | Proprotein convertase subtilisin/kexin type 9 (EC 3.4.21.-) (Neural apoptosis-regulated convertase 1) (NARC-1) (Proprotein convertase 9) (PC9) (Subtilisin/kexin-like protease PC9) | Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments (PubMed:18039658). Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation (PubMed:17461796, PubMed:18197702, PubMed:18799458, PubMed:22074827). Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway (PubMed:18660751). Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways. {ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:18039658, ECO:0000269|PubMed:18197702, ECO:0000269|PubMed:18660751, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22074827, ECO:0000269|PubMed:22493497, ECO:0000269|PubMed:22580899}. |
| O14980 | XPO1 | S690 | Sugiyama | Exportin-1 (Exp1) (Chromosome region maintenance 1 protein homolog) | Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. {ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:20921223, ECO:0000269|PubMed:9311922, ECO:0000269|PubMed:9323133}.; FUNCTION: (Microbial infection) Mediates the export of unspliced or incompletely spliced RNAs out of the nucleus from different viruses including HIV-1, HTLV-1 and influenza A. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization. {ECO:0000269|PubMed:14612415, ECO:0000269|PubMed:9837918}. |
| P17706 | PTPN2 | S72 | Sugiyama | Tyrosine-protein phosphatase non-receptor type 2 (EC 3.1.3.48) (T-cell protein-tyrosine phosphatase) (TCPTP) | Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Also plays an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA. {ECO:0000269|PubMed:10734133, ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12138178, ECO:0000269|PubMed:12612081, ECO:0000269|PubMed:14966296, ECO:0000269|PubMed:15592458, ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:9488479}. |
| P22314 | UBA1 | S460 | Sugiyama | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
| P30038 | ALDH4A1 | S513 | Sugiyama | Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial (P5C dehydrogenase) (EC 1.2.1.88) (Aldehyde dehydrogenase family 4 member A1) (L-glutamate gamma-semialdehyde dehydrogenase) | Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes. {ECO:0000269|PubMed:22516612}. |
| P31327 | CPS1 | S597 | Sugiyama | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| Q13011 | ECH1 | S240 | Sugiyama | Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (EC 5.3.3.-) | Isomerization of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA. {ECO:0000250|UniProtKB:Q62651}. |
| Q14204 | DYNC1H1 | S3920 | Sugiyama | Cytoplasmic dynein 1 heavy chain 1 (Cytoplasmic dynein heavy chain 1) (Dynein heavy chain, cytosolic) | Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074). {ECO:0000269|PubMed:27462074}. |
| Q5T4S7 | UBR4 | S1723 | Sugiyama | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| Q6EMK4 | VASN | S487 | Sugiyama | Vasorin (Protein slit-like 2) | May act as an inhibitor of TGF-beta signaling. {ECO:0000269|PubMed:15247411}. |
| Q8IY84 | NIM1K | S82 | Sugiyama | Serine/threonine-protein kinase NIM1 (EC 2.7.11.1) (NIM1 serine/threonine-protein kinase) | None |
| Q96CU9 | FOXRED1 | S357 | Sugiyama | FAD-dependent oxidoreductase domain-containing protein 1 (EC 1.-.-.-) | Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599, PubMed:25678554). Involved in mid-late stages of complex I assembly (PubMed:25678554). {ECO:0000269|PubMed:20858599, ECO:0000269|PubMed:25678554}. |
| Q5JSH3 | WDR44 | S667 | Sugiyama | WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) | Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| Q8NE63 | HIPK4 | S298 | Sugiyama | Homeodomain-interacting protein kinase 4 (EC 2.7.11.1) | Protein kinase that phosphorylates human TP53 at Ser-9, and thus induces TP53 repression of BIRC5 promoter (By similarity). May act as a corepressor of transcription factors (Potential). {ECO:0000250, ECO:0000305}. |
| Q8TD08 | MAPK15 | S259 | Sugiyama | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| Q6ZRY4 | RBPMS2 | S60 | Sugiyama | RNA-binding protein with multiple splicing 2 (RNA binding protein, mRNA processing factor 2) | RNA-binding protein involved in the regulation of smooth muscle cell differentiation and proliferation in the gastrointestinal system (PubMed:25064856). Binds NOG mRNA, the major inhibitor of the bone morphogenetic protein (BMP) pathway. Mediates an increase of NOG mRNA levels, thereby contributing to the negative regulation of BMP signaling pathway and promoting reversible dedifferentiation and proliferation of smooth muscle cells (By similarity). Acts as a pre-mRNA alternative splicing regulator (By similarity). Mediates ACTN1 and FLNB alternative splicing (By similarity). Likely binds to mRNA tandem CAC trinucleotide or CA dinucleotide motifs (PubMed:24860013). {ECO:0000250|UniProtKB:B5DFF2, ECO:0000250|UniProtKB:Q9W6I1, ECO:0000269|PubMed:24860013, ECO:0000269|PubMed:25064856}. |
| Q7Z401 | DENND4A | S190 | Sugiyama | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q93062 | RBPMS | S53 | Sugiyama | RNA-binding protein with multiple splicing (RBP-MS) (RBPMS) (Heart and RRM expressed sequence) (Hermes) | [Isoform A]: RNA binding protein that mediates the regulation of pre-mRNA alternative splicing (AS) (PubMed:24860013, PubMed:26347403). Acts either as activator (FLNB, HSPG2, LIPA1, MYOCD, PTPRF and PPFIBP1) or repressor (TPM1, ACTN1, ITGA7, PIEZO1, LSM14B, MBNL1 and MBML2) of splicing events on specific pre-mRNA targets (By similarity). Together with RNA binding proteins RBFOX2 and MBNL1/2, activates a splicing program associated with differentiated contractile vascular smooth muscle cells (SMC) by regulating AS of numerous pre-mRNA involved in actin cytoskeleton and focal adhesion machineries, suggesting a role in promoting a cell differentiated state (By similarity). Binds to introns, exons and 3'-UTR associated with tandem CAC trinucleotide motifs separated by a variable spacer region, at a minimum as a dimer. The minimal length of RNA required for RBPMS-binding tandem CAC motifs is 15 nt, with spacing ranging from 1 to 9 nt. Can also bind to CA dinucleotide repeats (PubMed:24860013, PubMed:26347403). Mediates repression of TPM1 exon 3 by binding to CAC tandem repeats in the flanking intronic regions, followed by higher-order oligomerization and heterotypic interactions with other splicing regulators including MBNL1 and RBFOX2, which prevents assembly of ATP-dependent splicing complexes (By similarity). {ECO:0000250|UniProtKB:A0A8I6G705, ECO:0000269|PubMed:24860013, ECO:0000269|PubMed:26347403}.; FUNCTION: [Isoform C]: Acts as a regulator of pre-mRNA alternative splicing (AS) (By similarity). Binds mRNA (PubMed:17099224). Regulates AS of ACTN1, FLNB, although with lower efficiency than isoform A / RBPMSA (By similarity). Acts as coactivator of SMAD transcriptional activity in a TGFB1-dependent manner, possibly through increased phosphorylation of SMAD2 and SMAD3 at the C-terminal SSXS regions and promotion of the nuclear accumulation of SMAD proteins (PubMed:17099224). {ECO:0000250|UniProtKB:A0A8I6G705, ECO:0000269|PubMed:17099224}. |
| Q96RG2 | PASK | S996 | Sugiyama | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q9H093 | NUAK2 | S590 | Sugiyama | NUAK family SNF1-like kinase 2 (EC 2.7.11.1) (Omphalocele kinase 2) (SNF1/AMP kinase-related kinase) (SNARK) | Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958). {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:32845958}. |
| P05388 | RPLP0 | S37 | Sugiyama | Large ribosomal subunit protein uL10 (60S acidic ribosomal protein P0) (60S ribosomal protein L10E) | Ribosomal protein P0 is the functional equivalent of E.coli protein L10. |
| P49005 | POLD2 | S75 | Sugiyama | DNA polymerase delta subunit 2 (DNA polymerase delta subunit p50) | Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, PubMed:24449906). As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:12403614, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex (PubMed:24449906). Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7 (PubMed:24449906). {ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906}. |
| Q8NHW5 | RPLP0P6 | S37 | Sugiyama | Putative ribosomal protein uL10-like (60S acidic ribosomal protein P0-like) (Large ribosomal subunit protein uL10-like) | Ribosomal protein P0 is the functional equivalent of E.coli protein L10. {ECO:0000250}. |
| Q96AE4 | FUBP1 | S270 | Sugiyama | Far upstream element-binding protein 1 (FBP) (FUSE-binding protein 1) (DNA helicase V) (hDH V) | Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription. {ECO:0000269|PubMed:8125259}. |
| Q9Y5S2 | CDC42BPB | S221 | Sugiyama | Serine/threonine-protein kinase MRCK beta (EC 2.7.11.1) (CDC42-binding protein kinase beta) (CDC42BP-beta) (DMPK-like beta) (Myotonic dystrophy kinase-related CDC42-binding kinase beta) (MRCK beta) (Myotonic dystrophy protein kinase-like beta) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949762}. |
| Q9H2X6 | HIPK2 | S46 | Sugiyama | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| Q16595 | FXN | S89 | Sugiyama | Frataxin, mitochondrial (EC 1.16.3.1) (Friedreich ataxia protein) (Fxn) [Cleaved into: Frataxin intermediate form (i-FXN); Frataxin(56-210) (m56-FXN); Frataxin(78-210) (d-FXN) (m78-FXN); Frataxin mature form (Frataxin(81-210)) (m81-FXN); Extramitochondrial frataxin] | [Frataxin mature form]: Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:12785837, PubMed:24971490). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:24971490). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (PubMed:29576242). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity (PubMed:15641778). May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems (PubMed:11823441, PubMed:12755598). May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation (PubMed:15247478). May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (PubMed:15123683, PubMed:16239244). {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000269|PubMed:11823441, ECO:0000269|PubMed:12755598, ECO:0000269|PubMed:12785837, ECO:0000269|PubMed:15123683, ECO:0000269|PubMed:15247478, ECO:0000269|PubMed:15641778, ECO:0000269|PubMed:16239244, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:29576242}.; FUNCTION: [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1 (PubMed:20053667). May be involved in the cytoplasmic iron-sulfur protein biogenesis (PubMed:16091420). May contribute to oxidative stress resistance and overall cell survival (PubMed:16608849). {ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}. |
| Q9H4B4 | PLK3 | S86 | Sugiyama | Serine/threonine-protein kinase PLK3 (EC 2.7.11.21) (Cytokine-inducible serine/threonine-protein kinase) (FGF-inducible kinase) (Polo-like kinase 3) (PLK-3) (Proliferation-related kinase) | Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1. {ECO:0000269|PubMed:10557092, ECO:0000269|PubMed:11156373, ECO:0000269|PubMed:11447225, ECO:0000269|PubMed:11551930, ECO:0000269|PubMed:11971976, ECO:0000269|PubMed:12242661, ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:14980500, ECO:0000269|PubMed:15021912, ECO:0000269|PubMed:16478733, ECO:0000269|PubMed:16481012, ECO:0000269|PubMed:17264206, ECO:0000269|PubMed:17804415, ECO:0000269|PubMed:18062778, ECO:0000269|PubMed:18650425, ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:19490146, ECO:0000269|PubMed:20889502, ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:20951827, ECO:0000269|PubMed:21098032, ECO:0000269|PubMed:21264284, ECO:0000269|PubMed:21376736, ECO:0000269|PubMed:21840391, ECO:0000269|PubMed:9353331}. |
| Q9NPF0 | CD320 | S81 | Sugiyama | CD320 antigen (8D6 antigen) (FDC-signaling molecule 8D6) (FDC-SM-8D6) (Transcobalamin receptor) (TCblR) (CD antigen CD320) | Receptor for transcobalamin saturated with cobalamin (TCbl) (PubMed:18779389). Plays an important role in cobalamin uptake (PubMed:18779389, PubMed:20524213). Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells (PubMed:10727470). Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation (PubMed:10727470, PubMed:11418631). Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC) (PubMed:11418631). CD320 augments the proliferation of PC precursors generated by IL-10 (PubMed:11418631). {ECO:0000269|PubMed:10727470, ECO:0000269|PubMed:11418631, ECO:0000269|PubMed:18779389, ECO:0000269|PubMed:20524213}. |
| Q9HBH9 | MKNK2 | S394 | Sugiyama | MAP kinase-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (MAP kinase signal-integrating kinase 2) (MAPK signal-integrating kinase 2) (Mnk2) | Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}. |
| Q9NRM7 | LATS2 | S829 | Sugiyama | Serine/threonine-protein kinase LATS2 (EC 2.7.11.1) (Kinase phosphorylated during mitosis protein) (Large tumor suppressor homolog 2) (Serine/threonine-protein kinase kpm) (Warts-like kinase) | Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:18158288, PubMed:26437443, PubMed:26598551, PubMed:34404733). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:26437443, PubMed:26598551, PubMed:34404733). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:26598551, PubMed:34404733). Also phosphorylates YAP1 in response to cell contact inhibition-driven WWP1 ubiquitination of AMOTL2, which results in LATS2 activation (PubMed:34404733). Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability (PubMed:10871863). Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity (PubMed:12853976). Negative regulator of the androgen receptor (PubMed:15131260). Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities (PubMed:21952048). This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ (PubMed:21952048). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10871863, ECO:0000269|PubMed:12853976, ECO:0000269|PubMed:15131260, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:39173637}. |
| P10636 | MAPT | S610 | GPS6|EPSD | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| Q9P0L2 | MARK1 | S498 | Sugiyama | Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}. |
| Q9P0L2 | MARK1 | S711 | Sugiyama | Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}. |
| Q9Y6E0 | STK24 | S46 | Sugiyama | Serine/threonine-protein kinase 24 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 3) (MST-3) (STE20-like kinase MST3) [Cleaved into: Serine/threonine-protein kinase 24 36 kDa subunit (Mammalian STE20-like protein kinase 3 N-terminal) (MST3/N); Serine/threonine-protein kinase 24 12 kDa subunit (Mammalian STE20-like protein kinase 3 C-terminal) (MST3/C)] | Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Also regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:16314523, ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:19782762, ECO:0000269|PubMed:19855390, ECO:0000269|PubMed:27807006}. |
| P56192 | MARS1 | S472 | EPSD|PSP | Methionine--tRNA ligase, cytoplasmic (EC 6.1.1.10) (Methionyl-tRNA synthetase) (MetRS) | Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:11714285). Plays a role in the synthesis of ribosomal RNA in the nucleolus (PubMed:10791971). {ECO:0000269|PubMed:10791971, ECO:0000269|PubMed:11714285, ECO:0000269|PubMed:33909043}. |
| Q9UBE8 | NLK | S237 | Sugiyama | Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1) | Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}. |
| Q9UK32 | RPS6KA6 | S318 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| Q9UK32 | RPS6KA6 | S555 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| P29401 | TKT | S124 | Sugiyama | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| Q8IW41 | MAPKAPK5 | S160 | SIGNOR|PSP | MAP kinase-activated protein kinase 5 (MAPK-activated protein kinase 5) (MAPKAP kinase 5) (MAPKAP-K5) (MAPKAPK-5) (MK-5) (MK5) (EC 2.7.11.1) (p38-regulated/activated protein kinase) (PRAK) | Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}. |
| Q7L7X3 | TAOK1 | S38 | Sugiyama | Serine/threonine-protein kinase TAO1 (EC 2.7.11.1) (Kinase from chicken homolog B) (hKFC-B) (MARK Kinase) (MARKK) (Prostate-derived sterile 20-like kinase 2) (PSK-2) (PSK2) (Prostate-derived STE20-like kinase 2) (Thousand and one amino acid protein kinase 1) (TAOK1) (hTAOK1) | Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system (PubMed:33565190). Also plays a role in the regulation of neuronal migration to the cortical plate (By similarity). {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936, ECO:0000269|PubMed:33565190}. |
| Q9UL54 | TAOK2 | S38 | Sugiyama | Serine/threonine-protein kinase TAO2 (EC 2.7.11.1) (Kinase from chicken homolog C) (hKFC-C) (Prostate-derived sterile 20-like kinase 1) (PSK-1) (PSK1) (Prostate-derived STE20-like kinase 1) (Thousand and one amino acid protein kinase 2) | Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17396146}. |
| Q9UM73 | ALK | S1538 | Sugiyama | ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) | Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}. |
| Q9H7E2 | TDRD3 | S358 | Sugiyama | Tudor domain-containing protein 3 | Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins (PubMed:15955813). Plays a role in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci (PubMed:21172665). In cytoplasm, acts as an antiviral factor that participates in the assembly of stress granules together with G3BP1 (PubMed:35085371). {ECO:0000269|PubMed:15955813, ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:21172665, ECO:0000269|PubMed:35085371}. |
| Q8IZ83 | ALDH16A1 | S427 | Sugiyama | Aldehyde dehydrogenase family 16 member A1 | None |
| Q8N6H7 | ARFGAP2 | S123 | Sugiyama | ADP-ribosylation factor GTPase-activating protein 2 (ARF GAP 2) (GTPase-activating protein ZNF289) (Zinc finger protein 289) | GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. {ECO:0000269|PubMed:17760859}. |
| P35372 | OPRM1 | S270 | SIGNOR | Mu-type opioid receptor (M-OR-1) (MOR-1) (Mu opiate receptor) (Mu opioid receptor) (MOP) (hMOP) | Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity). {ECO:0000250|UniProtKB:P33535, ECO:0000269|PubMed:10529478, ECO:0000269|PubMed:12068084, ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, ECO:0000303|PubMed:19300905}.; FUNCTION: [Isoform 12]: Couples to GNAS and is proposed to be involved in excitatory effects. {ECO:0000269|PubMed:20525224}.; FUNCTION: [Isoform 16]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}.; FUNCTION: [Isoform 17]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}. |
| A0A0A0MRY4 | None | S617 | ochoa | Spermatogenesis-associated protein 13 | None |
| A0A0A6YYC7 | ZFP91-CNTF | S177 | ochoa | E3 ubiquitin-protein ligase ZFP91 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase ZFP91) (Zinc finger protein 91 homolog) | Atypical E3 ubiquitin-protein ligase that mediates 'Lys-63'-linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate MAP3K14/NIK. It thereby acts as an activator of the non-canonical NF-kappa-B2/NFKB2 pathway. May also play an important role in cell proliferation and/or anti-apoptosis. {ECO:0000256|ARBA:ARBA00054990}. |
| A0A0B4J203 | None | S112 | ochoa | receptor protein-tyrosine kinase (EC 2.7.10.1) | None |
| A0AVK6 | E2F8 | S52 | ochoa | Transcription factor E2F8 (E2F-8) | Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. {ECO:0000269|PubMed:15897886, ECO:0000269|PubMed:16179649, ECO:0000269|PubMed:18202719, ECO:0000269|PubMed:22903062}. |
| A0FGR8 | ESYT2 | S821 | ochoa | Extended synaptotagmin-2 (E-Syt2) (Chr2Syt) | Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}. |
| A1L390 | PLEKHG3 | S647 | ochoa | Pleckstrin homology domain-containing family G member 3 (PH domain-containing family G member 3) | Plays a role in controlling cell polarity and cell motility by selectively binding newly polymerized actin and activating RAC1 and CDC42 to enhance local actin polymerization. {ECO:0000269|PubMed:27555588}. |
| A2RTX5 | TARS3 | S675 | ochoa | Threonine--tRNA ligase 2, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase protein 3) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage. {ECO:0000250|UniProtKB:Q8BLY2}. |
| A6NF01 | POM121B | S84 | ochoa | Putative nuclear envelope pore membrane protein POM 121B | Putative component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane (By similarity). {ECO:0000250}. |
| A6NKT7 | RGPD3 | S1543 | ochoa | RanBP2-like and GRIP domain-containing protein 3 | None |
| A6NNZ2 | TUBB8B | S278 | ochoa | Tubulin beta 8B | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| A8CG34 | POM121C | S76 | ochoa | Nuclear envelope pore membrane protein POM 121C (Nuclear pore membrane protein 121-2) (POM121-2) (Pore membrane protein of 121 kDa C) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| A8CG34 | POM121C | S477 | ochoa | Nuclear envelope pore membrane protein POM 121C (Nuclear pore membrane protein 121-2) (POM121-2) (Pore membrane protein of 121 kDa C) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| B4DLN1 | None | S248 | ochoa | Mitochondrial dicarboxylate carrier (Solute carrier family 25 member 10) | Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across mitochondrial inner membrane. Plays an important role in gluconeogenesis, fatty acid metabolism, urea synthesis, and sulfur metabolism, particularly in liver, by supplying the substrates for the different metabolic processes. Regulates fatty acid release from adipocytes, and contributes to systemic insulin sensitivity. {ECO:0000256|ARBA:ARBA00057945}. |
| D6RIA3 | C4orf54 | S1035 | ochoa | Uncharacterized protein C4orf54 (Familial obliterative portal venopathy) | None |
| O00139 | KIF2A | S207 | ochoa | Kinesin-like protein KIF2A (Kinesin-2) (hK2) | Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity. {ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:30785839}. |
| O00159 | MYO1C | S29 | ochoa | Unconventional myosin-Ic (Myosin I beta) (MMI-beta) (MMIb) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: [Isoform 3]: Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation. {ECO:0000250|UniProtKB:Q9WTI7}. |
| O00159 | MYO1C | S916 | ochoa | Unconventional myosin-Ic (Myosin I beta) (MMI-beta) (MMIb) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: [Isoform 3]: Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation. {ECO:0000250|UniProtKB:Q9WTI7}. |
| O00192 | ARVCF | S335 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00287 | RFXAP | S193 | ochoa | Regulatory factor X-associated protein (RFX-associated protein) (RFX DNA-binding complex 36 kDa subunit) | Part of the RFX complex that binds to the X-box of MHC II promoters. |
| O00401 | WASL | S19 | ochoa | Actin nucleation-promoting factor WASL (Neural Wiskott-Aldrich syndrome protein) (N-WASP) | Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex (PubMed:16767080, PubMed:19366662, PubMed:19487689, PubMed:22847007, PubMed:22921828, PubMed:9422512). Involved in various processes, such as mitosis and cytokinesis, via its role in the regulation of actin polymerization (PubMed:19366662, PubMed:19487689, PubMed:22847007, PubMed:22921828, PubMed:9422512). Together with CDC42, involved in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia (PubMed:9422512). In addition to its role in the cytoplasm, also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization (PubMed:16767080). Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression (By similarity). Plays a role in dendrite spine morphogenesis (By similarity). Decreasing levels of DNMBP (using antisense RNA) alters apical junction morphology in cultured enterocytes, junctions curve instead of being nearly linear (PubMed:19767742). {ECO:0000250|UniProtKB:Q91YD9, ECO:0000269|PubMed:16767080, ECO:0000269|PubMed:19366662, ECO:0000269|PubMed:19487689, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:22847007, ECO:0000269|PubMed:22921828, ECO:0000269|PubMed:9422512}. |
| O00478 | BTN3A3 | S213 | ochoa | Butyrophilin subfamily 3 member A3 | Plays a role in T-cell responses in the adaptive immune response. {ECO:0000269|PubMed:22767497}. |
| O00499 | BIN1 | S276 | ochoa | Myc box-dependent-interacting protein 1 (Amphiphysin II) (Amphiphysin-like protein) (Box-dependent myc-interacting protein 1) (Bridging integrator 1) | Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling (PubMed:24755653). Is a negative regulator of endocytosis (By similarity). Is also involved in the regulation of intracellular vesicles sorting, modulation of BACE1 trafficking and the control of amyloid-beta production (PubMed:27179792). In neuronal circuits, endocytosis regulation may influence the internalization of PHF-tau aggregates (By similarity). May be involved in the regulation of MYC activity and the control cell proliferation (PubMed:8782822). Has actin bundling activity and stabilizes actin filaments against depolymerization in vitro (PubMed:28893863). {ECO:0000250|UniProtKB:O08839, ECO:0000269|PubMed:24755653, ECO:0000269|PubMed:27179792, ECO:0000269|PubMed:28893863, ECO:0000269|PubMed:8782822}. |
| O00515 | LAD1 | S251 | ochoa | Ladinin-1 (Lad-1) (Linear IgA disease antigen) (LADA) | Anchoring filament protein which is a component of the basement membrane zone. {ECO:0000250}. |
| O00567 | NOP56 | S314 | ochoa | Nucleolar protein 56 (Nucleolar protein 5A) | Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs (PubMed:12777385, PubMed:15574333). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:12777385, PubMed:39570315). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| O00571 | DDX3X | S583 | ochoa | ATP-dependent RNA helicase DDX3X (EC 3.6.4.13) (CAP-Rf) (DEAD box protein 3, X-chromosomal) (DEAD box, X isoform) (DBX) (Helicase-like protein 2) (HLP2) | Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:17667941, PubMed:18628297, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150). This function depends on helicase activity (PubMed:20837705, PubMed:22872150). Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705). Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150). Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517). Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705). May activate TP53 translation (PubMed:28842590). Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517). Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941). Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:20127681, PubMed:21170385, PubMed:31575075). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385, PubMed:33674311). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:19913487, PubMed:21170385, PubMed:27980081). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265). Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167). Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167). Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973). May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960). Involved in both stress and inflammatory responses (By similarity). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity). Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110). Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110). Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110). ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110). May be involved in mitotic chromosome segregation (PubMed:21730191). {ECO:0000250|UniProtKB:Q62167, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17095540, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:27736973, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29222110, ECO:0000269|PubMed:30256975, ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:31575075, ECO:0000269|PubMed:33674311, ECO:0000305}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385). {ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960). {ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication. {ECO:0000269|PubMed:27105836}. |
| O00757 | FBP2 | S238 | ochoa | Fructose-1,6-bisphosphatase isozyme 2 (FBPase 2) (EC 3.1.3.11) (D-fructose-1,6-bisphosphate 1-phosphohydrolase 2) (Muscle FBPase) | Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate. {ECO:0000269|PubMed:17350621, ECO:0000269|PubMed:18214967, ECO:0000269|PubMed:33977262}. |
| O14523 | C2CD2L | S59 | ochoa | Phospholipid transfer protein C2CD2L (C2 domain-containing protein 2-like) (C2CD2-like) (Transmembrane protein 24) | Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}. |
| O14526 | FCHO1 | S622 | ochoa | F-BAR domain only protein 1 | Functions in an early step of clathrin-mediated endocytosis (PubMed:30822429). Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. May regulate Bmp signaling by regulating clathrin-mediated endocytosis of Bmp receptors. Involved in the regulation of T-cell poliferation and activation (PubMed:30822429, PubMed:32098969). Affects TCR clustering upon receptor triggering and modulates its internalisation, playing a role in TCR-dependent T-cell activation (PubMed:32098969). {ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:30822429, ECO:0000269|PubMed:32098969}. |
| O14562 | UBFD1 | S108 | ochoa | Ubiquitin domain-containing protein UBFD1 (Ubiquitin-binding protein homolog) | May play a role as NF-kappa-B regulator. {ECO:0000269|PubMed:19285159}. |
| O14787 | TNPO2 | S355 | ochoa | Transportin-2 (Karyopherin beta-2b) | Probably functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). {ECO:0000250}. |
| O14936 | CASK | S562 | ochoa | Peripheral plasma membrane protein CASK (hCASK) (EC 2.7.11.1) (Calcium/calmodulin-dependent serine protein kinase) (Protein lin-2 homolog) | Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking (PubMed:18423203). Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). {ECO:0000250|UniProtKB:O70589, ECO:0000269|PubMed:18423203}. |
| O15014 | ZNF609 | S777 | ochoa | Zinc finger protein 609 | Transcription factor, which activates RAG1, and possibly RAG2, transcription. Through the regulation of RAG1/2 expression, may regulate thymocyte maturation. Along with NIPBL and the multiprotein complex Integrator, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others. {ECO:0000250|UniProtKB:Q8BZ47}.; FUNCTION: [Isoform 2]: Involved in the regulation of myoblast proliferation during myogenesis. {ECO:0000269|PubMed:28344082}. |
| O15027 | SEC16A | S1327 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15054 | KDM6B | S971 | ochoa | Lysine-specific demethylase 6B (EC 1.14.11.68) (JmjC domain-containing protein 3) (Jumonji domain-containing protein 3) (Lysine demethylase 6B) ([histone H3]-trimethyl-L-lysine(27) demethylase 6B) | Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity). {ECO:0000250|UniProtKB:Q5NCY0, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17825402, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914, ECO:0000269|PubMed:28262558}. |
| O15061 | SYNM | S904 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15061 | SYNM | S981 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15061 | SYNM | S1489 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15067 | PFAS | S83 | ochoa | Phosphoribosylformylglycinamidine synthase (FGAM synthase) (FGAMS) (EC 6.3.5.3) (Formylglycinamide ribonucleotide amidotransferase) (FGAR amidotransferase) (FGAR-AT) (Formylglycinamide ribotide amidotransferase) (Phosphoribosylformylglycineamide amidotransferase) | Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate. {ECO:0000305|PubMed:10548741}. |
| O15085 | ARHGEF11 | S592 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15117 | FYB1 | S558 | ochoa | FYN-binding protein 1 (Adhesion and degranulation promoting adaptor protein) (ADAP) (FYB-120/130) (p120/p130) (FYN-T-binding protein) (SLAP-130) (SLP-76-associated phosphoprotein) | Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells (By similarity). May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton (PubMed:10747096, PubMed:16980616). Modulates the expression of IL2 (By similarity). Involved in platelet activation (By similarity). Prevents the degradation of SKAP1 and SKAP2 (PubMed:15849195). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (By similarity). {ECO:0000250|UniProtKB:D3ZIE4, ECO:0000250|UniProtKB:O35601, ECO:0000269|PubMed:10747096, ECO:0000269|PubMed:15849195, ECO:0000269|PubMed:16980616}. |
| O15389 | SIGLEC5 | S490 | ochoa | Sialic acid-binding Ig-like lectin 5 (Siglec-5) (CD33 antigen-like 2) (Obesity-binding protein 2) (OB-BP2) (OB-binding protein 2) (CD antigen CD170) | Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Binds equally to alpha-2,3-linked and alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. |
| O15432 | SLC31A2 | S77 | ochoa | Protein SLC31A2 (Copper transporter 2) (hCTR2) (Solute carrier family 31 member 2) | Does not function as a copper(1+) importer in vivo (By similarity). However, in vitro functions as a low-affinity copper(1+) importer (PubMed:17617060, PubMed:17944601). Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1 (By similarity). {ECO:0000250|UniProtKB:Q9CPU9, ECO:0000269|PubMed:17617060, ECO:0000269|PubMed:17944601}. |
| O15446 | POLR1G | S66 | ochoa | DNA-directed RNA polymerase I subunit RPA34 (A34.5) (Antisense to ERCC-1 protein) (ASE-1) (CD3-epsilon-associated protein) (CD3E-associated protein) (DNA-directed RNA polymerase I subunit G) (RNA polymerase I-associated factor PAF49) | Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Involved in UBTF-activated transcription, presumably at a step following PIC formation. {ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492}.; FUNCTION: [Isoform 2]: Has been described as a component of preformed T-cell receptor (TCR) complex. {ECO:0000269|PubMed:10373416}. |
| O43396 | TXNL1 | S113 | ochoa | Thioredoxin-like protein 1 (32 kDa thioredoxin-related protein) | Active thioredoxin with a redox potential of about -250 mV. {ECO:0000269|PubMed:19349277}. |
| O43432 | EIF4G3 | S1131 | ochoa | Eukaryotic translation initiation factor 4 gamma 3 (eIF-4-gamma 3) (eIF-4G 3) (eIF4G 3) (eIF-4-gamma II) (eIF4GII) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:9418880). Functional homolog of EIF4G1 (PubMed:9418880). {ECO:0000269|PubMed:9418880}. |
| O43504 | LAMTOR5 | S26 | ochoa|psp | Ragulator complex protein LAMTOR5 (Hepatitis B virus X-interacting protein) (HBV X-interacting protein) (HBX-interacting protein) (Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5) | As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:22980980, PubMed:29158492, PubMed:30181260). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29158492, PubMed:30181260). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:22980980, PubMed:29158492, PubMed:30181260). When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway (PubMed:12773388). {ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29107538, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:30181260}. |
| O43598 | DNPH1 | S28 | ochoa | 5-hydroxymethyl-dUMP N-hydrolase (EC 3.2.2.-) (2'-deoxynucleoside 5'-phosphate N-hydrolase 1) (c-Myc-responsive protein RCL) | Part of a nucleotide salvage pathway that eliminates epigenetically modified 5-hydroxymethyl-dCMP (hmdCMP) in a two-step process entailing deamination to cytotoxic 5-hydroxymethyl-dUMP (hmdUMP), followed by its hydrolysis into 5-hydroxymethyluracil (hmU) and 2-deoxy-D-ribose 5-phosphate (deoxyribosephosphate) (PubMed:33833118). Catalyzes the second step in that pathway, the hydrolysis of the N-glycosidic bond in hmdUMP, degrading this cytotoxic nucleotide to avoid its genomic integration (PubMed:33833118). {ECO:0000269|PubMed:33833118}. |
| O43609 | SPRY1 | S169 | ochoa | Protein sprouty homolog 1 (Spry-1) | Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q9QXV9}. |
| O43663 | PRC1 | S563 | ochoa | Protein regulator of cytokinesis 1 | Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}. |
| O43752 | STX6 | S129 | ochoa | Syntaxin-6 | SNARE promoting movement of transport vesicles to target membranes. Targets endosomes to the trans-Golgi network, and may therefore function in retrograde trafficking. Together with SNARE STX12, promotes movement of vesicles from endosomes to the cell membrane, and may therefore function in the endocytic recycling pathway. {ECO:0000250|UniProtKB:Q63635}. |
| O60237 | PPP1R12B | S29 | ochoa | Protein phosphatase 1 regulatory subunit 12B (Myosin phosphatase-targeting subunit 2) (Myosin phosphatase target subunit 2) | Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus. {ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:9570949}. |
| O60271 | SPAG9 | S1188 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60292 | SIPA1L3 | S1238 | ochoa | Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}. |
| O60292 | SIPA1L3 | S1306 | ochoa | Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}. |
| O60306 | AQR | S956 | ochoa | RNA helicase aquarius (EC 3.6.4.13) (Intron-binding protein of 160 kDa) (IBP160) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:25599396, PubMed:28076346, PubMed:28502770). Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis (PubMed:16949364). Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly (PubMed:16949364). May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing (PubMed:16949364). Has ATP-dependent RNA helicase activity and can unwind double-stranded RNA molecules with a 3' overhang (in vitro) (PubMed:25599396). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:16949364, ECO:0000269|PubMed:25599396, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}. |
| O60307 | MAST3 | S680 | ochoa | Microtubule-associated serine/threonine-protein kinase 3 (EC 2.7.11.1) | None |
| O60333 | KIF1B | S1603 | ochoa | Kinesin-like protein KIF1B (Klp) (EC 5.6.1.3) | Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules. {ECO:0000269|PubMed:16225668}.; FUNCTION: [Isoform 2]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde synaptic vesicle transport along axonal microtubules from the cell body to the presynapse in neuronal cells (By similarity). Functions as a downstream effector in a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells (PubMed:18334619). {ECO:0000250|UniProtKB:Q60575, ECO:0000269|PubMed:18334619}.; FUNCTION: [Isoform 3]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde transport of mitochondria. {ECO:0000269|PubMed:16225668}. |
| O60353 | FZD6 | S641 | ochoa | Frizzled-6 (Fz-6) (hFz6) | Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q61089}. |
| O60565 | GREM1 | S137 | ochoa | Gremlin-1 (Cell proliferation-inducing gene 2 protein) (Cysteine knot superfamily 1, BMP antagonist 1) (DAN domain family member 2) (Down-regulated in Mos-transformed cells protein) (Increased in high glucose protein 2) (IHG-2) | Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner (By similarity). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (PubMed:27036124). Acts as inhibitor of monocyte chemotaxis. Can inhibit the growth or viability of normal cells but not transformed cells when is overexpressed (By similarity). {ECO:0000250|UniProtKB:O35793, ECO:0000250|UniProtKB:O70326, ECO:0000269|PubMed:27036124}. |
| O60664 | PLIN3 | S241 | ochoa | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| O60716 | CTNND1 | S230 | ochoa | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60763 | USO1 | S717 | ochoa | General vesicular transport factor p115 (Protein USO1 homolog) (Transcytosis-associated protein) (TAP) (Vesicle-docking protein) | General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. May well act as a vesicular anchor by interacting with the target membrane and holding the vesicular and target membranes in proximity. {ECO:0000250|UniProtKB:P41542}. |
| O75044 | SRGAP2 | S900 | ochoa | SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) (Formin-binding protein 2) (Rho GTPase-activating protein 34) | Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:20810653, PubMed:27373832, PubMed:28333212). Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (By similarity). Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:27373832). Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (By similarity). In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:20810653, PubMed:21148482). {ECO:0000250|UniProtKB:Q91Z67, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944, ECO:0000269|PubMed:27373832, ECO:0000269|PubMed:28333212}. |
| O75064 | DENND4B | S963 | ochoa | DENN domain-containing protein 4B | Guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}. |
| O75122 | CLASP2 | S364 | ochoa | CLIP-associating protein 2 (Cytoplasmic linker-associated protein 2) (Protein Orbit homolog 2) (hOrbit2) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules (PubMed:26003921). Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2 (PubMed:16824950). This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (PubMed:16866869, PubMed:16914514). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16824950, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:26003921}. |
| O75128 | COBL | S47 | ochoa | Protein cordon-bleu | Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. {ECO:0000250, ECO:0000269|PubMed:21816349}. |
| O75140 | DEPDC5 | S579 | ochoa | GATOR1 complex protein DEPDC5 (DEP domain-containing protein 5) | As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:25457612, PubMed:29590090, PubMed:29769719, PubMed:31548394, PubMed:35338845). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (PubMed:23723238, PubMed:25457612, PubMed:29590090, PubMed:29769719, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway (PubMed:23723238, PubMed:25457612, PubMed:29769719). Within the GATOR1 complex, DEPDC5 mediates direct interaction with the nucleotide-binding pocket of small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and coordinates their nucleotide loading states by promoting RagA/RRAGA or RagB/RRAGB into their GDP-binding state and RagC/RRAGC or RagD/RRAGD into their GTP-binding state (PubMed:29590090, PubMed:35338845). However, it does not execute the GAP activity, which is mediated by NPRL2 (PubMed:29590090). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:29590090, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:35338845}. |
| O75145 | PPFIA3 | S512 | ochoa | Liprin-alpha-3 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-3) (PTPRF-interacting protein alpha-3) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:9624153}. |
| O75167 | PHACTR2 | S23 | ochoa | Phosphatase and actin regulator 2 | None |
| O75362 | ZNF217 | S441 | ochoa | Zinc finger protein 217 | Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}. |
| O75362 | ZNF217 | S445 | ochoa | Zinc finger protein 217 | Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}. |
| O75369 | FLNB | S1382 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75376 | NCOR1 | S1164 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75376 | NCOR1 | S1381 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75376 | NCOR1 | S1742 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75475 | PSIP1 | S482 | ochoa | PC4 and SFRS1-interacting protein (CLL-associated antigen KW-7) (Dense fine speckles 70 kDa protein) (DFS 70) (Lens epithelium-derived growth factor) (Transcriptional coactivator p75/p52) | Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration. {ECO:0000269|PubMed:15642333}. |
| O75665 | OFD1 | S720 | ochoa | Centriole and centriolar satellite protein OFD1 (Oral-facial-digital syndrome 1 protein) (Protein 71-7A) | Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250|UniProtKB:Q80Z25, ECO:0000269|PubMed:33934390}. |
| O75815 | BCAR3 | S395 | ochoa | Breast cancer anti-estrogen resistance protein 3 (Novel SH2-containing protein 2) (SH2 domain-containing protein 3B) | Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:24216110). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (PubMed:24216110). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:19086031). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (By similarity). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis (PubMed:18722344). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (By similarity). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By similarity). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By similarity). However, in a contrasting study, lacks GEF activity towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5, ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014, ECO:0000269|PubMed:24216110}. |
| O75821 | EIF3G | S264 | ochoa | Eukaryotic translation initiation factor 3 subunit G (eIF3g) (Eukaryotic translation initiation factor 3 RNA-binding subunit) (eIF-3 RNA-binding subunit) (Eukaryotic translation initiation factor 3 subunit 4) (eIF-3-delta) (eIF3 p42) (eIF3 p44) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). This subunit can bind 18S rRNA. {ECO:0000255|HAMAP-Rule:MF_03006, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| O94776 | MTA2 | S352 | ochoa | Metastasis-associated protein MTA2 (Metastasis-associated 1-like 1) (MTA1-L1 protein) (p53 target protein in deacetylase complex) | May function as a transcriptional coregulator (PubMed:16428440, PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| O94804 | STK10 | S469 | ochoa | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
| O94806 | PRKD3 | S44 | ochoa | Serine/threonine-protein kinase D3 (EC 2.7.11.13) (Protein kinase C nu type) (Protein kinase EPK2) (nPKC-nu) | Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress (By similarity). {ECO:0000250}. |
| O94887 | FARP2 | S339 | ochoa | FERM, ARHGEF and pleckstrin domain-containing protein 2 (FERM domain-including RhoGEF) (FIR) (FERM, RhoGEF and pleckstrin domain-containing protein 2) (Pleckstrin homology domain-containing family C member 3) (PH domain-containing family C member 3) | Functions as a guanine nucleotide exchange factor that activates RAC1. May have relatively low activity. Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton. Plays a role in TNFSF11-mediated osteoclast differentiation, especially in podosome rearrangement and reorganization of the actin cytoskeleton. Regulates the activation of ITGB3, integrin signaling and cell adhesion (By similarity). {ECO:0000250}. |
| O94903 | PLPBP | S244 | ochoa | Pyridoxal phosphate homeostasis protein (PLP homeostasis protein) (Proline synthase co-transcribed bacterial homolog protein) (Pyridoxal phosphate-binding protein) | Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6. {ECO:0000255|HAMAP-Rule:MF_03225, ECO:0000269|PubMed:27912044}. |
| O95049 | TJP3 | S568 | ochoa | Tight junction protein ZO-3 (Tight junction protein 3) (Zona occludens protein 3) (Zonula occludens protein 3) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}. |
| O95239 | KIF4A | S1139 | ochoa | Chromosome-associated kinesin KIF4A (Chromokinesin-A) | Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (PubMed:29848660). Translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis (PubMed:15297875, PubMed:15625105). May play a role in mitotic chromosomal positioning and bipolar spindle stabilization (By similarity). {ECO:0000250|UniProtKB:P33174, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:29848660}. |
| O95466 | FMNL1 | S909 | ochoa | Formin-like protein 1 (CLL-associated antigen KW-13) (Leukocyte formin) | May play a role in the control of cell motility and survival of macrophages (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| O95714 | HERC2 | S2942 | ochoa | E3 ubiquitin-protein ligase HERC2 (EC 2.3.2.26) (HECT domain and RCC1-like domain-containing protein 2) (HECT-type E3 ubiquitin transferase HERC2) | E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). Also modulates iron metabolism by regulating the basal turnover of FBXL5 (PubMed:24778179). {ECO:0000269|PubMed:20023648, ECO:0000269|PubMed:20304803, ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:24778179, ECO:0000269|PubMed:26692333}. |
| O95721 | SNAP29 | S105 | psp | Synaptosomal-associated protein 29 (SNAP-29) (Soluble 29 kDa NSF attachment protein) (Vesicle-membrane fusion protein SNAP-29) | SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions. {ECO:0000269|PubMed:23217709, ECO:0000269|PubMed:25686250, ECO:0000269|PubMed:25686604}. |
| O95789 | ZMYM6 | S759 | ochoa | Zinc finger MYM-type protein 6 (Transposon-derived Buster2 transposase-like protein) (Zinc finger protein 258) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| O95810 | CAVIN2 | S89 | ochoa | Caveolae-associated protein 2 (Cavin-2) (PS-p68) (Phosphatidylserine-binding protein) (Serum deprivation-response protein) | Plays an important role in caveolar biogenesis and morphology. Regulates caveolae morphology by inducing membrane curvature within caveolae (PubMed:19525939). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in the lung and fat endothelia but not in the heart endothelia. Negatively regulates the size or stability of CAVIN complexes in the lung endothelial cells. May play a role in targeting PRKCA to caveolae (By similarity). {ECO:0000250|UniProtKB:Q66H98, ECO:0000269|PubMed:19525939}. |
| O95822 | MLYCD | S471 | ochoa | Malonyl-CoA decarboxylase, mitochondrial (MCD) (EC 4.1.1.9) | Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation. {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260, ECO:0000269|PubMed:18314420, ECO:0000269|PubMed:23482565}. |
| O95835 | LATS1 | S1107 | ochoa | Serine/threonine-protein kinase LATS1 (EC 2.7.11.1) (Large tumor suppressor homolog 1) (WARTS protein kinase) (h-warts) | Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:10518011, PubMed:10831611, PubMed:18158288, PubMed:26437443, PubMed:28068668). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288, PubMed:26437443, PubMed:28068668). Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288, PubMed:26437443, PubMed:28068668). Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint (PubMed:15122335, PubMed:19927127). Negatively regulates G2/M transition by down-regulating CDK1 kinase activity (PubMed:9988268). Involved in the control of p53 expression (PubMed:15122335). Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1 (PubMed:15220930). May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:10831611, ECO:0000269|PubMed:15122335, ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:28068668, ECO:0000269|PubMed:39173637, ECO:0000269|PubMed:9988268}. |
| O95983 | MBD3 | S56 | ochoa | Methyl-CpG-binding domain protein 3 (Methyl-CpG-binding protein MBD3) | Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:12124384, PubMed:16428440, PubMed:28977666). Acts as transcriptional repressor and plays a role in gene silencing (PubMed:10947852, PubMed:18644863). Does not bind to methylated DNA by itself (PubMed:12124384, PubMed:16428440). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA methyltransferases. {ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:12124384, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:18644863, ECO:0000269|PubMed:23361464, ECO:0000269|PubMed:24307175, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:9774669}. |
| O96018 | APBA3 | S46 | ochoa | Amyloid-beta A4 precursor protein-binding family A member 3 (Adapter protein X11gamma) (Neuron-specific X11L2 protein) (Neuronal Munc18-1-interacting protein 3) (Mint-3) | May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. May enhance the activity of HIF1A in macrophages by inhibiting the activity of HIF1AN. {ECO:0000269|PubMed:19726677}. |
| O96019 | ACTL6A | S51 | ochoa | Actin-like protein 6A (53 kDa BRG1-associated factor A) (Actin-related protein Baf53a) (ArpNbeta) (BRG1-associated factor 53A) (BAF53A) (INO80 complex subunit K) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Required for maximal ATPase activity of SMARCA4/BRG1/BAF190A and for association of the SMARCA4/BRG1/BAF190A containing remodeling complex BAF with chromatin/nuclear matrix. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Putative core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. {ECO:0000250|UniProtKB:Q9Z2N8, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:29374058, ECO:0000303|PubMed:15196461, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P00519 | ABL1 | S708 | ochoa | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P02671 | FGA | S364 | ochoa|psp | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P02671 | FGA | S489 | ochoa | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P04049 | RAF1 | S359 | psp | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. |
| P04350 | TUBB4A | S278 | ochoa | Tubulin beta-4A chain (Tubulin 5 beta) (Tubulin beta-4 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P04920 | SLC4A2 | S449 | ochoa | Anion exchange protein 2 (AE 2) (Anion exchanger 2) (Non-erythroid band 3-like protein) (BND3L) (Solute carrier family 4 member 2) | Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15184086, PubMed:34668226). Plays an important role in osteoclast differentiation and function (PubMed:34668226). Regulates bone resorption and calpain-dependent actin cytoskeleton organization in osteoclasts via anion exchange-dependent control of pH (By similarity). Essential for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation, modulating CD8(+) T-cell responses (By similarity). {ECO:0000250|UniProtKB:P13808, ECO:0000269|PubMed:15184086, ECO:0000269|PubMed:34668226}. |
| P05771 | PRKCB | S120 | ochoa | Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}. |
| P06239 | LCK | S162 | ochoa | Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) | Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}. |
| P06241 | FYN | S21 | ochoa|psp | Tyrosine-protein kinase Fyn (EC 2.7.10.2) (Proto-oncogene Syn) (Proto-oncogene c-Fyn) (Src-like kinase) (SLK) (p59-Fyn) | Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance (PubMed:11536198, PubMed:15489916, PubMed:15557120, PubMed:16387660, PubMed:20100835, PubMed:7568038, PubMed:7822789). Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain (PubMed:15489916). Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions (PubMed:15489916). Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin) (PubMed:17194753). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT (PubMed:14707117, PubMed:15536091). Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage (PubMed:16841086). Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6 (PubMed:14761972, PubMed:18258597, PubMed:19179337). Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein (PubMed:11162638, PubMed:12788081, PubMed:19652227). Involved in reelin signaling by mediating phosphorylation of DAB1 following reelin (RELN)-binding to its receptor (By similarity). Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation (PubMed:22080863). Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation (PubMed:20028775). Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts (PubMed:18056706). CSK maintains LCK and FYN in an inactive form (By similarity). Promotes CD28-induced phosphorylation of VAV1 (PubMed:11005864). In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (By similarity). Can also promote CD244-mediated NK cell activation (PubMed:15713798). {ECO:0000250|UniProtKB:P39688, ECO:0000269|PubMed:11005864, ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11536198, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:14707117, ECO:0000269|PubMed:14761972, ECO:0000269|PubMed:15536091, ECO:0000269|PubMed:15557120, ECO:0000269|PubMed:15713798, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:16841086, ECO:0000269|PubMed:17194753, ECO:0000269|PubMed:18056706, ECO:0000269|PubMed:18258597, ECO:0000269|PubMed:19179337, ECO:0000269|PubMed:19652227, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:7568038, ECO:0000269|PubMed:7822789, ECO:0000303|PubMed:15489916}. |
| P06576 | ATP5F1B | S316 | ochoa | ATP synthase F(1) complex subunit beta, mitochondrial (EC 7.1.2.2) (ATP synthase F1 subunit beta) | Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable) (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain (PubMed:37244256). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:25168243, ECO:0000305|PubMed:36239646, ECO:0000305|PubMed:37244256}. |
| P07437 | TUBB | S278 | ochoa | Tubulin beta chain (Tubulin beta-5 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P07451 | CA3 | S99 | ochoa | Carbonic anhydrase 3 (EC 4.2.1.1) (Carbonate dehydratase III) (Carbonic anhydrase III) (CA-III) | Reversible hydration of carbon dioxide. {ECO:0000269|PubMed:17427958, ECO:0000269|PubMed:18618712}. |
| P07900 | HSP90AA1 | S169 | ochoa | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| P07949 | RET | S832 | ochoa | Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment] | Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698). {ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:25242331, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31118272}.; FUNCTION: [Isoform 1]: Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. {ECO:0000269|PubMed:28846099}. |
| P07954 | FH | S365 | ochoa | Fumarate hydratase, mitochondrial (Fumarase) (HsFH) (EC 4.2.1.2) | Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:30761759). Experiments in other species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable). {ECO:0000269|PubMed:30761759, ECO:0000305}.; FUNCTION: [Isoform Mitochondrial]: Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH. {ECO:0000250|UniProtKB:P10173}.; FUNCTION: [Isoform Cytoplasmic]: Catalyzes the dehydration of L-malate to fumarate (By similarity). Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism (By similarity). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (PubMed:20231875, PubMed:26237645). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2) (PubMed:26237645). {ECO:0000250|UniProtKB:P97807, ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:26237645}. |
| P08034 | GJB1 | S258 | ochoa | Gap junction beta-1 protein (Connexin-32) (Cx32) (GAP junction 28 kDa liver protein) | One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. |
| P08238 | HSP90AB1 | S164 | ochoa | Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}. |
| P08581 | MET | S1020 | ochoa | Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}. |
| P09211 | GSTP1 | S43 | psp | Glutathione S-transferase P (EC 2.5.1.18) (GST class-pi) (GSTP1-1) | Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration. {ECO:0000269|PubMed:21046276, ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9084911}. |
| P09417 | QDPR | S226 | ochoa | Dihydropteridine reductase (EC 1.5.1.34) (HDHPR) (Quinoid dihydropteridine reductase) (Short chain dehydrogenase/reductase family 33C member 1) | Catalyzes the conversion of quinonoid dihydrobiopterin into tetrahydrobiopterin. {ECO:0000269|PubMed:3033643, ECO:0000269|PubMed:8262916}. |
| P09467 | FBP1 | S63 | psp | Fructose-1,6-bisphosphatase 1 (FBPase 1) (EC 3.1.3.11) (D-fructose-1,6-bisphosphate 1-phosphohydrolase 1) (Liver FBPase) | Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000269|PubMed:16497803, ECO:0000269|PubMed:18375435, ECO:0000269|PubMed:22517657}. |
| P0DJD0 | RGPD1 | S1527 | ochoa | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P0DJD1 | RGPD2 | S1535 | ochoa | RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) | None |
| P10275 | AR | S206 | ochoa | Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4) | Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:25091737}.; FUNCTION: [Isoform 3]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}.; FUNCTION: [Isoform 4]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}. |
| P12109 | COL6A1 | S766 | ochoa | Collagen alpha-1(VI) chain | Collagen VI acts as a cell-binding protein. |
| P13010 | XRCC5 | S585 | ochoa | X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}. |
| P13611 | VCAN | S566 | ochoa | Versican core protein (Chondroitin sulfate proteoglycan core protein 2) (Chondroitin sulfate proteoglycan 2) (Glial hyaluronate-binding protein) (GHAP) (Large fibroblast proteoglycan) (PG-M) | May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid. |
| P13861 | PRKAR2A | S205 | ochoa | cAMP-dependent protein kinase type II-alpha regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P14618 | PKM | S202 | ochoa|psp | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P14866 | HNRNPL | S298 | ochoa | Heterogeneous nuclear ribonucleoprotein L (hnRNP L) | Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:22570490, PubMed:24164894, PubMed:25623890, PubMed:26051023). Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts (PubMed:2687284). Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter (PubMed:11809897). As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). Regulates alternative splicing of a core group of genes involved in neuronal differentiation, likely by mediating H3K36me3-coupled transcription elongation and co-transcriptional RNA processing via interaction with CHD8. {ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:22570490, ECO:0000269|PubMed:25623890, ECO:0000269|PubMed:26051023, ECO:0000269|PubMed:2687284, ECO:0000269|PubMed:33174841, ECO:0000269|PubMed:36537238}. |
| P15814 | IGLL1 | S76 | ochoa | Immunoglobulin lambda-like polypeptide 1 (CD179 antigen-like family member B) (Ig lambda-5) (Immunoglobulin omega polypeptide) (Immunoglobulin-related protein 14.1) (CD antigen CD179b) | Critical for B-cell development. {ECO:0000269|PubMed:9419212}. |
| P15923 | TCF3 | S156 | ochoa | Transcription factor E2-alpha (Class B basic helix-loop-helix protein 21) (bHLHb21) (Immunoglobulin enhancer-binding factor E12/E47) (Immunoglobulin transcription factor 1) (Kappa-E2-binding factor) (Transcription factor 3) (TCF-3) (Transcription factor ITF-1) | Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition (By similarity). Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation (By similarity). Together with TCF15, required for the mesenchymal to epithelial transition (By similarity). Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (By similarity). {ECO:0000250|UniProtKB:P15806, ECO:0000269|PubMed:2493990}.; FUNCTION: [Isoform E47]: Facilitates ATOH7 binding to DNA at the consensus sequence 5'-CAGGTG-3', and positively regulates transcriptional activity. {ECO:0000269|PubMed:31696227}. |
| P16066 | NPR1 | S538 | psp | Atrial natriuretic peptide receptor 1 (EC 4.6.1.2) (Atrial natriuretic peptide receptor type A) (ANP-A) (ANPR-A) (NPR-A) (Guanylate cyclase A) (GC-A) | Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis (PubMed:39543315). Plays an essential role in the regulation of endothelial cell senescence and vascular aging (PubMed:36016499). Upon activation by ANP or BNP, stimulates the production of cyclic guanosine monophosphate (cGMP) that promotes vascular tone and volume homeostasis by activation of protein kinase cGMP-dependent 1/PRKG1 and subsequently PRKAA1, thereby controlling blood pressure and maintaining cardiovascular homeostasis (PubMed:36016499). {ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:36016499, ECO:0000269|PubMed:39543315}. |
| P17252 | PRKCA | S120 | ochoa | Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}. |
| P17535 | JUND | S43 | ochoa | Transcription factor JunD (Transcription factor AP-1 subunit JunD) | Transcription factor binding AP-1 sites (PubMed:9989505). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to an AP-1 consensus sequence 3'-TGA[GC]TCA-5' and enhancing their transcriptional activity (PubMed:28981703, PubMed:9989505). {ECO:0000269|PubMed:28981703, ECO:0000269|PubMed:9989505}. |
| P17858 | PFKL | S377 | ochoa | ATP-dependent 6-phosphofructokinase, liver type (ATP-PFK) (PFK-L) (EC 2.7.1.11) (6-phosphofructokinase type B) (Phosphofructo-1-kinase isozyme B) (PFK-B) (Phosphohexokinase) | Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (By similarity). {ECO:0000250|UniProtKB:P12382, ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}. |
| P17948 | FLT1 | S1207 | ochoa | Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275). {ECO:0000250|UniProtKB:P35969, ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537, ECO:0000269|Ref.11}.; FUNCTION: [Isoform 1]: Phosphorylates PLCG. {ECO:0000269|PubMed:9299537}.; FUNCTION: [Isoform 2]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 3]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 4]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:20512933}. |
| P18583 | SON | S1651 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P19793 | RXRA | S27 | psp | Retinoic acid receptor RXR-alpha (Nuclear receptor subfamily 2 group B member 1) (Retinoid X receptor alpha) | Receptor for retinoic acid that acts as a transcription factor (PubMed:10874028, PubMed:11162439, PubMed:11915042, PubMed:37478846). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:16107141, PubMed:17761950, PubMed:18800767, PubMed:19167885, PubMed:28167758, PubMed:37478846). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:10195690, PubMed:11162439, PubMed:11915042, PubMed:17761950, PubMed:28167758). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:1310260). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:20215566). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (PubMed:20215566, PubMed:37478846, PubMed:9267036). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:10195690, PubMed:11915042, PubMed:28167758, PubMed:29021580). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (PubMed:29021580). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (PubMed:10195690). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). Acts as an enhancer of RARA binding to RARE DNA element (PubMed:28167758). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (PubMed:12145331, PubMed:15509776). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (PubMed:30216632). {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:10874028, ECO:0000269|PubMed:11162439, ECO:0000269|PubMed:11915042, ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:1310260, ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:16107141, ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:18800767, ECO:0000269|PubMed:19167885, ECO:0000269|PubMed:20215566, ECO:0000269|PubMed:25417649, ECO:0000269|PubMed:26463675, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:29021580, ECO:0000269|PubMed:30216632, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9267036}. |
| P20309 | CHRM3 | S286 | ochoa | Muscarinic acetylcholine receptor M3 | The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. {ECO:0000269|PubMed:7565628}. |
| P20340 | RAB6A | S117 | ochoa | Ras-related protein Rab-6A (Rab-6) (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:25962623). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:25962623). RAB6A acts as a regulator of COPI-independent retrograde transport from the Golgi apparatus towards the endoplasmic reticulum (ER) (PubMed:25962623). Has a low GTPase activity (PubMed:25962623). Recruits VPS13B to the Golgi membrane (PubMed:25492866). Plays a role in neuron projection development (Probable). {ECO:0000269|PubMed:25492866, ECO:0000269|PubMed:25962623, ECO:0000305|PubMed:25492866}. |
| P20929 | NEB | S437 | ochoa | Nebulin | This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin. |
| P21333 | FLNA | S1409 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | S2292 | ochoa|psp | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | S2494 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P22102 | GART | S796 | ochoa | Trifunctional purine biosynthetic protein adenosine-3 [Includes: Phosphoribosylamine--glycine ligase (EC 6.3.4.13) (Glycinamide ribonucleotide synthetase) (GARS) (Phosphoribosylglycinamide synthetase); Phosphoribosylformylglycinamidine cyclo-ligase (EC 6.3.3.1) (AIR synthase) (AIRS) (Phosphoribosyl-aminoimidazole synthetase); Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) (5'-phosphoribosylglycinamide transformylase) (GAR transformylase) (GART)] | Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway. {ECO:0000305|PubMed:12450384, ECO:0000305|PubMed:12755606, ECO:0000305|PubMed:20631005, ECO:0000305|PubMed:2183217}. |
| P22234 | PAICS | S274 | ochoa | Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) [Includes: Phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21) (AIR carboxylase) (AIRC); Phosphoribosylaminoimidazole succinocarboxamide synthetase (EC 6.3.2.6) (SAICAR synthetase)] | Bifunctional phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase catalyzing two reactions of the de novo purine biosynthetic pathway. {ECO:0000269|PubMed:17224163, ECO:0000269|PubMed:2183217, ECO:0000269|PubMed:31600779}. |
| P22466 | GAL | S76 | ochoa | Galanin peptides [Cleaved into: Galanin; Galanin message-associated peptide (GMAP)] | Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion. {ECO:0000269|PubMed:1370155, ECO:0000269|PubMed:1722333, ECO:0000269|PubMed:25691535}. |
| P22694 | PRKACB | S54 | ochoa | cAMP-dependent protein kinase catalytic subunit beta (PKA C-beta) (EC 2.7.11.11) | Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs (PubMed:12420224, PubMed:21423175, PubMed:31112131). PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux (PubMed:12420224, PubMed:21423175). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142, ECO:0000269|PubMed:31112131}. |
| P22695 | UQCRC2 | S303 | ochoa | Cytochrome b-c1 complex subunit 2, mitochondrial (Complex III subunit 2) (Core protein II) (Ubiquinol-cytochrome-c reductase complex core protein 2) | Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties (By similarity). May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (Probable). {ECO:0000250|UniProtKB:P07257, ECO:0000250|UniProtKB:P23004, ECO:0000305|PubMed:29243944}. |
| P23327 | HRC | S457 | ochoa | Sarcoplasmic reticulum histidine-rich calcium-binding protein | May play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle. |
| P23588 | EIF4B | S263 | ochoa | Eukaryotic translation initiation factor 4B (eIF-4B) | Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F. |
| P24534 | EEF1B2 | S174 | ochoa | Elongation factor 1-beta (EF-1-beta) (eEF-1B alpha) | Catalytic subunit of the guanine nucleotide exchange factor (GEF) (eEF1B subcomplex) of the eukaryotic elongation factor 1 complex (eEF1) (By similarity). Stimulates the exchange of GDP for GTP on elongation factor 1A (eEF1A), probably by displacing GDP from the nucleotide binding pocket in eEF1A (By similarity). {ECO:0000250|UniProtKB:P32471}. |
| P25705 | ATP5F1A | S236 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P25705 | ATP5F1A | S451 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P25963 | NFKBIA | S63 | psp | NF-kappa-B inhibitor alpha (I-kappa-B-alpha) (IkB-alpha) (IkappaBalpha) (Major histocompatibility complex enhancer-binding protein MAD3) | Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:36651806, PubMed:7479976). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7479976, PubMed:7628694, PubMed:7796813, PubMed:7878466). {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:36651806, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466}. |
| P26639 | TARS1 | S596 | ochoa | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P26641 | EEF1G | S406 | ochoa | Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) | Probably plays a role in anchoring the complex to other cellular components. |
| P27816 | MAP4 | S941 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P29350 | PTPN6 | S26 | ochoa | Tyrosine-protein phosphatase non-receptor type 6 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase) (Protein-tyrosine phosphatase 1C) (PTP-1C) (Protein-tyrosine phosphatase SHP-1) (SH-PTP1) | Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities (PubMed:21258366, PubMed:9733788). When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events (PubMed:11907092, PubMed:14739280, PubMed:37932456, PubMed:38166031). Modulates the signaling of several cytokine receptors including IL-4 receptor (PubMed:9065461). Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling (PubMed:34811497, PubMed:38532423). Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Also acts as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A (PubMed:37595871). {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:11266449, ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:14739280, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:29925997, ECO:0000269|PubMed:34811497, ECO:0000269|PubMed:37595871, ECO:0000269|PubMed:37932456, ECO:0000269|PubMed:38166031, ECO:0000269|PubMed:38532423, ECO:0000269|PubMed:9065461, ECO:0000269|PubMed:9733788}. |
| P29353 | SHC1 | S139 | ochoa|psp | SHC-transforming protein 1 (SHC-transforming protein 3) (SHC-transforming protein A) (Src homology 2 domain-containing-transforming protein C1) (SH2 domain protein C1) | Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. {ECO:0000250, ECO:0000269|PubMed:14665640}. |
| P30519 | HMOX2 | S280 | ochoa | Heme oxygenase 2 (HO-2) (EC 1.14.14.18) [Cleaved into: Heme oxygenase 2 soluble form] | [Heme oxygenase 2]: Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron. {ECO:0000269|PubMed:1575508, ECO:0000269|PubMed:7890772}.; FUNCTION: [Heme oxygenase 2 soluble form]: Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron. {ECO:0000269|PubMed:7890772}. |
| P31323 | PRKAR2B | S220 | ochoa | cAMP-dependent protein kinase type II-beta regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P31629 | HIVEP2 | S41 | ochoa | Transcription factor HIVEP2 (Human immunodeficiency virus type I enhancer-binding protein 2) (HIV-EP2) (MHC-binding protein 2) (MBP-2) | This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon-beta genes. It may act in T-cell activation. |
| P31943 | HNRNPH1 | S281 | ochoa | Heterogeneous nuclear ribonucleoprotein H (hnRNP H) [Cleaved into: Heterogeneous nuclear ribonucleoprotein H, N-terminally processed] | This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG). {ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:16946708}. |
| P35125 | USP6 | S1214 | ochoa | Ubiquitin carboxyl-terminal hydrolase 6 (EC 3.4.19.12) (Deubiquitinating enzyme 6) (Proto-oncogene TRE-2) (RN-tre) (Ubiquitin thioesterase 6) (Ubiquitin-specific-processing protease 6) | Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation. May act as a GTPase-activating protein for RAB3A (PubMed:19077034). {ECO:0000269|PubMed:15509780, ECO:0000269|PubMed:16127172, ECO:0000269|PubMed:19077034, ECO:0000269|PubMed:20418905}. |
| P35269 | GTF2F1 | S396 | ochoa | General transcription factor IIF subunit 1 (General transcription factor IIF 74 kDa subunit) (Transcription initiation factor IIF subunit alpha) (TFIIF-alpha) (Transcription initiation factor RAP74) | TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation. {ECO:0000269|PubMed:10428810}. |
| P35348 | ADRA1A | S407 | psp | Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P35367 | HRH1 | S317 | ochoa | Histamine H1 receptor (H1-R) (H1R) (HH1R) | G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity). {ECO:0000250|UniProtKB:P70174, ECO:0000269|PubMed:33828102, ECO:0000269|PubMed:8280179}. |
| P35555 | FBN1 | S2563 | ochoa | Fibrillin-1 [Cleaved into: Asprosin] | [Fibrillin-1]: Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:15062093, PubMed:1860873). Fibrillin-1-containing microfibrils provide long-term force bearing structural support (PubMed:27026396). In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin (PubMed:27026396). In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus where they provide tensile strength and have anchoring roles (PubMed:27026396). Fibrillin-1 also plays a key role in tissue homeostasis through specific interactions with growth factors, such as the bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and latent transforming growth factor-beta-binding proteins (LTBPs), cell-surface integrins and other extracellular matrix protein and proteoglycan components (PubMed:27026396). Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (By similarity). Negatively regulates osteoclastogenesis by binding and sequestering an osteoclast differentiation and activation factor TNFSF11 (PubMed:24039232). This leads to disruption of TNFSF11-induced Ca(2+) signaling and impairment of TNFSF11-mediated nuclear translocation and activation of transcription factor NFATC1 which regulates genes important for osteoclast differentiation and function (PubMed:24039232). Mediates cell adhesion via its binding to cell surface receptors integrins ITGAV:ITGB3 and ITGA5:ITGB1 (PubMed:12807887, PubMed:17158881). Binds heparin and this interaction has an important role in the assembly of microfibrils (PubMed:11461921). {ECO:0000250|UniProtKB:Q61554, ECO:0000269|PubMed:11461921, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:15062093, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:1860873, ECO:0000269|PubMed:24039232, ECO:0000303|PubMed:27026396}.; FUNCTION: [Asprosin]: Adipokine secreted by white adipose tissue that plays an important regulatory role in the glucose metabolism of liver, muscle and pancreas (PubMed:27087445, PubMed:30853600). Hormone that targets the liver in response to fasting to increase plasma glucose levels (PubMed:27087445). Binds the olfactory receptor OR4M1 at the surface of hepatocytes and promotes hepatocyte glucose release by activating the protein kinase A activity in the liver, resulting in rapid glucose release into the circulation (PubMed:27087445, PubMed:31230984). May act as a regulator of adaptive thermogenesis by inhibiting browning and energy consumption, while increasing lipid deposition in white adipose tissue (By similarity). Also acts as an orexigenic hormone that increases appetite: crosses the blood brain barrier and exerts effects on the hypothalamus (By similarity). In the arcuate nucleus of the hypothalamus, asprosin directly activates orexigenic AgRP neurons and indirectly inhibits anorexigenic POMC neurons, resulting in appetite stimulation (By similarity). Activates orexigenic AgRP neurons via binding to the olfactory receptor OR4M1 (By similarity). May also play a role in sperm motility in testis via interaction with OR4M1 receptor (By similarity). {ECO:0000250|UniProtKB:Q61554, ECO:0000269|PubMed:27087445, ECO:0000269|PubMed:30853600, ECO:0000269|PubMed:31230984}. |
| P35580 | MYH10 | S641 | ochoa | Myosin-10 (Cellular myosin heavy chain, type B) (Myosin heavy chain 10) (Myosin heavy chain, non-muscle IIb) (Non-muscle myosin heavy chain B) (NMMHC-B) (Non-muscle myosin heavy chain IIb) (NMMHC II-b) (NMMHC-IIB) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the central part but not the margins of spreading cells), and lamellipodial extension; this function is mechanically antagonized by MYH9. {ECO:0000269|PubMed:20052411, ECO:0000269|PubMed:20603131}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000305|PubMed:25428876, ECO:0000305|PubMed:39048823}. |
| P37059 | HSD17B2 | S234 | ochoa | 17-beta-hydroxysteroid dehydrogenase type 2 (17-beta-HSD 2) (20 alpha-hydroxysteroid dehydrogenase) (20-alpha-HSD) (E2DH) (Estradiol 17-beta-dehydrogenase 2) (EC 1.1.1.62) (Microsomal 17-beta-hydroxysteroid dehydrogenase) (Short chain dehydrogenase/reductase family 9C member 2) (Testosterone 17-beta-dehydrogenase) (EC 1.1.1.239) | Catalyzes the NAD-dependent oxidation of the highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulates the biological potency of these steroids. Oxidizes estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity. {ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569, ECO:0000269|PubMed:8099587}. |
| P37837 | TALDO1 | S75 | ochoa | Transaldolase (EC 2.2.1.2) | Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway. Catalyzes the reversible conversion of sedheptulose-7-phosphate and D-glyceraldehyde 3-phosphate into erythrose-4-phosphate and beta-D-fructose 6-phosphate (PubMed:18687684, PubMed:8955144). Not only acts as a pentose phosphate pathway enzyme, but also affects other metabolite pathways by altering its subcellular localization between the nucleus and the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q93092, ECO:0000269|PubMed:18687684, ECO:0000269|PubMed:8955144}. |
| P38159 | RBMX | S280 | ochoa | RNA-binding motif protein, X chromosome (Glycoprotein p43) (Heterogeneous nuclear ribonucleoprotein G) (hnRNP G) [Cleaved into: RNA-binding motif protein, X chromosome, N-terminally processed] | RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Also plays a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:12761049, ECO:0000269|PubMed:16707624, ECO:0000269|PubMed:18445477, ECO:0000269|PubMed:18541147, ECO:0000269|PubMed:19282290, ECO:0000269|PubMed:21327109}. |
| P38398 | BRCA1 | S395 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P39656 | DDOST | S143 | ochoa | Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit (DDOST 48 kDa subunit) (Oligosaccharyl transferase 48 kDa subunit) | Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (PubMed:31831667). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes (PubMed:22467853). {ECO:0000250|UniProtKB:Q05052, ECO:0000269|PubMed:22467853, ECO:0000269|PubMed:31831667}. |
| P39748 | FEN1 | S335 | ochoa | Flap endonuclease 1 (FEN-1) (EC 3.1.-.-) (DNase IV) (Flap structure-specific endonuclease 1) (Maturation factor 1) (MF1) (hFEN-1) | Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}. |
| P40763 | STAT3 | S701 | ochoa | Signal transducer and activator of transcription 3 (Acute-phase response factor) | Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18242580, PubMed:18782771, PubMed:22306293, PubMed:23084476, PubMed:28262505, PubMed:32929201, PubMed:38404237). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18782771, PubMed:28262505, PubMed:32929201). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acetylation promotes its transcription activity and cell differentiation while deacetylation and oxidation of lysine residues by LOXL3 inhibits differentiation (PubMed:28065600, PubMed:28262505). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC3 and NFATC4, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:P42227, ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:12359225, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:16285960, ECO:0000269|PubMed:17344214, ECO:0000269|PubMed:18242580, ECO:0000269|PubMed:18782771, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:28065600, ECO:0000269|PubMed:28262505, ECO:0000269|PubMed:32929201, ECO:0000269|PubMed:38404237}. |
| P41250 | GARS1 | S653 | ochoa | Glycine--tRNA ligase (EC 6.1.1.14) (Diadenosine tetraphosphate synthetase) (Ap4A synthetase) (EC 2.7.7.-) (Glycyl-tRNA synthetase) (GlyRS) (Glycyl-tRNA synthetase 1) | Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:24898252, PubMed:28675565). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017). {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:19710017, ECO:0000269|PubMed:24898252, ECO:0000269|PubMed:28675565}. |
| P41743 | PRKCI | S458 | ochoa | Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) | Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}. |
| P42685 | FRK | S92 | ochoa | Tyrosine-protein kinase FRK (EC 2.7.10.2) (FYN-related kinase) (Nuclear tyrosine protein kinase RAK) (Protein-tyrosine kinase 5) | Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor. {ECO:0000269|PubMed:19345329}. |
| P43004 | SLC1A2 | S25 | ochoa | Excitatory amino acid transporter 2 (Glutamate/aspartate transporter II) (Sodium-dependent glutamate/aspartate transporter 2) (Solute carrier family 1 member 2) | Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:14506254, PubMed:15265858, PubMed:26690923, PubMed:7521911). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:14506254). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:14506254). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (By similarity). {ECO:0000250|UniProtKB:P43006, ECO:0000269|PubMed:15265858, ECO:0000269|PubMed:26690923, ECO:0000269|PubMed:7521911}. |
| P43897 | TSFM | S270 | ochoa | Elongation factor Ts, mitochondrial (EF-Ts) (EF-TsMt) | Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome. {ECO:0000255|HAMAP-Rule:MF_03135, ECO:0000269|PubMed:27677415}. |
| P46821 | MAP1B | S339 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P47736 | RAP1GAP | S495 | ochoa | Rap1 GTPase-activating protein 1 (Rap1GAP) (Rap1GAP1) | GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. {ECO:0000269|PubMed:15141215}. |
| P48742 | LHX1 | S168 | ochoa | LIM/homeobox protein Lhx1 (LIM homeobox protein 1) (Homeobox protein Lim-1) (hLim-1) | Potential transcription factor. May play a role in early mesoderm formation and later in lateral mesoderm differentiation and neurogenesis. {ECO:0000269|PubMed:9212161}. |
| P49327 | FASN | S2253 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49790 | NUP153 | S562 | ochoa | Nuclear pore complex protein Nup153 (153 kDa nucleoporin) (Nucleoporin Nup153) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC). {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22253824}.; FUNCTION: (Microbial infection) Interacts with HIV-1 caspid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro). {ECO:0000269|PubMed:23523133, ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:29997211}.; FUNCTION: (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro). {ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:31913756}. |
| P49792 | RANBP2 | S1260 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S2518 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49815 | TSC2 | S1002 | ochoa | Tuberin (Tuberous sclerosis 2 protein) | Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:33436626, ECO:0000269|PubMed:35772404}. |
| P49841 | GSK3B | S25 | ochoa | Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1) | Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:11430833, PubMed:12554650, PubMed:14690523, PubMed:16484495, PubMed:1846781, PubMed:20937854, PubMed:9072970). Requires primed phosphorylation of the majority of its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:8397507). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:8397507). Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (PubMed:14690523). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (By similarity). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed:22514281). Phosphorylates SNAI1, leading to its ubiquitination and proteasomal degradation (PubMed:15448698, PubMed:15647282, PubMed:25827072, PubMed:29059170). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (By similarity). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110). Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2 complex component RICTOR at 'Ser-1235' in response to endoplasmic stress, inhibiting mTORC2 (PubMed:21343617). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (By similarity). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20067585, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:29059170, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}. |
| P49848 | TAF6 | S602 | ochoa | Transcription initiation factor TFIID subunit 6 (RNA polymerase II TBP-associated factor subunit E) (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII70) (Transcription initiation factor TFIID 80 kDa subunit) (TAF(II)80) (TAFII-80) (TAFII80) | The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (PubMed:33795473). TAF6 homodimer connects TFIID modules, forming a rigid core (PubMed:33795473). {ECO:0000269|PubMed:33795473}.; FUNCTION: [Isoform 4]: Transcriptional regulator which acts primarily as a positive regulator of transcription (PubMed:20096117, PubMed:29358700). Recruited to the promoters of a number of genes including GADD45A and CDKN1A/p21, leading to transcriptional up-regulation and subsequent induction of apoptosis (PubMed:11583621). Also up-regulates expression of other genes including GCNA/ACRC, HES1 and IFFO1 (PubMed:18628956). In contrast, down-regulates transcription of MDM2 (PubMed:11583621). Acts as a transcriptional coactivator to enhance transcription of TP53/p53-responsive genes such as DUSP1 (PubMed:20096117). Can also activate transcription and apoptosis independently of TP53 (PubMed:18628956). Drives apoptosis via the intrinsic apoptotic pathway by up-regulating apoptosis effectors such as BCL2L11/BIM and PMAIP1/NOXA (PubMed:29358700). {ECO:0000269|PubMed:11583621, ECO:0000269|PubMed:18628956, ECO:0000269|PubMed:20096117, ECO:0000269|PubMed:29358700}. |
| P50851 | LRBA | S971 | ochoa | Lipopolysaccharide-responsive and beige-like anchor protein (Beige-like protein) (CDC4-like protein) | Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). {ECO:0000250|UniProtKB:Q9ESE1, ECO:0000269|PubMed:33773106}. |
| P50990 | CCT8 | S380 | ochoa | T-complex protein 1 subunit theta (TCP-1-theta) (EC 3.6.1.-) (CCT-theta) (Chaperonin containing T-complex polypeptide 1 subunit 8) (Renal carcinoma antigen NY-REN-15) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P50993 | ATP1A2 | S464 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-2) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P51531 | SMARCA2 | S698 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SAMRCA2) (EC 3.6.4.-) (BRG1-associated factor 190B) (BAF190B) (Probable global transcription activator SNF2L2) (Protein brahma homolog) (hBRM) (SNF2-alpha) | ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:15075294, PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6DIC0, ECO:0000269|PubMed:15075294, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P51668 | UBE2D1 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D1 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D1) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D1) (Stimulator of Fe transport) (SFT) (UBC4/5 homolog) (UbcH5) (Ubiquitin carrier protein D1) (Ubiquitin-conjugating enzyme E2(17)KB 1) (Ubiquitin-conjugating enzyme E2-17 kDa 1) (Ubiquitin-protein ligase D1) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:22496338). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:20061386). Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1 (PubMed:18042044, PubMed:18359941). Ubiquitinates STUB1-associated HSP90AB1 in vitro (PubMed:18042044). Lacks inherent specificity for any particular lysine residue of ubiquitin (PubMed:18042044). Essential for viral activation of IRF3 (PubMed:19854139). Mediates polyubiquitination of CYP3A4 (PubMed:19103148). {ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18359941, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338}. |
| P52179 | MYOM1 | S1497 | ochoa | Myomesin-1 (190 kDa connectin-associated protein) (190 kDa titin-associated protein) (Myomesin family member 1) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P52272 | HNRNPM | S446 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52789 | HK2 | S415 | ochoa | Hexokinase-2 (EC 2.7.1.1) (Hexokinase type II) (HK II) (Hexokinase-B) (Muscle form hexokinase) | Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively) (PubMed:23185017, PubMed:26985301, PubMed:29298880). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:29298880). Plays a key role in maintaining the integrity of the outer mitochondrial membrane by preventing the release of apoptogenic molecules from the intermembrane space and subsequent apoptosis (PubMed:18350175). {ECO:0000269|PubMed:18350175, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:26985301, ECO:0000269|PubMed:29298880}. |
| P52799 | EFNB2 | S284 | ochoa | Ephrin-B2 (EPH-related receptor tyrosine kinase ligand 5) (LERK-5) (HTK ligand) (HTK-L) | Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons. {ECO:0000269|PubMed:12734395}.; FUNCTION: (Microbial infection) Acts as a receptor for Hendra virus and Nipah virus. {ECO:0000269|PubMed:15998730, ECO:0000269|PubMed:16007075, ECO:0000269|PubMed:16477309, ECO:0000269|PubMed:17376907}. |
| P53004 | BLVRA | S21 | psp | Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) | Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}. |
| P53355 | DAPK1 | S366 | ochoa | Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1) | Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing. |
| P53814 | SMTN | S734 | ochoa | Smoothelin | Structural protein of the cytoskeleton. |
| P54198 | HIRA | S111 | ochoa | Protein HIRA (TUP1-like enhancer of split protein 1) | Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:12370293, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527}. |
| P55011 | SLC12A2 | S132 | ochoa | Solute carrier family 12 member 2 (Basolateral Na-K-Cl symporter) (Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2) (BSC2) (Na-K-2Cl cotransporter 1) (hNKCC1) | Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:16669787, PubMed:32081947, PubMed:32294086, PubMed:33597714, PubMed:35585053, PubMed:36239040, PubMed:36306358, PubMed:7629105). Plays a vital role in the regulation of ionic balance and cell volume (PubMed:16669787, PubMed:32081947, PubMed:32294086, PubMed:7629105). {ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:32081947, ECO:0000269|PubMed:32294086, ECO:0000269|PubMed:33597714, ECO:0000269|PubMed:35585053, ECO:0000269|PubMed:36239040, ECO:0000269|PubMed:36306358, ECO:0000269|PubMed:7629105}. |
| P55735 | SEC13 | S166 | ochoa | Protein SEC13 homolog (GATOR2 complex protein SEC13) (SEC13-like protein 1) (SEC13-related protein) | Functions as a component of the nuclear pore complex (NPC) and the COPII coat (PubMed:8972206). At the endoplasmic reticulum, SEC13 is involved in the biogenesis of COPII-coated vesicles (PubMed:8972206). Required for the exit of adipsin (CFD/ADN), an adipocyte-secreted protein from the endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q9D1M0, ECO:0000269|PubMed:8972206}.; FUNCTION: As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:25457612, PubMed:27487210, PubMed:35831510, PubMed:36528027). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:27487210, PubMed:35831510, PubMed:36528027). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25457612, PubMed:26972053, PubMed:27487210). Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex (PubMed:35831510). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26972053, ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027}. |
| P55795 | HNRNPH2 | S281 | ochoa | Heterogeneous nuclear ribonucleoprotein H2 (hnRNP H2) (FTP-3) (Heterogeneous nuclear ribonucleoprotein H') (hnRNP H') [Cleaved into: Heterogeneous nuclear ribonucleoprotein H2, N-terminally processed] | This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Binds poly(RG). |
| P56470 | LGALS4 | S229 | ochoa | Galectin-4 (Gal-4) (Antigen NY-CO-27) (L-36 lactose-binding protein) (L36LBP) (Lactose-binding lectin 4) | Galectin that binds lactose and a related range of sugars. May be involved in the assembly of adherens junctions. |
| P56470 | LGALS4 | S258 | ochoa | Galectin-4 (Gal-4) (Antigen NY-CO-27) (L-36 lactose-binding protein) (L36LBP) (Lactose-binding lectin 4) | Galectin that binds lactose and a related range of sugars. May be involved in the assembly of adherens junctions. |
| P60842 | EIF4A1 | S322 | ochoa | Eukaryotic initiation factor 4A-I (eIF-4A-I) (eIF4A-I) (EC 3.6.4.13) (ATP-dependent RNA helicase eIF4A-1) | ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome (PubMed:20156963). In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. As a result, promotes cell proliferation and growth (PubMed:20156963). {ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291, ECO:0000269|PubMed:20156963}. |
| P61077 | UBE2D3 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D3 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D3) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D3) (Ubiquitin carrier protein D3) (Ubiquitin-conjugating enzyme E2(17)KB 3) (Ubiquitin-conjugating enzyme E2-17 kDa 3) (Ubiquitin-protein ligase D3) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592, PubMed:28322253). In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592). Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:20347421). Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin (PubMed:10329681). Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin (PubMed:10329681). Also acts as an initiator E2, in conjunction with RNF8, for the priming of PCNA (PubMed:18948756). Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase (PubMed:18948756). Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair (PubMed:16628214). Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus (PubMed:18515077). In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53 (PubMed:12646252, PubMed:15280377). In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes (PubMed:18508924). In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (PubMed:11743028). Together with RNF135, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175). Together with ZNF598, catalyzes ubiquitination of 40S ribosomal proteins in response to ribosome collisions (PubMed:28685749). In cooperation with the GATOR2 complex, catalyzes 'Lys-6'-linked ubiquitination of NPRL2 (PubMed:36528027). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:11743028, ECO:0000269|PubMed:12646252, ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:15496420, ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:18284575, ECO:0000269|PubMed:18508924, ECO:0000269|PubMed:18515077, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:28322253, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:28685749, ECO:0000269|PubMed:36528027}. |
| P61160 | ACTR2 | S307 | ochoa | Actin-related protein 2 (Actin-like protein 2) | ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9000076). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9000076). Seems to contact the pointed end of the daughter actin filament (PubMed:9000076). In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation (PubMed:29058690). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:17220302, PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:17220302, ECO:0000269|PubMed:29058690, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9000076}. |
| P61326 | MAGOH | S106 | ochoa | Protein mago nashi homolog | Required for pre-mRNA splicing as component of the spliceosome (PubMed:11991638). Plays a redundant role with MAGOHB as core component of the exon junction complex (EJC) and in the nonsense-mediated decay (NMD) pathway (PubMed:23917022). The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S pre-initiation complex. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly. {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12730685, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:23917022}. |
| P61421 | ATP6V0D1 | S283 | ochoa | V-type proton ATPase subunit d 1 (V-ATPase subunit d 1) (32 kDa accessory protein) (V-ATPase 40 kDa accessory protein) (V-ATPase AC39 subunit) (p39) (Vacuolar proton pump subunit d 1) | Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:28296633, PubMed:30374053, PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:30374053). May play a role in coupling of proton transport and ATP hydrolysis (By similarity). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (By similarity). {ECO:0000250|UniProtKB:P51863, ECO:0000250|UniProtKB:Q6PGV1, ECO:0000269|PubMed:28296633, ECO:0000269|PubMed:30374053, ECO:0000269|PubMed:33065002}. |
| P61978 | HNRNPK | S430 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P62318 | SNRPD3 | S66 | ochoa | Small nuclear ribonucleoprotein Sm D3 (Sm-D3) (snRNP core protein D3) | Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:25555158, PubMed:26912367, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:28781166). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (By similarity). {ECO:0000250|UniProtKB:P62320, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:19325628, ECO:0000269|PubMed:25555158, ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932}. |
| P62837 | UBE2D2 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D2 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D2) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D2) (Ubiquitin carrier protein D2) (Ubiquitin-conjugating enzyme E2(17)KB 2) (Ubiquitin-conjugating enzyme E2-17 kDa 2) (Ubiquitin-protein ligase D2) (p53-regulated ubiquitin-conjugating enzyme 1) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:10329681, PubMed:18042044, PubMed:18703417, PubMed:20061386, PubMed:20403326, PubMed:20525694, PubMed:26475854, PubMed:28322253). Catalyzes 'Lys-48'-linked polyubiquitination (PubMed:10329681, PubMed:18042044, PubMed:18359941, PubMed:18703417, PubMed:20061386, PubMed:20403326, PubMed:20525694, PubMed:26475854). Mediates the selective degradation of short-lived and abnormal proteins (PubMed:10329681, PubMed:18042044, PubMed:18359941, PubMed:18703417, PubMed:20061386, PubMed:20403326, PubMed:20525694, PubMed:26475854). Functions in the E6/E6-AP-induced ubiquitination of p53/TP53 (PubMed:15280377). Mediates ubiquitination of PEX5 and SQSTM1 and autoubiquitination of STUB1 and TRAF6 (PubMed:18359941, PubMed:28322253). Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by RIGI in response to viral infection (PubMed:18703417, PubMed:20403326). Essential for viral activation of IRF3 (PubMed:19854139). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18359941, ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20403326, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:26475854, ECO:0000269|PubMed:28322253}. |
| P62937 | PPIA | S51 | ochoa | Peptidyl-prolyl cis-trans isomerase A (PPIase A) (EC 5.2.1.8) (Cyclophilin A) (Cyclosporin A-binding protein) (Rotamase A) [Cleaved into: Peptidyl-prolyl cis-trans isomerase A, N-terminally processed] | Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.; FUNCTION: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.; FUNCTION: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}. |
| P62995 | TRA2B | S215 | ochoa | Transformer-2 protein homolog beta (TRA-2 beta) (TRA2-beta) (hTRA2-beta) (Splicing factor, arginine/serine-rich 10) (Transformer-2 protein homolog B) | Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. Can either activate or suppress exon inclusion. Acts additively with RBMX to promote exon 7 inclusion of the survival motor neuron SMN2. Activates the splicing of MAPT/Tau exon 10. Alters pre-mRNA splicing patterns by antagonizing the effects of splicing regulators, like RBMX. Binds to the AG-rich SE2 domain in the SMN exon 7 RNA. Binds to pre-mRNA. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:12761049, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:9546399}. |
| P67809 | YBX1 | S174 | ochoa|psp | Y-box-binding protein 1 (YB-1) (CCAAT-binding transcription factor I subunit A) (CBF-A) (DNA-binding protein B) (DBPB) (Enhancer factor I subunit A) (EFI-A) (Nuclease-sensitive element-binding protein 1) (Y-box transcription factor) | DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:10817758, PubMed:11698476, PubMed:14718551, PubMed:18809583, PubMed:31358969, PubMed:8188694). Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (PubMed:19561594, PubMed:31358969). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (PubMed:10817758, PubMed:11698476, PubMed:31358969). Component of the CRD-mediated complex that promotes MYC mRNA stability (PubMed:19029303). Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs (PubMed:27559612, PubMed:29073095). Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (PubMed:28341602, PubMed:29073095). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (PubMed:29712925). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (PubMed:12604611). Binds to TSC22D1 transcripts, thereby inhibiting their translation and negatively regulating TGF-beta-mediated transcription of COL1A2 (By similarity). Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7' (PubMed:18809583). Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (PubMed:18809583, PubMed:8188694). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (PubMed:14718551). Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (PubMed:14718551). The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (PubMed:19483673). {ECO:0000250|UniProtKB:P62960, ECO:0000250|UniProtKB:Q28618, ECO:0000269|PubMed:10817758, ECO:0000269|PubMed:11698476, ECO:0000269|PubMed:12604611, ECO:0000269|PubMed:14718551, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19483673, ECO:0000269|PubMed:19561594, ECO:0000269|PubMed:27559612, ECO:0000269|PubMed:28341602, ECO:0000269|PubMed:29073095, ECO:0000269|PubMed:29712925, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:8188694}. |
| P68371 | TUBB4B | S278 | ochoa | Tubulin beta-4B chain (Tubulin beta-2 chain) (Tubulin beta-2C chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P85037 | FOXK1 | S377 | ochoa | Forkhead box protein K1 (Myocyte nuclear factor) (MNF) | Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:17670796). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity). Represses myogenic differentiation by inhibiting MEFC activity (By similarity). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK1-bound genes (PubMed:24634419, PubMed:30664650). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164, ECO:0000269|PubMed:30664650}. |
| Q00537 | CDK17 | S83 | ochoa | Cyclin-dependent kinase 17 (EC 2.7.11.22) (Cell division protein kinase 17) (PCTAIRE-motif protein kinase 2) (Serine/threonine-protein kinase PCTAIRE-2) | May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}. |
| Q00G26 | PLIN5 | S203 | ochoa | Perilipin-5 (Lipid storage droplet protein 5) | Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE (By similarity). {ECO:0000250, ECO:0000269|PubMed:17234449}. |
| Q01167 | FOXK2 | S330 | ochoa | Forkhead box protein K2 (G/T-mismatch specific binding protein) (nGTBP) (Interleukin enhancer-binding factor 1) | Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:22083952, PubMed:25451922). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK2-bound genes (PubMed:24634419, PubMed:30664650). {ECO:0000250|UniProtKB:Q3UCQ1, ECO:0000269|PubMed:1339390, ECO:0000269|PubMed:1909027, ECO:0000269|PubMed:20097901, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:30664650}. |
| Q01201 | RELB | S151 | ochoa | Transcription factor RelB (I-Rel) | NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function (PubMed:26385063). {ECO:0000269|PubMed:1732739, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:26385063, ECO:0000269|PubMed:7925301, ECO:0000269|PubMed:8441398}. |
| Q01995 | TAGLN | S181 | ochoa|psp | Transgelin (22 kDa actin-binding protein) (Protein WS3-10) (Smooth muscle protein 22-alpha) (SM22-alpha) | Actin cross-linking/gelling protein (By similarity). Involved in calcium interactions and contractile properties of the cell that may contribute to replicative senescence. {ECO:0000250}. |
| Q02952 | AKAP12 | S294 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q04206 | RELA | S45 | ochoa|psp | Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148}. |
| Q04206 | RELA | S238 | ochoa|psp | Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148}. |
| Q04637 | EIF4G1 | S1028 | ochoa | Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}. |
| Q04637 | EIF4G1 | S1077 | ochoa | Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}. |
| Q05397 | PTK2 | S843 | ochoa|psp | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| Q06418 | TYRO3 | S818 | ochoa | Tyrosine-protein kinase receptor TYRO3 (EC 2.7.10.1) (Tyrosine-protein kinase BYK) (Tyrosine-protein kinase DTK) (Tyrosine-protein kinase RSE) (Tyrosine-protein kinase SKY) (Tyrosine-protein kinase TIF) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:20546121}.; FUNCTION: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:22673088, ECO:0000269|PubMed:25277499}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:17005688}. |
| Q06830 | PRDX1 | S181 | ochoa | Peroxiredoxin-1 (EC 1.11.1.24) (Natural killer cell-enhancing factor A) (NKEF-A) (Proliferation-associated gene protein) (PAG) (Thioredoxin peroxidase 2) (Thioredoxin-dependent peroxide reductase 2) (Thioredoxin-dependent peroxiredoxin 1) | Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity). {ECO:0000250|UniProtKB:P0CB50, ECO:0000269|PubMed:9497357}. |
| Q07666 | KHDRBS1 | S202 | ochoa | KH domain-containing, RNA-binding, signal transduction-associated protein 1 (GAP-associated tyrosine phosphoprotein p62) (Src-associated in mitosis 68 kDa protein) (Sam68) (p21 Ras GTPase-activating protein-associated p62) (p68) | Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (PubMed:22253824). RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner (PubMed:26080397). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836, PubMed:20186123). Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity). {ECO:0000250|UniProtKB:Q60749, ECO:0000269|PubMed:15021911, ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20186123, ECO:0000269|PubMed:20610388, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:26758068}.; FUNCTION: Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase. {ECO:0000269|PubMed:9013542}. |
| Q08174 | PCDH1 | S1014 | ochoa | Protocadherin-1 (Cadherin-like protein 1) (Protocadherin-42) (PC42) | May be involved in cell-cell interaction processes and in cell adhesion. |
| Q09028 | RBBP4 | S110 | ochoa | Histone-binding protein RBBP4 (Chromatin assembly factor 1 subunit C) (CAF-1 subunit C) (Chromatin assembly factor I p48 subunit) (CAF-I 48 kDa subunit) (CAF-I p48) (Nucleosome-remodeling factor subunit RBAP48) (Retinoblastoma-binding protein 4) (RBBP-4) (Retinoblastoma-binding protein p48) | Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA (PubMed:10866654). Component of the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair (PubMed:8858152). Component of the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression (PubMed:9150135). Component of the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling (PubMed:16428440, PubMed:28977666, PubMed:39460621). Component of the PRC2 complex, which promotes repression of homeotic genes during development (PubMed:29499137, PubMed:31959557). Component of the NURF (nucleosome remodeling factor) complex (PubMed:14609955, PubMed:15310751). {ECO:0000269|PubMed:10866654, ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:15310751, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557, ECO:0000269|PubMed:39460621, ECO:0000269|PubMed:8858152, ECO:0000269|PubMed:9150135}. |
| Q09666 | AHNAK | S5400 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12815 | TROAP | S156 | ochoa | Tastin (Trophinin-assisting protein) (Trophinin-associated protein) | Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation. |
| Q12879 | GRIN2A | S929 | psp | Glutamate receptor ionotropic, NMDA 2A (GluN2A) (Glutamate [NMDA] receptor subunit epsilon-1) (N-methyl D-aspartate receptor subtype 2A) (NMDAR2A) (NR2A) (hNR2A) | Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:20890276, PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:28242877, PubMed:36117210, PubMed:38538865, PubMed:8768735). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:27288002, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28182669, PubMed:29644724, PubMed:38307912, PubMed:8768735). NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761). Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte (By similarity). {ECO:0000250|UniProtKB:P35436, ECO:0000250|UniProtKB:P35438, ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23933818, ECO:0000269|PubMed:23933819, ECO:0000269|PubMed:23933820, ECO:0000269|PubMed:24504326, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27288002, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28182669, ECO:0000269|PubMed:28242877, ECO:0000269|PubMed:29644724, ECO:0000269|PubMed:36117210, ECO:0000269|PubMed:38307912, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:8768735}. |
| Q12888 | TP53BP1 | S1295 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12923 | PTPN13 | S348 | ochoa | Tyrosine-protein phosphatase non-receptor type 13 (EC 3.1.3.48) (Fas-associated protein-tyrosine phosphatase 1) (FAP-1) (PTP-BAS) (Protein-tyrosine phosphatase 1E) (PTP-E1) (hPTPE1) (Protein-tyrosine phosphatase PTPL1) | Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}. |
| Q12929 | EPS8 | S790 | psp | Epidermal growth factor receptor kinase substrate 8 | Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes. {ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031}. |
| Q12959 | DLG1 | S575 | ochoa | Disks large homolog 1 (Synapse-associated protein 97) (SAP-97) (SAP97) (hDlg) | Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). May also play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497). {ECO:0000250|UniProtKB:A0A8C0TYJ0, ECO:0000250|UniProtKB:Q811D0, ECO:0000269|PubMed:10656683, ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15263016, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:23676497}. |
| Q12986 | NFX1 | S346 | ochoa | Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) | Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}. |
| Q13009 | TIAM1 | S329 | psp | Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) | Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}. |
| Q13085 | ACACA | S56 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13127 | REST | S1027 | psp | RE1-silencing transcription factor (Neural-restrictive silencer factor) (X2 box repressor) | Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:11741002, PubMed:11779185, PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247). Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes (PubMed:10449787, PubMed:10734093). Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (PubMed:19061646). Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3 (By similarity). Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes (PubMed:11779185). Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes (By similarity). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:21258371). Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits (By similarity). Acts as a regulator of osteoblast differentiation (By similarity). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions (PubMed:27531581). May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response (PubMed:24670762). Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death (By similarity). After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death (By similarity). Negatively regulates the expression of SRRM3 in breast cancer cell lines (PubMed:26053433). {ECO:0000250|UniProtKB:O54963, ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:10449787, ECO:0000269|PubMed:10734093, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185, ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:26053433, ECO:0000269|PubMed:26551668, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:7697725, ECO:0000269|PubMed:7871435, ECO:0000269|PubMed:8568247}.; FUNCTION: [Isoform 3]: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1 (By similarity). Exhibits weaker repressor activity compared to isoform 1 (PubMed:11779185). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (PubMed:11741002). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing (By similarity). {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185}. |
| Q13191 | CBLB | S662 | ochoa | E3 ubiquitin-protein ligase CBL-B (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene b) (RING finger protein 56) (RING-type E3 ubiquitin transferase CBL-B) (SH3-binding protein CBL-B) (Signal transduction protein CBL-B) | E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:Q3TTA7, ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}. |
| Q13393 | PLD1 | S626 | ochoa | Phospholipase D1 (PLD 1) (hPLD1) (EC 3.1.4.4) (Choline phosphatase 1) (Phosphatidylcholine-hydrolyzing phospholipase D1) | Function as phospholipase selective for phosphatidylcholine (PubMed:25936805, PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). {ECO:0000250|UniProtKB:Q9Z280, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:8530346, ECO:0000269|PubMed:9582313}. |
| Q13422 | IKZF1 | S258 | ochoa | DNA-binding protein Ikaros (Ikaros family zinc finger protein 1) (Lymphoid transcription factor LyF-1) | Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067). {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, ECO:0000269|PubMed:19141594}. |
| Q13586 | STIM1 | S567 | ochoa | Stromal interaction molecule 1 | Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19182790, PubMed:19249086, PubMed:19622606, PubMed:19706554, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:25326555, PubMed:26322679, PubMed:28219928, PubMed:32415068). Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates CRAC channel pore-forming subunits ORA1, ORA2 and ORAI3 to generate sustained and oscillatory Ca(2+) entry (PubMed:16208375, PubMed:16537481, PubMed:32415068). Involved in enamel formation (PubMed:24621671). {ECO:0000269|PubMed:15866891, ECO:0000269|PubMed:16005298, ECO:0000269|PubMed:16208375, ECO:0000269|PubMed:16537481, ECO:0000269|PubMed:16733527, ECO:0000269|PubMed:16766533, ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:18854159, ECO:0000269|PubMed:19182790, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:19622606, ECO:0000269|PubMed:19706554, ECO:0000269|PubMed:22464749, ECO:0000269|PubMed:24069340, ECO:0000269|PubMed:24351972, ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:24621671, ECO:0000269|PubMed:25326555, ECO:0000269|PubMed:26322679, ECO:0000269|PubMed:28219928, ECO:0000269|PubMed:32415068}. |
| Q13596 | SNX1 | S72 | ochoa | Sorting nexin-1 | Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:12198132). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:19816406, PubMed:23085988). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin stxB. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi (PubMed:12198132, PubMed:15498486, PubMed:17101778, PubMed:17550970, PubMed:18088323, PubMed:21040701). Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R (PubMed:16407403, PubMed:20070609). Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901). Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking (PubMed:23152498). {ECO:0000269|PubMed:12198132, ECO:0000269|PubMed:15498486, ECO:0000269|PubMed:16407403, ECO:0000269|PubMed:17101778, ECO:0000269|PubMed:17550970, ECO:0000269|PubMed:18088323, ECO:0000269|PubMed:19816406, ECO:0000269|PubMed:20070609, ECO:0000269|PubMed:20604901, ECO:0000269|PubMed:21040701, ECO:0000269|PubMed:23085988, ECO:0000269|PubMed:23152498, ECO:0000303|PubMed:15498486}. |
| Q13621 | SLC12A1 | S120 | psp | Solute carrier family 12 member 1 (Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1) (BSC1) (Kidney-specific Na-K-Cl symporter) (Na-K-2Cl cotransporter 2) (NKCC2) | Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation (PubMed:21321328). Electrically silent transporter system (By similarity). {ECO:0000250|UniProtKB:P55014, ECO:0000250|UniProtKB:P55016, ECO:0000269|PubMed:21321328}. |
| Q13885 | TUBB2A | S278 | ochoa | Tubulin beta-2A chain (Tubulin beta class IIa) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q14008 | CKAP5 | S845 | ochoa | Cytoskeleton-associated protein 5 (Colonic and hepatic tumor overexpressed gene protein) (Ch-TOG) | Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as a processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448). {ECO:0000269|PubMed:12569123, ECO:0000269|PubMed:18809577, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23532825, ECO:0000269|PubMed:27156448, ECO:0000269|PubMed:9570755}. |
| Q14134 | TRIM29 | S58 | ochoa | Tripartite motif-containing protein 29 (Ataxia telangiectasia group D-associated protein) | Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. Mechanistically, TRIM29 interacts with IKBKG/NEMO in the lysosome where it induces its 'Lys-48' ubiquitination and subsequent degradation. In turn, the expression of type I interferons and the production of pro-inflammatory cytokines are inhibited. Additionally, induces the 'Lys-48' ubiquitination of STING1 in a similar way, leading to its degradation. {ECO:0000269|PubMed:27695001, ECO:0000269|PubMed:29038422}. |
| Q14151 | SAFB2 | S787 | ochoa | Scaffold attachment factor B2 (SAF-B2) | Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation. |
| Q14157 | UBAP2L | S356 | ochoa | Ubiquitin-associated protein 2-like (Protein NICE-4) (RNA polymerase II degradation factor UBAP2L) | Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). Plays an important role in the activity of long-term repopulating hematopoietic stem cells (LT-HSCs) (By similarity). Is a regulator of stress granule assembly, required for their efficient formation (PubMed:29395067, PubMed:35977029). Required for proper brain development and neocortex lamination (By similarity). {ECO:0000250|UniProtKB:Q80X50, ECO:0000269|PubMed:29395067, ECO:0000269|PubMed:35633597}. |
| Q14160 | SCRIB | S1279 | ochoa | Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) | Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750, ECO:0000269|PubMed:27380321}. |
| Q14162 | SCARF1 | S680 | ochoa | Scavenger receptor class F member 1 (Acetyl LDL receptor) (Scavenger receptor expressed by endothelial cells 1) (SREC-I) | Mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). Mediates heterophilic interactions, suggesting a function as adhesion protein. Plays a role in the regulation of neurite-like outgrowth (By similarity). {ECO:0000250}. |
| Q14240 | EIF4A2 | S323 | ochoa | Eukaryotic initiation factor 4A-II (eIF-4A-II) (eIF4A-II) (EC 3.6.4.13) (ATP-dependent RNA helicase eIF4A-2) | ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. |
| Q14244 | MAP7 | S282 | ochoa | Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) | Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}. |
| Q14315 | FLNC | S625 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14315 | FLNC | S762 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14315 | FLNC | S2152 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14524 | SCN5A | S528 | psp | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q14566 | MCM6 | S219 | ochoa | DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| Q14568 | HSP90AA2P | S169 | ochoa | Heat shock protein HSP 90-alpha A2 (Heat shock 90 kDa protein 1 alpha-like 3) (Heat shock protein HSP 90-alpha A2 pseudogene) (Heat shock protein family C member 2) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q14573 | ITPR3 | S1838 | ochoa | Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 (IP3 receptor isoform 3) (IP3R-3) (InsP3R3) (Type 3 inositol 1,4,5-trisphosphate receptor) (Type 3 InsP3 receptor) | Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis (PubMed:32949214, PubMed:37898605, PubMed:8081734, PubMed:8288584). 1D-myo-inositol 1,4,5-trisphosphate binds to the ligand-free channel without altering its global conformation, yielding the low-energy resting state, then progresses through resting-to preactivated transitions to the higher energy preactivated state, which increases affinity for calcium, promoting binding of the low basal cytosolic calcium at the juxtamembrane domain (JD) site, favoring the transition through the ensemble of high-energy intermediate states along the trajectory to the fully-open activated state (PubMed:30013099, PubMed:35301323, PubMed:37898605). Upon opening, releases calcium in the cytosol where it can bind to the low-affinity cytoplasmic domain (CD) site and stabilizes the inhibited state to terminate calcium release (PubMed:30013099, PubMed:35301323, PubMed:37898605). {ECO:0000269|PubMed:30013099, ECO:0000269|PubMed:32949214, ECO:0000269|PubMed:35301323, ECO:0000269|PubMed:37898605, ECO:0000269|PubMed:8081734, ECO:0000269|PubMed:8288584}. |
| Q14624 | ITIH4 | S622 | ochoa | Inter-alpha-trypsin inhibitor heavy chain H4 (ITI heavy chain H4) (ITI-HC4) (Inter-alpha-inhibitor heavy chain 4) (Inter-alpha-trypsin inhibitor family heavy chain-related protein) (IHRP) (Plasma kallikrein sensitive glycoprotein 120) (Gp120) (PK-120) [Cleaved into: 70 kDa inter-alpha-trypsin inhibitor heavy chain H4; 35 kDa inter-alpha-trypsin inhibitor heavy chain H4] | Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration. {ECO:0000269|PubMed:19263524}. |
| Q14669 | TRIP12 | S1113 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14669 | TRIP12 | S1248 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14680 | MELK | S529 | ochoa|psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q14684 | RRP1B | S579 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14966 | ZNF638 | S369 | ochoa | Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) | Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}. |
| Q14D04 | VEPH1 | S425 | ochoa | Ventricular zone-expressed PH domain-containing protein homolog 1 (Protein melted) | Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}. |
| Q15014 | MORF4L2 | S71 | ochoa | Mortality factor 4-like protein 2 (MORF-related gene X protein) (Protein MSL3-2) (Transcription factor-like protein MRGX) | Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also a component of the MSIN3A complex which acts to repress transcription by deacetylation of nucleosomal histones. |
| Q15024 | EXOSC7 | S177 | ochoa | Exosome complex component RRP42 (Exosome component 7) (Ribosomal RNA-processing protein 42) (p8) | Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. |
| Q15043 | SLC39A14 | S309 | ochoa | Metal cation symporter ZIP14 (LIV-1 subfamily of ZIP zinc transporter 4) (LZT-Hs4) (Solute carrier family 39 member 14) (Zrt- and Irt-like protein 14) (ZIP-14) | Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15642354, PubMed:27231142, PubMed:29621230). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (By similarity). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (By similarity). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (By similarity). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (By similarity). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (PubMed:31699897). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (By similarity). Also functions in the extracellular uptake of free iron. May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages (PubMed:23052185). {ECO:0000250|UniProtKB:Q75N73, ECO:0000269|PubMed:15642354, ECO:0000269|PubMed:20682781, ECO:0000269|PubMed:23052185, ECO:0000269|PubMed:27231142, ECO:0000269|PubMed:27703010, ECO:0000269|PubMed:29621230, ECO:0000269|PubMed:31028174, ECO:0000269|PubMed:31699897}. |
| Q15139 | PRKD1 | S548 | ochoa | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q15185 | PTGES3 | S44 | ochoa | Prostaglandin E synthase 3 (EC 5.3.99.3) (Cytosolic prostaglandin E2 synthase) (cPGES) (Hsp90 co-chaperone) (Progesterone receptor complex p23) (Telomerase-binding protein p23) | Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes (PubMed:11274138, PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway (PubMed:24711448). {ECO:0000269|PubMed:10922363, ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12077419, ECO:0000269|PubMed:24711448}. |
| Q15276 | RABEP1 | S416 | ochoa | Rab GTPase-binding effector protein 1 (Rabaptin-4) (Rabaptin-5) (Rabaptin-5alpha) (Renal carcinoma antigen NY-REN-17) | Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Involved in KCNH1 channels trafficking to and from the cell membrane (PubMed:22841712). Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. Mediates the traffic of PKD1:PKD2 complex from the endoplasmic reticulum through the Golgi to the cilium (By similarity). {ECO:0000250|UniProtKB:O35551, ECO:0000269|PubMed:10698684, ECO:0000269|PubMed:11452015, ECO:0000269|PubMed:12773381, ECO:0000269|PubMed:22841712, ECO:0000269|PubMed:8521472}. |
| Q15365 | PCBP1 | S322 | ochoa | Poly(rC)-binding protein 1 (Alpha-CP1) (Heterogeneous nuclear ribonucleoprotein E1) (hnRNP E1) (Nucleic acid-binding protein SUB2.3) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:15731341, PubMed:7556077, PubMed:7607214, PubMed:8152927). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:P60335, ECO:0000269|PubMed:15731341, ECO:0000269|PubMed:7556077, ECO:0000269|PubMed:7607214, ECO:0000269|PubMed:8152927}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD. {ECO:0000269|PubMed:12414943}. |
| Q15417 | CNN3 | S293 | psp | Calponin-3 (Calponin, acidic isoform) | Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity. |
| Q15464 | SHB | S101 | ochoa | SH2 domain-containing adapter protein B | Adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components. May play a role in angiogenesis by regulating FGFR1, VEGFR2 and PDGFR signaling. May also play a role in T-cell antigen receptor/TCR signaling, interleukin-2 signaling, apoptosis and neuronal cells differentiation by mediating basic-FGF and NGF-induced signaling cascades. May also regulate IRS1 and IRS2 signaling in insulin-producing cells. {ECO:0000269|PubMed:10828022, ECO:0000269|PubMed:10837138, ECO:0000269|PubMed:12084069, ECO:0000269|PubMed:12464388, ECO:0000269|PubMed:12520086, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15919073, ECO:0000269|PubMed:8806685, ECO:0000269|PubMed:9484780, ECO:0000269|PubMed:9751119}. |
| Q15696 | ZRSR2 | S355 | ochoa | U2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 (CCCH type zinc finger, RNA-binding motif and serine/arginine rich protein 2) (Renal carcinoma antigen NY-REN-20) (U2(RNU2) small nuclear RNA auxiliary factor 1-like 2) (U2AF35-related protein) (URP) | Pre-mRNA-binding protein required for splicing of both U2- and U12-type introns. Selectively interacts with the 3'-splice site of U2- and U12-type pre-mRNAs and promotes different steps in U2 and U12 intron splicing. Recruited to U12 pre-mRNAs in an ATP-dependent manner and is required for assembly of the pre-spliceosome, a precursor to other spliceosomal complexes. For U2-type introns, it is selectively and specifically required for the second step of splicing. {ECO:0000269|PubMed:21041408, ECO:0000269|PubMed:9237760}. |
| Q15835 | GRK1 | S21 | psp | Rhodopsin kinase GRK1 (RK) (EC 2.7.11.14) (G protein-coupled receptor kinase 1) | Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade (PubMed:15946941). This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination (By similarity). May play a role in the maintenance of the outer nuclear layer in the retina (By similarity). {ECO:0000250|UniProtKB:Q9WVL4, ECO:0000269|PubMed:15946941}. |
| Q15906 | VPS72 | S127 | ochoa | Vacuolar protein sorting-associated protein 72 homolog (Protein YL-1) (Transcription factor-like 1) | Deposition-and-exchange histone chaperone specific for H2AZ1, specifically chaperones H2AZ1 and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP-dependent exchange of histone H2AZ1/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. {ECO:0000269|PubMed:26974126}. |
| Q15911 | ZFHX3 | S1353 | ochoa | Zinc finger homeobox protein 3 (AT motif-binding factor 1) (AT-binding transcription factor 1) (Alpha-fetoprotein enhancer-binding protein) (Zinc finger homeodomain protein 3) (ZFH-3) | Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signaling can repress the transcription of AFP via its interaction with SMAD2/3 (PubMed:25105025). Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain (By similarity). Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression (PubMed:11312261). Down-regulates the MUC5AC promoter in gastric cancer (PubMed:17330845). In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712). Inhibits estrogen receptor (ESR1) function by selectively competing with coactivator NCOA3 for binding to ESR1 in ESR1-positive breast cancer cells (PubMed:20720010). {ECO:0000250|UniProtKB:Q61329, ECO:0000269|PubMed:11312261, ECO:0000269|PubMed:17330845, ECO:0000269|PubMed:20599712, ECO:0000269|PubMed:20720010, ECO:0000269|PubMed:25105025}. |
| Q16576 | RBBP7 | S109 | ochoa | Histone-binding protein RBBP7 (Histone acetyltransferase type B subunit 2) (Nucleosome-remodeling factor subunit RBAP46) (Retinoblastoma-binding protein 7) (RBBP-7) (Retinoblastoma-binding protein p46) | Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex. {ECO:0000269|PubMed:10866654, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| Q16821 | PPP1R3A | S987 | ochoa | Protein phosphatase 1 regulatory subunit 3A (Protein phosphatase 1 glycogen-associated regulatory subunit) (Protein phosphatase type-1 glycogen targeting subunit) (RG1) | Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase (By similarity). {ECO:0000250}. |
| Q2KJY2 | KIF26B | S1144 | ochoa | Kinesin-like protein KIF26B | Essential for embryonic kidney development. Plays an important role in the compact adhesion between mesenchymal cells adjacent to the ureteric buds, possibly by interacting with MYH10. This could lead to the establishment of the basolateral integrity of the mesenchyme and the polarized expression of ITGA8, which maintains the GDNF expression required for further ureteric bud attraction. Although it seems to lack ATPase activity it is constitutively associated with microtubules (By similarity). {ECO:0000250}. |
| Q2M1Z3 | ARHGAP31 | S387 | ochoa | Rho GTPase-activating protein 31 (Cdc42 GTPase-activating protein) | Functions as a GTPase-activating protein (GAP) for RAC1 and CDC42. Required for cell spreading, polarized lamellipodia formation and cell migration. {ECO:0000269|PubMed:12192056, ECO:0000269|PubMed:16519628}. |
| Q32MZ4 | LRRFIP1 | S78 | ochoa | Leucine-rich repeat flightless-interacting protein 1 (LRR FLII-interacting protein 1) (GC-binding factor 2) (TAR RNA-interacting protein) | Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:10364563, ECO:0000269|PubMed:14522076, ECO:0000269|PubMed:16199883, ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:9705290}. |
| Q3ZCM7 | TUBB8 | S278 | ochoa | Tubulin beta-8 chain (Tubulin beta 8 class VIII) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. TUBB8 has a key role in meiotic spindle assembly and oocyte maturation (PubMed:26789871, PubMed:34509376). {ECO:0000269|PubMed:26789871, ECO:0000269|PubMed:34509376}. |
| Q4VCS5 | AMOT | S823 | ochoa | Angiomotin | Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions. Repressor of YAP1 and WWTR1/TAZ transcription of target genes, potentially via regulation of Hippo signaling-mediated phosphorylation of YAP1 which results in its recruitment to tight junctions (PubMed:21205866). {ECO:0000269|PubMed:11257124, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:21205866}. |
| Q53GG5 | PDLIM3 | S252 | ochoa | PDZ and LIM domain protein 3 (Actinin-associated LIM protein) (Alpha-actinin-2-associated LIM protein) | May play a role in the organization of actin filament arrays within muscle cells. {ECO:0000250}. |
| Q53GG5 | PDLIM3 | S264 | ochoa | PDZ and LIM domain protein 3 (Actinin-associated LIM protein) (Alpha-actinin-2-associated LIM protein) | May play a role in the organization of actin filament arrays within muscle cells. {ECO:0000250}. |
| Q5BKX6 | SLC45A4 | S43 | ochoa | Solute carrier family 45 member 4 | Proton-associated sucrose transporter. May be able to transport also glucose and fructose. {ECO:0000250|UniProtKB:Q0P5V9}. |
| Q5JSZ5 | PRRC2B | S1754 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JTH9 | RRP12 | S66 | ochoa | RRP12-like protein | None |
| Q5JTV8 | TOR1AIP1 | S39 | ochoa | Torsin-1A-interacting protein 1 (Lamin-associated protein 1B) (LAP1B) | Required for nuclear membrane integrity. Induces TOR1A and TOR1B ATPase activity and is required for their location on the nuclear membrane. Binds to A- and B-type lamins. Possible role in membrane attachment and assembly of the nuclear lamina. {ECO:0000269|PubMed:23569223}. |
| Q5M7Z0 | RNFT1 | S53 | ochoa | E3 ubiquitin-protein ligase RNFT1 (EC 2.3.2.27) (Protein PTD016) (RING finger and transmembrane domain-containing protein 1) | E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis. {ECO:0000269|PubMed:27485036}. |
| Q5R3F8 | ELFN2 | S451 | ochoa | Protein phosphatase 1 regulatory subunit 29 (Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2) (Leucine-rich repeat and fibronectin type-III domain-containing protein 6) (Leucine-rich repeat-containing protein 62) | Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000269|PubMed:19389623}. |
| Q5R3F8 | ELFN2 | S530 | ochoa | Protein phosphatase 1 regulatory subunit 29 (Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2) (Leucine-rich repeat and fibronectin type-III domain-containing protein 6) (Leucine-rich repeat-containing protein 62) | Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. {ECO:0000269|PubMed:19389623}. |
| Q5S007 | LRRK2 | S860 | psp | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q5SW79 | CEP170 | S1223 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5SWA1 | PPP1R15B | S614 | ochoa | Protein phosphatase 1 regulatory subunit 15B | Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1. {ECO:0000269|PubMed:26159176, ECO:0000269|PubMed:26307080}. |
| Q5SY16 | NOL9 | S241 | ochoa | Polynucleotide 5'-hydroxyl-kinase NOL9 (EC 2.7.1.78) (Nucleolar protein 9) | Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of single-stranded and double-stranded RNA and DNA substrates (PubMed:21063389). Involved in rRNA processing and its kinase activity is required for the processing of the 32S precursor into 5.8S and 28S rRNAs, more specifically for the generation of the major 5.8S(S) form (PubMed:21063389). Required for the efficient pre-rRNA processing of internal transcribed spacer 2 (ITS2) (PubMed:21063389). Associates with LAS1L to form an ITS2 pre-rRNA endonuclease-kinase complex and is responsible for the transport of this complex into the nucleolus (PubMed:31288032). {ECO:0000269|PubMed:21063389, ECO:0000269|PubMed:31288032}. |
| Q5T0Z8 | C6orf132 | S867 | ochoa | Uncharacterized protein C6orf132 | None |
| Q5T1M5 | FKBP15 | S1024 | ochoa | FK506-binding protein 15 (FKBP-15) (133 kDa FK506-binding protein) (133 kDa FKBP) (FKBP-133) (WASP- and FKBP-like protein) (WAFL) | May be involved in the cytoskeletal organization of neuronal growth cones. Seems to be inactive as a PPIase (By similarity). Involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement. {ECO:0000250, ECO:0000269|PubMed:19121306}. |
| Q5T200 | ZC3H13 | S578 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5T200 | ZC3H13 | S1232 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5TCZ1 | SH3PXD2A | S795 | ochoa | SH3 and PX domain-containing protein 2A (Adapter protein TKS5) (Five SH3 domain-containing protein) (SH3 multiple domains protein 1) (Tyrosine kinase substrate with five SH3 domains) | Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells (PubMed:27789576). Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328, ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497, ECO:0000269|PubMed:27789576}. |
| Q5TH69 | ARFGEF3 | S632 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (ARFGEF family member 3) | Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8, ECO:0000269|PubMed:19496786}. |
| Q5VST9 | OBSCN | S2326 | ochoa | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q5VV41 | ARHGEF16 | S208 | ochoa | Rho guanine nucleotide exchange factor 16 (Ephexin-4) | Guanyl-nucleotide exchange factor of the RHOG GTPase stimulating the exchange of RHOG-associated GDP for GTP. May play a role in chemotactic cell migration by mediating the activation of RAC1 by EPHA2. May also activate CDC42 and mediate activation of CDC42 by the viral protein HPV16 E6. {ECO:0000269|PubMed:20679435}. |
| Q5VYK3 | ECPAS | S833 | ochoa | Proteasome adapter and scaffold protein ECM29 (Ecm29 proteasome adapter and scaffold) (Proteasome-associated protein ECM29 homolog) | Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins. May couple the proteasome to different compartments including endosome, endoplasmic reticulum and centrosome. May play a role in ERAD and other enhanced proteolysis (PubMed:15496406). Promotes proteasome dissociation under oxidative stress (By similarity). {ECO:0000250|UniProtKB:Q6PDI5, ECO:0000269|PubMed:15496406, ECO:0000269|PubMed:20682791}. |
| Q63HN8 | RNF213 | S3525 | ochoa | E3 ubiquitin-protein ligase RNF213 (EC 2.3.2.27) (EC 3.6.4.-) (ALK lymphoma oligomerization partner on chromosome 17) (E3 ubiquitin-lipopolysaccharide ligase RNF213) (EC 2.3.2.-) (Mysterin) (RING finger protein 213) | Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115). {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, ECO:0000269|PubMed:26766444, ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:30846318, ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849, ECO:0000269|PubMed:34012115}. |
| Q658Y4 | FAM91A1 | S691 | ochoa | Protein FAM91A1 | As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1. {ECO:0000269|PubMed:29426865}. |
| Q68DC2 | ANKS6 | S660 | ochoa | Ankyrin repeat and SAM domain-containing protein 6 (Ankyrin repeat domain-containing protein 14) (SamCystin) (Sterile alpha motif domain-containing protein 6) (SAM domain-containing protein 6) | Required for renal function. {ECO:0000269|PubMed:23793029}. |
| Q68DQ2 | CRYBG3 | S177 | ochoa | Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) | [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}. |
| Q6GQQ9 | OTUD7B | S508 | ochoa | OTU domain-containing protein 7B (EC 3.4.19.12) (Cellular zinc finger anti-NF-kappa-B protein) (Cezanne) (Zinc finger A20 domain-containing protein 1) (Zinc finger protein Cezanne) | Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses (PubMed:18178551). In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (By similarity). Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:11463333, PubMed:20622874, PubMed:23827681, PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin (PubMed:12682062). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked deubiquitination of MLST8, thereby promoting assembly of the mTORC2 complex, while inibiting formation of the mTORC1 complex (PubMed:28489822). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584, ECO:0000269|PubMed:28489822}. |
| Q6GTX8 | LAIR1 | S245 | ochoa | Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) (hLAIR1) (CD antigen CD305) | Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Also down-regulates IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells. {ECO:0000269|PubMed:10229813, ECO:0000269|PubMed:10764762, ECO:0000269|PubMed:11069054, ECO:0000269|PubMed:11160222, ECO:0000269|PubMed:12072189, ECO:0000269|PubMed:15939744, ECO:0000269|PubMed:15950745, ECO:0000269|PubMed:16380958, ECO:0000269|PubMed:9285412, ECO:0000269|PubMed:9692876}. |
| Q6NSZ9 | ZSCAN25 | S272 | ochoa | Zinc finger and SCAN domain-containing protein 25 (Zinc finger protein 498) | May be involved in transcriptional regulation. {ECO:0000250}. |
| Q6NUJ5 | PWWP2B | S276 | ochoa | PWWP domain-containing protein 2B | Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes (PubMed:30228260). Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z (PubMed:30228260). Plays a role in facilitating transcriptional elongation through regulation of histone acetylation (By similarity). Negatively regulates brown adipocyte thermogenesis by interacting with and stabilizing HDAC1 at the UCP1 gene promoter, thereby promoting histone deacetylation at the promoter leading to the repression of UCP1 expression (By similarity). {ECO:0000250|UniProtKB:Q69Z61, ECO:0000269|PubMed:30228260}. |
| Q6NXE6 | ARMC6 | S84 | ochoa | Armadillo repeat-containing protein 6 | None |
| Q6NZI2 | CAVIN1 | S40 | ochoa | Caveolae-associated protein 1 (Cavin-1) (Polymerase I and transcript release factor) | Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues (PubMed:18056712, PubMed:18191225, PubMed:19726876). Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1). Essential for normal oligomerization of CAV1. Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop. Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template (By similarity) (PubMed:18056712, PubMed:18191225, PubMed:19726876). The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A (By similarity). {ECO:0000250|UniProtKB:O54724, ECO:0000269|PubMed:18056712, ECO:0000269|PubMed:18191225, ECO:0000269|PubMed:19726876}. |
| Q6P1M3 | LLGL2 | S680 | ochoa | LLGL scribble cell polarity complex component 2 (HGL) (Lethal(2) giant larvae protein homolog 2) | Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity. {ECO:0000269|PubMed:15632202}. |
| Q6P4E1 | GOLM2 | S374 | ochoa | Protein GOLM2 (Cancer susceptibility candidate gene 4 protein) (CASC4) (Golgi membrane protein 2) | None |
| Q6P4R8 | NFRKB | S799 | ochoa | Nuclear factor related to kappa-B-binding protein (DNA-binding protein R kappa-B) (INO80 complex subunit G) | Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'. {ECO:0000269|PubMed:18922472}.; FUNCTION: Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex. {ECO:0000269|PubMed:18922472}. |
| Q6P996 | PDXDC1 | S669 | ochoa | Pyridoxal-dependent decarboxylase domain-containing protein 1 (EC 4.1.1.-) | None |
| Q6PJ69 | TRIM65 | S367 | psp | E3 ubiquitin-protein ligase TRIM65 (EC 2.3.2.27) (Tripartite motif-containing protein 65) | E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:28594402, PubMed:34512673). Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252). This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576). Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402). Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584). Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649). In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673). {ECO:0000269|PubMed:24778252, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:31160576, ECO:0000269|PubMed:31310649, ECO:0000269|PubMed:33373584, ECO:0000269|PubMed:34512673}. |
| Q6PL24 | TMED8 | S21 | ochoa | Protein TMED8 | None |
| Q6R327 | RICTOR | S1585 | ochoa | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6STE5 | SMARCD3 | S178 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 (60 kDa BRG-1/Brm-associated factor subunit C) (BRG1-associated factor 60C) (BAF60C) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Stimulates nuclear receptor mediated transcription. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6P9Z1, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:8804307, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q6UB99 | ANKRD11 | S2374 | ochoa | Ankyrin repeat domain-containing protein 11 (Ankyrin repeat-containing cofactor 1) | Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (By similarity). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (PubMed:15184363). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). May also regulate bone homeostasis (By similarity). {ECO:0000250|UniProtKB:E9Q4F7, ECO:0000269|PubMed:15184363, ECO:0000269|PubMed:25556659}. |
| Q6UN15 | FIP1L1 | S112 | ochoa | Pre-mRNA 3'-end-processing factor FIP1 (hFip1) (FIP1-like 1 protein) (Factor interacting with PAP) (Rearranged in hypereosinophilia) | Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex. {ECO:0000269|PubMed:14749727}. |
| Q6UUV9 | CRTC1 | S73 | ochoa | CREB-regulated transcription coactivator 1 (Mucoepidermoid carcinoma translocated protein 1) (Transducer of regulated cAMP response element-binding protein 1) (TORC-1) (Transducer of CREB protein 1) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons (By similarity). In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock. {ECO:0000250|UniProtKB:Q157S1, ECO:0000250|UniProtKB:Q68ED7, ECO:0000269|PubMed:23699513}.; FUNCTION: (Microbial infection) Plays a role of coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:16809310}. |
| Q6UXY1 | BAIAP2L2 | S427 | ochoa | BAR/IMD domain-containing adapter protein 2-like 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2) (BAI1-associated protein 2-like protein 2) (Planar intestinal- and kidney-specific BAR domain protein) (Pinkbar) | Phosphoinositides-binding protein that induces the formation of planar or gently curved membrane structures. Binds to phosphoinositides, including to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) headgroups. There seems to be no clear preference for a specific phosphoinositide (By similarity). {ECO:0000250}. |
| Q6ZNB6 | NFXL1 | S331 | ochoa | NF-X1-type zinc finger protein NFXL1 (Ovarian zinc finger protein) (hOZFP) | None |
| Q70CQ2 | USP34 | S718 | psp | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| Q70CQ2 | USP34 | S2401 | ochoa | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| Q71H61 | ILDR2 | S547 | ochoa | Immunoglobulin-like domain-containing receptor 2 (Angulin-3) | May be involved in ER stress pathways with effects on lipid homeostasis and insulin secretion. With ILDR1 and LSR, involved in the maintain of the epithelial barrier function through the recruitment of MARVELD2/tricellulin to tricellular tight junctions (By similarity). Also functions as a B7-like protein family member expressed on immune cells and inflamed tissue and with T-cell inhibitory activity (PubMed:29431694). In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1 (By similarity). {ECO:0000250|UniProtKB:B5TVM2, ECO:0000269|PubMed:29431694}. |
| Q71RC2 | LARP4 | S385 | ochoa | La-related protein 4 (La ribonucleoprotein domain family member 4) | RNA binding protein that binds to the poly-A tract of mRNA molecules (PubMed:21098120). Associates with the 40S ribosomal subunit and with polysomes (PubMed:21098120). Plays a role in the regulation of mRNA translation (PubMed:21098120). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987, PubMed:27615744). {ECO:0000269|PubMed:21098120, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:27615744}. |
| Q765P7 | MTSS2 | S612 | ochoa | Protein MTSS 2 (Actin-bundling with BAIAP2 homology protein 1) (ABBA-1) (MTSS1-like protein) | Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}. |
| Q7KZF4 | SND1 | S238 | ochoa | Staphylococcal nuclease domain-containing protein 1 (EC 3.1.31.1) (100 kDa coactivator) (EBNA2 coactivator p100) (Tudor domain-containing protein 11) (p100 co-activator) | Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (PubMed:18453631, PubMed:28546213). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition (PubMed:28546213). Functions as a bridging factor between STAT6 and the basal transcription factor (PubMed:12234934). Plays a role in PIM1 regulation of MYB activity (PubMed:9809063). Functions as a transcriptional coactivator for STAT5 (By similarity). {ECO:0000250|UniProtKB:Q78PY7, ECO:0000269|PubMed:12234934, ECO:0000269|PubMed:18453631, ECO:0000269|PubMed:28546213, ECO:0000269|PubMed:9809063}.; FUNCTION: (Microbial infection) Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2). {ECO:0000269|PubMed:7651391}.; FUNCTION: (Microbial infection) Promotes SARS-CoV-2 RNA synthesis by binding to negative-sense RNA and the viral protein nsp9. {ECO:0000269|PubMed:37794589}. |
| Q7L273 | KCTD9 | S318 | ochoa | BTB/POZ domain-containing protein KCTD9 | Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome. {ECO:0000305}. |
| Q7L4E1 | MIGA2 | S276 | ochoa | Mitoguardin 2 (Protein FAM73B) | Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD. {ECO:0000269|PubMed:26711011}. |
| Q7Z2K8 | GPRIN1 | S341 | ochoa | G protein-regulated inducer of neurite outgrowth 1 (GRIN1) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q7Z3C6 | ATG9A | S675 | ochoa | Autophagy-related protein 9A (APG9-like 1) (mATG9) | Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:22456507, PubMed:27510922, PubMed:29437695, PubMed:32513819, PubMed:32610138, PubMed:33106659, PubMed:33468622, PubMed:33850023). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome (PubMed:16940348, PubMed:22456507, PubMed:33106659). Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion (PubMed:33106659). Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1 (PubMed:30917996). In addition to autophagy, also plays a role in necrotic cell death (By similarity). {ECO:0000250|UniProtKB:Q68FE2, ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:27510922, ECO:0000269|PubMed:29437695, ECO:0000269|PubMed:30917996, ECO:0000269|PubMed:32513819, ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659, ECO:0000269|PubMed:33468622, ECO:0000269|PubMed:33850023}. |
| Q7Z3J3 | RGPD4 | S1543 | ochoa | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q7Z3K3 | POGZ | S348 | ochoa | Pogo transposable element with ZNF domain (Suppressor of hairy wing homolog 5) (Zinc finger protein 280E) (Zinc finger protein 635) | Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms (PubMed:20562864). Promotes the repair of DNA double-strand breaks through the homologous recombination pathway (PubMed:26721387). {ECO:0000269|PubMed:20562864, ECO:0000269|PubMed:26721387}. |
| Q7Z401 | DENND4A | S1609 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z412 | PEX26 | S224 | ochoa | Peroxisome assembly protein 26 (Peroxin-26) | Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes (PubMed:12717447, PubMed:12851857, PubMed:16257970, PubMed:16763195, PubMed:16854980, PubMed:21362118). PEX26 is therefore required for the formation of the PEX1-PEX6 AAA ATPase complex, a complex that mediates the extraction of the PEX5 receptor from peroxisomal membrane (PubMed:12717447, PubMed:12851857, PubMed:16257970, PubMed:16763195, PubMed:16854980, PubMed:21362118). {ECO:0000269|PubMed:12717447, ECO:0000269|PubMed:12851857, ECO:0000269|PubMed:16257970, ECO:0000269|PubMed:16763195, ECO:0000269|PubMed:16854980, ECO:0000269|PubMed:21362118}. |
| Q7Z417 | NUFIP2 | S214 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z460 | CLASP1 | S594 | ochoa | CLIP-associating protein 1 (Cytoplasmic linker-associated protein 1) (Multiple asters homolog 1) (Protein Orbit homolog 1) (hOrbit1) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}. |
| Q7Z6B7 | SRGAP1 | S917 | ochoa | SLIT-ROBO Rho GTPase-activating protein 1 (srGAP1) (Rho GTPase-activating protein 13) | GTPase-activating protein for RhoA and Cdc42 small GTPases. Together with CDC42 seems to be involved in the pathway mediating the repulsive signaling of Robo and Slit proteins in neuronal migration. SLIT2, probably through interaction with ROBO1, increases the interaction of SRGAP1 with ROBO1 and inactivates CDC42. {ECO:0000269|PubMed:11672528}. |
| Q7Z6Z7 | HUWE1 | S1298 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z7G8 | VPS13B | S1002 | ochoa | Intermembrane lipid transfer protein VPS13B (Cohen syndrome protein 1) (Vacuolar protein sorting-associated protein 13B) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phosphatidylinositol 3-phosphate (By similarity). Functions as a tethering factor in the slow endocytic recycling pathway, to assist traffic between early and recycling endosomes (PubMed:24334764, PubMed:30962439, PubMed:32375900). Involved in the transport of proacrosomal vesicles to the nuclear dense lamina (NDL) during spermatid development (By similarity). Plays a role in the assembly of the Golgi apparatus, possibly by mediating trafficking to the Golgi membrane (PubMed:21865173). Plays a role in the development of the nervous system, and may be required for neuron projection development (PubMed:25492866, PubMed:32560273). May also play a role during adipose tissue development (PubMed:26358774). Required for maintenance of the ocular lens (By similarity). {ECO:0000250|UniProtKB:Q07878, ECO:0000250|UniProtKB:Q80TY5, ECO:0000269|PubMed:21865173, ECO:0000269|PubMed:24334764, ECO:0000269|PubMed:26358774, ECO:0000269|PubMed:30962439, ECO:0000269|PubMed:32375900, ECO:0000269|PubMed:32560273, ECO:0000305|PubMed:25492866, ECO:0000305|PubMed:32560273}. |
| Q86SQ0 | PHLDB2 | S937 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86TC9 | MYPN | S609 | ochoa | Myopalladin (145 kDa sarcomeric protein) | Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines. {ECO:0000269|PubMed:11309420}. |
| Q86U42 | PABPN1 | S197 | ochoa | Polyadenylate-binding protein 2 (PABP-2) (Poly(A)-binding protein 2) (Nuclear poly(A)-binding protein 1) (Poly(A)-binding protein II) (PABII) (Polyadenylate-binding nuclear protein 1) | Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product (By similarity). Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and also controls the poly(A) tail length (By similarity). Increases the affinity of poly(A) polymerase for RNA (By similarity). Is also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking and nonsense-mediated decay (NMD) of mRNA. Cooperates with SKIP to synergistically activate E-box-mediated transcription through MYOD1 and may regulate the expression of muscle-specific genes (PubMed:11371506). Binds to poly(A) and to poly(G) with high affinity (By similarity). May protect the poly(A) tail from degradation (By similarity). Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484). {ECO:0000250|UniProtKB:Q28165, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:27871484}. |
| Q86U86 | PBRM1 | S319 | ochoa | Protein polybromo-1 (hPB1) (BRG1-associated factor 180) (BAF180) (Polybromo-1D) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation. {ECO:0000269|PubMed:21248752, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q86UE8 | TLK2 | S134 | ochoa | Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) | Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}. |
| Q86UR5 | RIMS1 | S1414 | ochoa | Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) | Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}. |
| Q86UR5 | RIMS1 | S1493 | ochoa | Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) | Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}. |
| Q86YS7 | C2CD5 | S606 | ochoa | C2 domain-containing protein 5 (C2 domain-containing phosphoprotein of 138 kDa) | Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM. {ECO:0000269|PubMed:21907143}. |
| Q8IVH8 | MAP4K3 | S507 | ochoa | Mitogen-activated protein kinase kinase kinase kinase 3 (EC 2.7.11.1) (Germinal center kinase-related protein kinase) (GLK) (MAPK/ERK kinase kinase kinase 3) (MEK kinase kinase 3) (MEKKK 3) | Serine/threonine kinase that plays a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway (PubMed:9275185). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:9275185}. |
| Q8IVL1 | NAV2 | S1019 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IW93 | ARHGEF19 | S350 | ochoa | Rho guanine nucleotide exchange factor 19 (Ephexin-2) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPase. {ECO:0000250}. |
| Q8IWU5 | SULF2 | S838 | ochoa | Extracellular sulfatase Sulf-2 (hSulf-2) (Arylsulfatase) (EC 3.1.6.1) (N-acetylglucosamine-6-sulfatase) (EC 3.1.6.14) [Cleaved into: Extracellular sulfatase Sulf-2 secreted form] | Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity (PubMed:12368295, PubMed:30788513, PubMed:35294879). It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin (PubMed:12368295, PubMed:30788513, PubMed:35294879). {ECO:0000269|PubMed:12368295, ECO:0000269|PubMed:30788513, ECO:0000269|PubMed:35294879}. |
| Q8IWZ8 | SUGP1 | S326 | ochoa | SURP and G-patch domain-containing protein 1 (RNA-binding protein RBP) (Splicing factor 4) | Plays a role in pre-mRNA splicing. |
| Q8IX01 | SUGP2 | S224 | ochoa | SURP and G-patch domain-containing protein 2 (Arginine/serine-rich-splicing factor 14) (Splicing factor, arginine/serine-rich 14) | May play a role in mRNA splicing. {ECO:0000305}. |
| Q8IX01 | SUGP2 | S1032 | ochoa | SURP and G-patch domain-containing protein 2 (Arginine/serine-rich-splicing factor 14) (Splicing factor, arginine/serine-rich 14) | May play a role in mRNA splicing. {ECO:0000305}. |
| Q8N163 | CCAR2 | S814 | ochoa | Cell cycle and apoptosis regulator protein 2 (Cell division cycle and apoptosis regulator protein 2) (DBIRD complex subunit KIAA1967) (Deleted in breast cancer gene 1 protein) (DBC-1) (DBC.1) (NET35) (p30 DBC) | Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions (PubMed:22446626). Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis (PubMed:18235501, PubMed:18235502, PubMed:23352644). Inhibits SUV39H1 methyltransferase activity (PubMed:19218236). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:19131338). Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress (PubMed:23398316). Regulates the circadian expression of the core clock components NR1D1 and BMAL1 (PubMed:23398316). Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978). {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}. |
| Q8N1F7 | NUP93 | S66 | ochoa | Nuclear pore complex protein Nup93 (93 kDa nucleoporin) (Nucleoporin Nup93) | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling (PubMed:26878725). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:15703211, ECO:0000269|PubMed:26878725, ECO:0000269|PubMed:9348540}. |
| Q8N1G4 | LRRC47 | S561 | ochoa | Leucine-rich repeat-containing protein 47 | None |
| Q8N1K5 | THEMIS | S611 | ochoa | Protein THEMIS (Thymocyte-expressed molecule involved in selection) | Plays a central role in late thymocyte development by controlling both positive and negative T-cell selection. Required to sustain and/or integrate signals required for proper lineage commitment and maturation of T-cells. Regulates T-cell development through T-cell antigen receptor (TCR) signaling and in particular through the regulation of calcium influx and phosphorylation of Erk. {ECO:0000250|UniProtKB:Q8BGW0}. |
| Q8N3D4 | EHBP1L1 | S1273 | ochoa | EH domain-binding protein 1-like protein 1 | May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000305|PubMed:27552051}. |
| Q8N3U4 | STAG2 | S1068 | ochoa | Cohesin subunit SA-2 (SCC3 homolog 2) (Stromal antigen 2) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}. |
| Q8N3X1 | FNBP4 | S671 | ochoa | Formin-binding protein 4 (Formin-binding protein 30) | None |
| Q8N4S9 | MARVELD2 | S140 | ochoa | MARVEL domain-containing protein 2 (Tricellulin) | Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:17186462). {ECO:0000250|UniProtKB:Q3UZP0, ECO:0000269|PubMed:17186462}. |
| Q8N4X5 | AFAP1L2 | S309 | ochoa | Actin filament-associated protein 1-like 2 (AFAP1-like protein 2) | May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269|PubMed:17412687}. |
| Q8N573 | OXR1 | S307 | ochoa | Oxidation resistance protein 1 | May be involved in protection from oxidative damage. {ECO:0000269|PubMed:11114193, ECO:0000269|PubMed:15060142}. |
| Q8N5I9 | NOPCHAP1 | S34 | ochoa | NOP protein chaperone 1 | Client-loading PAQosome/R2TP complex cofactor that selects NOP58 to promote box C/D small nucleolar ribonucleoprotein (snoRNP) assembly. Acts as a bridge between NOP58 and the R2TP complex via RUVBL1:RUVBL2. {ECO:0000269|PubMed:33367824}. |
| Q8N8Z6 | DCBLD1 | S556 | ochoa|psp | Discoidin, CUB and LCCL domain-containing protein 1 | None |
| Q8N9M1 | C19orf47 | S395 | ochoa | Uncharacterized protein C19orf47 | None |
| Q8NBR6 | MINDY2 | S25 | ochoa | Ubiquitin carboxyl-terminal hydrolase MINDY-2 (EC 3.4.19.12) (Deubiquitinating enzyme MINDY-2) (Protein FAM63B) | Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798). {ECO:0000269|PubMed:27292798, ECO:0000269|PubMed:28082312}. |
| Q8NCN2 | ZBTB34 | S207 | ochoa | Zinc finger and BTB domain-containing protein 34 | May be a transcriptional repressor. {ECO:0000269|PubMed:16718364}. |
| Q8NCN4 | RNF169 | S636 | ochoa | E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) | Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}. |
| Q8NE01 | CNNM3 | S673 | ochoa | Metal transporter CNNM3 (Ancient conserved domain-containing protein 3) (Cyclin-M3) | Probable metal transporter. {ECO:0000250}. |
| Q8NEV8 | EXPH5 | S318 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NF99 | ZNF397 | S242 | ochoa | Zinc finger protein 397 (Zinc finger and SCAN domain-containing protein 15) (Zinc finger protein 47) | Isoform 3 acts as a DNA-dependent transcriptional repressor. {ECO:0000269|PubMed:12801647}. |
| Q8NFA0 | USP32 | S1416 | ochoa | Ubiquitin carboxyl-terminal hydrolase 32 (EC 3.4.19.12) (Deubiquitinating enzyme 32) (Renal carcinoma antigen NY-REN-60) (Ubiquitin thioesterase 32) (Ubiquitin-specific-processing protease 32) | Deubiquitinase that can remove conjugated ubiquitin from target proteins, such as RAB7A and LAMTOR1 (PubMed:36476874). Acts as a positive regulator of the mTORC1 signaling by mediating deubiquitination of LAMTOR1, thereby promoting the association between LAMTOR1 and the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (PubMed:36476874). {ECO:0000269|PubMed:36476874}. |
| Q8NFC6 | BOD1L1 | S1701 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFM4 | ADCY4 | S253 | ochoa | Adenylate cyclase type 4 (EC 4.6.1.1) (ATP pyrophosphate-lyase 4) (Adenylate cyclase type IV) (Adenylyl cyclase 4) | Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. {ECO:0000250|UniProtKB:P26770}. |
| Q8NHM5 | KDM2B | S746 | ochoa | Lysine-specific demethylase 2B (EC 1.14.11.27) (CXXC-type zinc finger protein 2) (F-box and leucine-rich repeat protein 10) (F-box protein FBL10) (F-box/LRR-repeat protein 10) (JmjC domain-containing histone demethylation protein 1B) (Jumonji domain-containing EMSY-interactor methyltransferase motif protein) (Protein JEMMA) (Protein-containing CXXC domain 2) ([Histone-H3]-lysine-36 demethylase 1B) | Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}. |
| Q8NHQ8 | RASSF8 | S387 | ochoa | Ras association domain-containing protein 8 (Carcinoma-associated protein HOJ-1) | None |
| Q8NHS3 | MFSD8 | S20 | ochoa | Major facilitator superfamily domain-containing protein 8 (Ceroid-lipofuscinosis neuronal protein 7) | Outward-rectifying chloride channel involved in endolysosomal chloride homeostasis, membrane fusion and function. Conducts chloride currents up to hundreds of picoamperes. Regulates lysosomal calcium content by reducing the lysosomal membrane potential, thereby activating TRPML1 channel and further release of lysosomal calcium ions. Regulates the pH in endolysosomal compartments and may contribute to progressive acidification from endosome to lysosome. Permeable to other halides such as iodide and fluoride ions. {ECO:0000269|PubMed:34910516}. |
| Q8NHV4 | NEDD1 | S423 | ochoa|psp | Protein NEDD1 (Neural precursor cell expressed developmentally down-regulated protein 1) (NEDD-1) | Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19509060}. |
| Q8NHY2 | COP1 | S110 | ochoa | E3 ubiquitin-protein ligase COP1 (EC 2.3.2.27) (Constitutive photomorphogenesis protein 1 homolog) (hCOP1) (RING finger and WD repeat domain protein 2) (RING finger protein 200) (RING-type E3 ubiquitin transferase RFWD2) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif (Probable). {ECO:0000269|PubMed:12466024, ECO:0000269|PubMed:12615916, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15103385, ECO:0000269|PubMed:19805145, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21625211, ECO:0000303|PubMed:27041596}. |
| Q8TCU6 | PREX1 | S1195 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein (P-Rex1) (PtdIns(3,4,5)-dependent Rac exchanger 1) | Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils. |
| Q8TDB6 | DTX3L | S614 | ochoa | E3 ubiquitin-protein ligase DTX3L (EC 2.3.2.27) (B-lymphoma- and BAL-associated protein) (Protein deltex-3-like) (RING-type E3 ubiquitin transferase DTX3L) (Rhysin-2) (Rhysin2) | E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses (PubMed:12670957, PubMed:19818714, PubMed:23230272, PubMed:26479788). Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4 (PubMed:28525742). In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1) (PubMed:19818714). The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me) (PubMed:19818714). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). By monoubiquitinating histone H2B H2BC9/H2BJ and thereby promoting chromatin remodeling, positively regulates STAT1-dependent interferon-stimulated gene transcription and thus STAT1-mediated control of viral replication (PubMed:26479788). Independently of its catalytic activity, promotes the sorting of chemokine receptor CXCR4 from early endosome to lysosome following CXCL12 stimulation by reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination of endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:24790097). In addition, required for the recruitment of HGS and STAM to early endosomes (PubMed:24790097). In association with PARP9, plays a role in antiviral responses by mediating 'Lys-48'-linked ubiquitination of encephalomyocarditis virus (EMCV) and human rhinovirus (HRV) C3 proteases and thus promoting their proteasomal-mediated degradation (PubMed:26479788). {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}. |
| Q8TDF6 | RASGRP4 | S515 | ochoa | RAS guanyl-releasing protein 4 | Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP (PubMed:11880369, PubMed:11956218, PubMed:12493770, PubMed:18024961). In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway by promoting Ras-mediated activation of PIK3CG/PI3Kgamma to promote neutrophil functional responses (By similarity). In CD117(+) dendritic cells and mast cells, participates in an lipopolysaccharide (LPS)-activated signaling pathway that stimulates the production of interferon-gamma and other pro-inflammatory cytokines by natural killer (NK) cells (By similarity). May function in mast cell differentiation (PubMed:11880369, PubMed:11956218, PubMed:12493770, PubMed:18024961). Does not appear to be required for the development of B-cells, DC-cells, T-cells, or NK-cells (By similarity). {ECO:0000250|UniProtKB:Q8BTM9, ECO:0000269|PubMed:11880369, ECO:0000269|PubMed:11956218, ECO:0000269|PubMed:12493770, ECO:0000269|PubMed:18024961}. |
| Q8TDJ6 | DMXL2 | S2123 | ochoa | DmX-like protein 2 (Rabconnectin-3) | May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles (PubMed:11809763). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (By similarity). {ECO:0000250|UniProtKB:Q8BPN8, ECO:0000269|PubMed:11809763}. |
| Q8TEB1 | DCAF11 | S147 | ochoa | DDB1- and CUL4-associated factor 11 (WD repeat-containing protein 23) | May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240}. |
| Q8TF01 | PNISR | S726 | ochoa | Arginine/serine-rich protein PNISR (PNN-interacting serine/arginine-rich protein) (SR-related protein) (SR-rich protein) (Serine/arginine-rich-splicing regulatory protein 130) (SRrp130) (Splicing factor, arginine/serine-rich 130) (Splicing factor, arginine/serine-rich 18) | None |
| Q8WUA7 | TBC1D22A | S21 | ochoa | TBC1 domain family member 22A | May act as a GTPase-activating protein for Rab family protein(s). {ECO:0000250}. |
| Q8WUF5 | PPP1R13L | S134 | ochoa | RelA-associated inhibitor (Inhibitor of ASPP protein) (Protein iASPP) (NFkB-interacting protein 1) (PPP1R13B-like protein) | Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (PubMed:12524540). Is involved in NF-kappa-B dependent negative regulation of inflammatory response (PubMed:28069640). {ECO:0000269|PubMed:10336463, ECO:0000269|PubMed:12134007, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:15489900, ECO:0000269|PubMed:28069640}. |
| Q8WUH6 | TMEM263 | S23 | ochoa | Transmembrane protein 263 | May play a role in bone development. {ECO:0000269|PubMed:34238371}. |
| Q8WUI4 | HDAC7 | S464 | ochoa | Histone deacetylase 7 (HD7) (EC 3.5.1.98) (Histone deacetylase 7A) (HD7a) (Protein deacetylase HDAC7) (EC 3.5.1.-) | Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (By similarity). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C (By similarity). During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene (PubMed:12239305). Positively regulates the transcriptional repressor activity of FOXP3 (PubMed:17360565). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). Also acetylates non-histone proteins, such as ALKBH5 (PubMed:37369679). {ECO:0000250|UniProtKB:Q8C2B3, ECO:0000269|PubMed:12239305, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:37369679}. |
| Q8WUM0 | NUP133 | S1133 | ochoa | Nuclear pore complex protein Nup133 (133 kDa nucleoporin) (Nucleoporin Nup133) | Involved in poly(A)+ RNA transport. Involved in nephrogenesis (PubMed:30179222). {ECO:0000269|PubMed:11684705, ECO:0000269|PubMed:30179222}. |
| Q8WVB6 | CHTF18 | S92 | ochoa | Chromosome transmission fidelity protein 18 homolog (hCTF18) (CHL12) | Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated by the presence of primed DNA, replication protein A (RPA) and by proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. Interacts with and stimulates DNA polymerase POLH. During DNA repair synthesis, involved in loading DNA polymerase POLE at the sites of local damage (PubMed:20227374). {ECO:0000269|PubMed:12766176, ECO:0000269|PubMed:12930902, ECO:0000269|PubMed:17545166, ECO:0000269|PubMed:20227374}. |
| Q8WVM7 | STAG1 | S1142 | ochoa | Cohesin subunit SA-1 (SCC3 homolog 1) (Stromal antigen 1) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. |
| Q8WVV4 | POF1B | S156 | ochoa | Protein POF1B (Premature ovarian failure protein 1B) | Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development. {ECO:0000269|PubMed:16773570, ECO:0000269|PubMed:21940798}. |
| Q8WXE0 | CASKIN2 | S825 | ochoa | Caskin-2 (CASK-interacting protein 2) | None |
| Q8WXG6 | MADD | S230 | ochoa | MAP kinase-activating death domain protein (Differentially expressed in normal and neoplastic cells) (Insulinoma glucagonoma clone 20) (Rab3 GDP/GTP exchange factor) (RabGEF) (Rab3 GDP/GTP exchange protein) (Rab3GEP) | Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064). {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q80U28, ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:32761064, ECO:0000269|PubMed:9115275}. |
| Q8WZ75 | ROBO4 | S899 | ochoa | Roundabout homolog 4 (Magic roundabout) | Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins (By similarity). Involved in the maintenance of endothelial barrier organization and function (PubMed:30455415). {ECO:0000250, ECO:0000269|PubMed:30455415}. |
| Q92499 | DDX1 | S700 | ochoa | ATP-dependent RNA helicase DDX1 (EC 3.6.4.13) (DEAD box protein 1) (DEAD box protein retinoblastoma) (DBP-RB) | Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double-strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation. Acts as a positive transcriptional regulator of cyclin CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1. Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity). {ECO:0000250|UniProtKB:Q91VR5, ECO:0000269|PubMed:12183465, ECO:0000269|PubMed:15567440, ECO:0000269|PubMed:18335541, ECO:0000269|PubMed:18710941, ECO:0000269|PubMed:20573827, ECO:0000269|PubMed:24870230}.; FUNCTION: (Microbial infection) Required for HIV-1 Rev function as well as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence of HIV-1 mRNAs. {ECO:0000269|PubMed:15567440}.; FUNCTION: (Microbial infection) Required for Coronavirus IBV replication. {ECO:0000269|PubMed:20573827}. |
| Q92556 | ELMO1 | S344 | ochoa | Engulfment and cell motility protein 1 (Protein ced-12 homolog) | Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1. {ECO:0000269|PubMed:11595183, ECO:0000269|PubMed:12134158}. |
| Q92574 | TSC1 | S1080 | ochoa | Hamartin (Tuberous sclerosis 1 protein) | Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155). {ECO:0000250|UniProtKB:Q9Z136, ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:16464865, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:33215753, ECO:0000269|PubMed:9242607}. |
| Q92609 | TBC1D5 | S730 | ochoa | TBC1 domain family member 5 | May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity (PubMed:19531583, PubMed:20923837). Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy (PubMed:22354992). May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (PubMed:24603492). {ECO:0000269|PubMed:19531583, ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22354992, ECO:0000269|PubMed:24603492, ECO:0000305|PubMed:19531583, ECO:0000305|PubMed:22354992, ECO:0000305|PubMed:24603492}. |
| Q92613 | JADE3 | S703 | ochoa | Protein Jade-3 (Jade family PHD finger protein 3) (PHD finger protein 16) | Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. {ECO:0000269|PubMed:16387653}. |
| Q92619 | ARHGAP45 | S433 | ochoa | Rho GTPase-activating protein 45 [Cleaved into: Minor histocompatibility antigen HA-1 (mHag HA-1)] | Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity. {ECO:0000269|PubMed:24086303}.; FUNCTION: Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL. {ECO:0000269|PubMed:12601144, ECO:0000269|PubMed:8260714, ECO:0000269|PubMed:8532022, ECO:0000269|PubMed:9798702}. |
| Q92736 | RYR2 | S2368 | psp | Ryanodine receptor 2 (RYR-2) (RyR2) (hRYR-2) (Cardiac muscle ryanodine receptor) (Cardiac muscle ryanodine receptor-calcium release channel) (Type 2 ryanodine receptor) | Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development. {ECO:0000269|PubMed:10830164, ECO:0000269|PubMed:17984046, ECO:0000269|PubMed:20056922, ECO:0000269|PubMed:27733687, ECO:0000269|PubMed:33536282}. |
| Q92754 | TFAP2C | S22 | ochoa | Transcription factor AP-2 gamma (AP2-gamma) (Activating enhancer-binding protein 2 gamma) (Transcription factor ERF-1) | Sequence-specific DNA-binding transcription factor that interacts with cellular enhancer elements to regulate transcription of selected genes, and which plays a key role in early embryonic development (PubMed:11694877, PubMed:24413532). AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions (PubMed:11694877, PubMed:24413532). TFAP2C plays a key role in early embryonic development by regulating both inner cell mass (ICM) and trophectoderm differentiation (By similarity). At the 8-cell stage, during morula development, controls expression of cell-polarity genes (By similarity). Upon trophoblast commitment, binds to late trophectoderm genes in blastocysts together with CDX2, and later to extra-embryonic ectoderm genes together with SOX2 (By similarity). Binds to both closed and open chromatin with other transcription factors (By similarity). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532). {ECO:0000250|UniProtKB:Q61312, ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:24413532}. |
| Q92766 | RREB1 | S1107 | ochoa | Ras-responsive element-binding protein 1 (RREB-1) (Finger protein in nuclear bodies) (Raf-responsive zinc finger protein LZ321) (Zinc finger motif enhancer-binding protein 1) (Zep-1) | Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters (PubMed:10390538, PubMed:15067362, PubMed:17550981, PubMed:8816445, PubMed:9305772). Represses the angiotensinogen gene (PubMed:15067362). Negatively regulates the transcriptional activity of AR (PubMed:17550981). Potentiates the transcriptional activity of NEUROD1 (PubMed:12482979). Promotes brown adipocyte differentiation (By similarity). May be involved in Ras/Raf-mediated cell differentiation by enhancing calcitonin expression (PubMed:8816445). {ECO:0000250|UniProtKB:Q3UH06, ECO:0000269|PubMed:10390538, ECO:0000269|PubMed:12482979, ECO:0000269|PubMed:15067362, ECO:0000269|PubMed:17550981, ECO:0000269|PubMed:8816445, ECO:0000269|PubMed:9305772}. |
| Q92804 | TAF15 | S97 | ochoa | TATA-binding protein-associated factor 2N (68 kDa TATA-binding protein-associated factor) (TAF(II)68) (TAFII68) (RNA-binding protein 56) | RNA and ssDNA-binding protein that may play specific roles during transcription initiation at distinct promoters. Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Can enter the preinitiation complex together with the RNA polymerase II (Pol II). {ECO:0000269|PubMed:19124016, ECO:0000269|PubMed:21256132}. |
| Q92835 | INPP5D | S27 | psp | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (EC 3.1.3.86) (Inositol polyphosphate-5-phosphatase D) (EC 3.1.3.56) (Inositol polyphosphate-5-phosphatase of 145 kDa) (SIP-145) (Phosphatidylinositol 4,5-bisphosphate 5-phosphatase) (EC 3.1.3.36) (SH2 domain-containing inositol 5'-phosphatase 1) (SH2 domain-containing inositol phosphatase 1) (SHIP-1) (p150Ship) (hp51CN) | Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:10764818, PubMed:8723348, PubMed:8769125). Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (PubMed:10764818, PubMed:8769125, PubMed:9108392). Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity (PubMed:16682172). Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:12421919, ECO:0000269|PubMed:16682172, ECO:0000269|PubMed:8723348, ECO:0000269|PubMed:8769125, ECO:0000269|PubMed:9108392}. |
| Q92900 | UPF1 | S956 | ochoa | Regulator of nonsense transcripts 1 (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent helicase RENT1) (Nonsense mRNA reducing factor 1) (NORF1) (Up-frameshift suppressor 1 homolog) (hUpf1) | RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs (PubMed:11163187, PubMed:16086026, PubMed:18172165, PubMed:21145460, PubMed:21419344, PubMed:24726324). Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD (PubMed:11544179, PubMed:25220460). Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD (PubMed:21419344). Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors (PubMed:12554878). UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (PubMed:18447585). Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (PubMed:16086026, PubMed:18172165). For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585, PubMed:25220460). The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (PubMed:21145460). Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (By similarity). Also capable of unwinding double-stranded DNA and translocating on single-stranded DNA (PubMed:30218034). {ECO:0000250|UniProtKB:Q9EPU0, ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:12554878, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:18447585, ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:21145460, ECO:0000269|PubMed:21419344, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:25220460, ECO:0000269|PubMed:30218034}. |
| Q92904 | DAZL | S65 | psp | Deleted in azoospermia-like (DAZ homolog) (DAZ-like autosomal) (Deleted in azoospermia-like 1) (SPGY-like-autosomal) | RNA-binding protein, which is essential for gametogenesis in both males and females. Plays a central role during spermatogenesis. Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU triplets, and thereby regulating the translation of key transcripts (By similarity). {ECO:0000250}. |
| Q92994 | BRF1 | S410 | ochoa | Transcription factor IIIB 90 kDa subunit (TFIIIB90) (hTFIIIB90) (B-related factor 1) (BRF-1) (hBRF) (TAF3B2) (TATA box-binding protein-associated factor, RNA polymerase III, subunit 2) | General activator of RNA polymerase which utilizes different TFIIIB complexes at structurally distinct promoters. The isoform 1 is involved in the transcription of tRNA, adenovirus VA1, 7SL and 5S RNA. Isoform 2 is required for transcription of the U6 promoter. |
| Q93100 | PHKB | S231 | ochoa | Phosphorylase b kinase regulatory subunit beta (Phosphorylase kinase subunit beta) | Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation. |
| Q969G5 | CAVIN3 | S56 | ochoa | Caveolae-associated protein 3 (Cavin-3) (Protein kinase C delta-binding protein) (Serum deprivation response factor-related gene product that binds to C-kinase) (hSRBC) | Regulates the traffic and/or budding of caveolae (PubMed:19262564). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in smooth muscle but not in the lung and heart endothelial cells. Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by promoting the rapid release of caveolae from the cell surface. Plays a role in the regulation of the circadian clock. Modulates the period length and phase of circadian gene expression and also regulates expression and interaction of the core clock components PER1/2 and CRY1/2 (By similarity). {ECO:0000250|UniProtKB:Q91VJ2, ECO:0000250|UniProtKB:Q9Z1H9, ECO:0000269|PubMed:19262564}. |
| Q96A72 | MAGOHB | S108 | ochoa | Protein mago nashi homolog 2 | Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961, PubMed:30705154). Plays a redundant role with MAGOH in the exon junction complex and in the nonsense-mediated decay (NMD) pathway (PubMed:23917022). {ECO:0000269|PubMed:23917022, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:30705154}. |
| Q96BY6 | DOCK10 | S1322 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96CN7 | ISOC1 | S166 | ochoa | Isochorismatase domain-containing protein 1 | None |
| Q96CX2 | KCTD12 | S204 | ochoa | BTB/POZ domain-containing protein KCTD12 (Pfetin) (Predominantly fetal expressed T1 domain) | Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). {ECO:0000250}. |
| Q96D71 | REPS1 | S307 | ochoa | RalBP1-associated Eps domain-containing protein 1 (RalBP1-interacting protein 1) | May coordinate the cellular actions of activated EGF receptors and Ral-GTPases. {ECO:0000250}. |
| Q96E39 | RBMXL1 | S280 | ochoa | RNA binding motif protein, X-linked-like-1 (Heterogeneous nuclear ribonucleoprotein G-like 1) | RNA-binding protein which may be involved in pre-mRNA splicing. {ECO:0000250}. |
| Q96FV2 | SCRN2 | S55 | ochoa | Secernin-2 | None |
| Q96G42 | KLHDC7B | S517 | ochoa | Kelch domain-containing protein 7B | None |
| Q96HA1 | POM121 | S500 | ochoa | Nuclear envelope pore membrane protein POM 121 (Nuclear envelope pore membrane protein POM 121A) (Nucleoporin Nup121) (Pore membrane protein of 121 kDa) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| Q96ID5 | IGSF21 | S389 | ochoa | Immunoglobulin superfamily member 21 (IgSF21) | Involved in synaptic inhibition in the brain. Selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic NRXN2. {ECO:0000250|UniProtKB:Q7TNR6}. |
| Q96IF1 | AJUBA | S79 | ochoa | LIM domain-containing protein ajuba | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. {ECO:0000269|PubMed:12417594, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:15870274, ECO:0000269|PubMed:16413547, ECO:0000269|PubMed:17909014, ECO:0000269|PubMed:18805794, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:22286099}. |
| Q96JP5 | ZFP91 | S177 | ochoa | E3 ubiquitin-protein ligase ZFP91 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase ZFP91) (Zinc finger protein 757) (Zinc finger protein 91 homolog) (Zfp-91) | Atypical E3 ubiquitin-protein ligase that mediates 'Lys-63'-linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate MAP3K14/NIK. It thereby acts as an activator of the non-canonical NF-kappa-B2/NFKB2 pathway. May also play an important role in cell proliferation and/or anti-apoptosis. {ECO:0000269|PubMed:12738986, ECO:0000269|PubMed:20682767}. |
| Q96JQ0 | DCHS1 | S3035 | ochoa | Protocadherin-16 (Cadherin-19) (Cadherin-25) (Fibroblast cadherin-1) (Protein dachsous homolog 1) | Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, acting in the regulation of cell migration involved in valve formation (PubMed:26258302). {ECO:0000269|PubMed:26258302}. |
| Q96KP4 | CNDP2 | S58 | ochoa | Cytosolic non-specific dipeptidase (EC 3.4.13.18) (CNDP dipeptidase 2) (Glutamate carboxypeptidase-like protein 1) (Peptidase A) (Threonyl dipeptidase) | Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides (By similarity). Mediates threonyl dipeptide catabolism in a tissue-specific way (By similarity). Has high dipeptidase activity toward cysteinylglycine, an intermediate metabolite in glutathione metabolism (PubMed:12473676, PubMed:19346245). Metabolizes N-lactoyl-amino acids, both through hydrolysis to form lactic acid and amino acids, as well as through their formation by reverse proteolysis (PubMed:25964343). Plays a role in the regulation of cell cycle arrest and apoptosis (PubMed:17121880, PubMed:24395568). {ECO:0000250|UniProtKB:Q9D1A2, ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:17121880, ECO:0000269|PubMed:19346245, ECO:0000269|PubMed:24395568, ECO:0000269|PubMed:25964343}. |
| Q96KQ4 | PPP1R13B | S475 | ochoa | Apoptosis-stimulating of p53 protein 1 (Protein phosphatase 1 regulatory subunit 13B) | Regulator that plays a central role in regulation of apoptosis via its interaction with p53/TP53 (PubMed:11684014, PubMed:12524540). Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. {ECO:0000269|PubMed:11684014, ECO:0000269|PubMed:12524540}. |
| Q96KQ4 | PPP1R13B | S661 | ochoa | Apoptosis-stimulating of p53 protein 1 (Protein phosphatase 1 regulatory subunit 13B) | Regulator that plays a central role in regulation of apoptosis via its interaction with p53/TP53 (PubMed:11684014, PubMed:12524540). Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. {ECO:0000269|PubMed:11684014, ECO:0000269|PubMed:12524540}. |
| Q96L73 | NSD1 | S1077 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-36 specific (EC 2.1.1.357) (Androgen receptor coactivator 267 kDa protein) (Androgen receptor-associated protein of 267 kDa) (H3-K36-HMTase) (Lysine N-methyltransferase 3B) (Nuclear receptor-binding SET domain-containing protein 1) (NR-binding SET domain-containing protein) | Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. |
| Q96MU7 | YTHDC1 | S294 | ochoa | YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) | Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. |
| Q96MU7 | YTHDC1 | S326 | ochoa | YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) | Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. |
| Q96MX3 | ZNF48 | S316 | ochoa | Zinc finger protein 48 (Zinc finger protein 553) | May be involved in transcriptional regulation. |
| Q96N67 | DOCK7 | S414 | ochoa | Dedicator of cytokinesis protein 7 | Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}. |
| Q96N67 | DOCK7 | S1403 | ochoa | Dedicator of cytokinesis protein 7 | Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}. |
| Q96N96 | SPATA13 | S114 | ochoa | Spermatogenesis-associated protein 13 (APC-stimulated guanine nucleotide exchange factor 2) (Asef2) | Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Regulates cell migration and adhesion assembly and disassembly through a RAC1, PI3K, RHOA and AKT1-dependent mechanism. Increases both RAC1 and CDC42 activity, but decreases the amount of active RHOA. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression. {ECO:0000269|PubMed:17145773, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19151759, ECO:0000269|PubMed:19893577, ECO:0000269|PubMed:19934221}. |
| Q96PC5 | MIA2 | S1262 | ochoa | Melanoma inhibitory activity protein 2 (MIA protein 2) (CTAGE family member 5 ER export factor) (Cutaneous T-cell lymphoma-associated antigen 5) (Meningioma-expressed antigen 6/11) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum (PubMed:21525241, PubMed:25202031, PubMed:27138255, PubMed:27170179). Plays a role in the secretion of lipoproteins, pre-chylomicrons and pre-VLDLs, by participating in their export from the endoplasmic reticulum (PubMed:27138255). Thereby, may play a role in cholesterol and triglyceride homeostasis (By similarity). Required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers and recruiting PREB/SEC12 at the endoplasmic reticulum exit sites (PubMed:21525241, PubMed:25202031, PubMed:27170179). {ECO:0000250|UniProtKB:Q91ZV0, ECO:0000269|PubMed:21525241, ECO:0000269|PubMed:25202031, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:27170179}. |
| Q96PN7 | TRERF1 | S762 | ochoa | Transcriptional-regulating factor 1 (Breast cancer anti-estrogen resistance 2) (Transcriptional-regulating protein 132) (Zinc finger protein rapa) (Zinc finger transcription factor TReP-132) | Binds DNA and activates transcription of CYP11A1. Interaction with CREBBP and EP300 results in a synergistic transcriptional activation of CYP11A1. {ECO:0000269|PubMed:11349124, ECO:0000269|PubMed:16371131}. |
| Q96PU5 | NEDD4L | S795 | psp | E3 ubiquitin-protein ligase NEDD4-like (EC 2.3.2.26) (EC 2.3.2.36) (HECT-type E3 ubiquitin transferase NED4L) (NEDD4.2) (Nedd4-2) | E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:20064473, PubMed:31959741, PubMed:33608556). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556). Ubiquitinates TTYH2 and TTYH3 and regulates protein levels of TTYH2 (PubMed:18577513). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:18577513, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961, ECO:0000269|PubMed:33608556}. |
| Q96R06 | SPAG5 | S944 | ochoa | Sperm-associated antigen 5 (Astrin) (Deepest) (Mitotic spindle-associated protein p126) (MAP126) | Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457). {ECO:0000269|PubMed:12356910, ECO:0000269|PubMed:17664331, ECO:0000269|PubMed:18055457, ECO:0000269|PubMed:18361916, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:27462074, ECO:0000305|PubMed:11724960}. |
| Q96RL1 | UIMC1 | S241 | ochoa | BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) | Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}. |
| Q96RS0 | TGS1 | S445 | ochoa | Trimethylguanosine synthase (EC 2.1.1.-) (CLL-associated antigen KW-2) (Cap-specific guanine-N(2) methyltransferase) (Hepatocellular carcinoma-associated antigen 137) (Nuclear receptor coactivator 6-interacting protein) (PRIP-interacting protein with methyltransferase motif) (PIMT) (PIPMT) | Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation. {ECO:0000269|PubMed:11517327, ECO:0000269|PubMed:11912212, ECO:0000269|PubMed:16687569, ECO:0000269|PubMed:18775984}. |
| Q96RT6 | CTAGE1 | S623 | ochoa | cTAGE family member 2 (Protein cTAGE-2) (Cancer/testis antigen 21.2) (CT21.2) | None |
| Q96S38 | RPS6KC1 | S528 | ochoa | Ribosomal protein S6 kinase delta-1 (S6K-delta-1) (EC 2.7.11.1) (52 kDa ribosomal protein S6 kinase) (Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein) (SPHK1-binding protein) | May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell (PubMed:12077123). Plays a role in the recruitment of PRDX3 to early endosomes (PubMed:15750338). {ECO:0000269|PubMed:12077123, ECO:0000269|PubMed:15750338}. |
| Q96S38 | RPS6KC1 | S664 | ochoa | Ribosomal protein S6 kinase delta-1 (S6K-delta-1) (EC 2.7.11.1) (52 kDa ribosomal protein S6 kinase) (Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein) (SPHK1-binding protein) | May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell (PubMed:12077123). Plays a role in the recruitment of PRDX3 to early endosomes (PubMed:15750338). {ECO:0000269|PubMed:12077123, ECO:0000269|PubMed:15750338}. |
| Q96T23 | RSF1 | S1226 | ochoa | Remodeling and spacing factor 1 (Rsf-1) (HBV pX-associated protein 8) (Hepatitis B virus X-associated protein) (p325 subunit of RSF chromatin-remodeling complex) | Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF-alpha induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984). {ECO:0000269|PubMed:11788598, ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:28801535}. |
| Q99081 | TCF12 | S116 | ochoa | Transcription factor 12 (TCF-12) (Class B basic helix-loop-helix protein 20) (bHLHb20) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4) | Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (By similarity). May be involved in the functional network that regulates the development of the GnRH axis (PubMed:32620954). {ECO:0000250|UniProtKB:Q61286, ECO:0000269|PubMed:32620954}. |
| Q99460 | PSMD1 | S290 | ochoa | 26S proteasome non-ATPase regulatory subunit 1 (26S proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proteasome subunit p112) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}. |
| Q99541 | PLIN2 | S222 | ochoa | Perilipin-2 (Adipophilin) (Adipose differentiation-related protein) (ADRP) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets. {ECO:0000269|PubMed:34077757}. |
| Q99704 | DOK1 | S460 | ochoa | Docking protein 1 (Downstream of tyrosine kinase 1) (p62(dok)) (pp62) | DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3. {ECO:0000269|PubMed:18156175}. |
| Q99959 | PKP2 | S225 | ochoa | Plakophilin-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297). {ECO:0000250|UniProtKB:F1M7L9, ECO:0000250|UniProtKB:Q9CQ73, ECO:0000269|PubMed:18662195, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:22781308, ECO:0000269|PubMed:23884246, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:28169297, ECO:0000269|PubMed:34368962, ECO:0000269|PubMed:35959657}. |
| Q9BRJ6 | C7orf50 | S175 | ochoa | Protein cholesin | Hormone secreted from the intestine in response to cholesterol, where it acts to inhibit cholesterol synthesis in the liver and VLDL secretion,leading to a reduction in circulating cholesterol levels. Acts through binding to its receptor, GPR146. {ECO:0000269|PubMed:38503280}. |
| Q9BRS2 | RIOK1 | S89 | ochoa | Serine/threonine-protein kinase RIO1 (EC 2.7.11.1) (EC 3.6.1.-) (RIO kinase 1) | Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor (PubMed:22072790). The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit (By similarity). Despite the protein kinase domain is proposed to act predominantly as an ATPase (By similarity). The catalytic activity regulates its dynamic association with the 40S subunit (By similarity). In addition to its role in ribosomal biogenesis acts as an adapter protein by recruiting NCL/nucleolin the to PRMT5 complex for its symmetrical methylation (PubMed:21081503). {ECO:0000250|UniProtKB:G0S3J5, ECO:0000250|UniProtKB:Q12196, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:22072790}. |
| Q9BRX2 | PELO | S55 | ochoa | Protein pelota homolog (hPelota) (Protein Dom34 homolog) | Component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway (PubMed:21448132, PubMed:23667253, PubMed:27543824, PubMed:27863242). In the Pelota-HBS1L complex, PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel (PubMed:27543824, PubMed:27863242). Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132, PubMed:32006463). As part of the PINK1-regulated signaling, upon mitochondrial damage is recruited to the ribosome/mRNA-ribonucleoprotein complex associated to mitochondrial outer membrane thereby enabling the recruitment of autophagy receptors and induction of mitophagy (PubMed:29861391). {ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:23667253, ECO:0000269|PubMed:27543824, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:29861391, ECO:0000269|PubMed:32006463}. |
| Q9BRX2 | PELO | S58 | ochoa | Protein pelota homolog (hPelota) (Protein Dom34 homolog) | Component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway (PubMed:21448132, PubMed:23667253, PubMed:27543824, PubMed:27863242). In the Pelota-HBS1L complex, PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel (PubMed:27543824, PubMed:27863242). Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132, PubMed:32006463). As part of the PINK1-regulated signaling, upon mitochondrial damage is recruited to the ribosome/mRNA-ribonucleoprotein complex associated to mitochondrial outer membrane thereby enabling the recruitment of autophagy receptors and induction of mitophagy (PubMed:29861391). {ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:23667253, ECO:0000269|PubMed:27543824, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:29861391, ECO:0000269|PubMed:32006463}. |
| Q9BTC0 | DIDO1 | S114 | ochoa | Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) | Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}. |
| Q9BTE3 | MCMBP | S193 | ochoa | Mini-chromosome maintenance complex-binding protein (MCM-BP) (MCM-binding protein) | Associated component of the MCM complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion. {ECO:0000269|PubMed:20090939, ECO:0000269|PubMed:21196493}. |
| Q9BU76 | MMTAG2 | S123 | ochoa | Multiple myeloma tumor-associated protein 2 (hMMTAG2) | None |
| Q9BU76 | MMTAG2 | S127 | ochoa | Multiple myeloma tumor-associated protein 2 (hMMTAG2) | None |
| Q9BUF5 | TUBB6 | S278 | ochoa | Tubulin beta-6 chain (Tubulin beta class V) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}. |
| Q9BV36 | MLPH | S574 | ochoa | Melanophilin (Exophilin-3) (Slp homolog lacking C2 domains a) (SlaC2-a) (Synaptotagmin-like protein 2a) | Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}. |
| Q9BVA1 | TUBB2B | S278 | ochoa | Tubulin beta-2B chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:23001566, PubMed:26732629, PubMed:28013290). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910). {ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:23001566, ECO:0000269|PubMed:26732629, ECO:0000269|PubMed:28013290}. |
| Q9BVJ6 | UTP14A | S445 | ochoa | U3 small nucleolar RNA-associated protein 14 homolog A (Antigen NY-CO-16) (Serologically defined colon cancer antigen 16) | May be required for ribosome biogenesis. {ECO:0000250}. |
| Q9BVS4 | RIOK2 | S442 | ochoa | Serine/threonine-protein kinase RIO2 (EC 2.7.11.1) (RIO kinase 2) | Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in export of the 40S pre-ribosome particles (pre-40S) from the nucleus to the cytoplasm. Its kinase activity is required for the release of NOB1, PNO1 and LTV1 from the late pre-40S and the processing of 18S-E pre-rRNA to the mature 18S rRNA (PubMed:19564402). Regulates the timing of the metaphase-anaphase transition during mitotic progression, and its phosphorylation, most likely by PLK1, regulates this function (PubMed:21880710). {ECO:0000269|PubMed:16037817, ECO:0000269|PubMed:19564402, ECO:0000269|PubMed:21880710}. |
| Q9BWT1 | CDCA7 | S142 | ochoa | Cell division cycle-associated protein 7 (Protein JPO1) | Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. May play a role as transcriptional regulator. {ECO:0000269|PubMed:11598121, ECO:0000269|PubMed:15994934, ECO:0000269|PubMed:16580749, ECO:0000269|PubMed:23166294}. |
| Q9BXM7 | PINK1 | S228 | psp | Serine/threonine-protein kinase PINK1, mitochondrial (EC 2.7.11.1) (BRPK) (PTEN-induced putative kinase protein 1) | Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. It phosphorylates mitochondrial proteins to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:18957282, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20547144, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:24898855, PubMed:25527291, PubMed:32484300). Depending on the severity of mitochondrial damage, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN-dependent mitophagy (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23933751, PubMed:24898855, PubMed:32047033, PubMed:32484300). When cellular stress results in irreversible mitochondrial damage, PINK1 accumulates at the outer mitochondrial membrane (OMM) where it phosphorylates pre-existing polyubiquitin chains at 'Ser-65', recruits PRKN from the cytosol to the OMM and activates PRKN by phosphorylation at 'Ser-65'; activated PRKN then ubiquinates VDAC1 and other OMM proteins to initiate mitophagy (PubMed:14607334, PubMed:15087508, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291, PubMed:32047033). The PINK1-PRKN pathway also promotes fission of damaged mitochondria through phosphorylation and PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128). {ECO:0000250|UniProtKB:Q99MQ3, ECO:0000269|PubMed:14607334, ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:18443288, ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20547144, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:24898855, ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:29123128, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:32484300}. |
| Q9BYG4 | PARD6G | S110 | ochoa | Partitioning defective 6 homolog gamma (PAR-6 gamma) (PAR6D) | Adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (By similarity). {ECO:0000250}. |
| Q9BYG5 | PARD6B | S177 | ochoa | Partitioning defective 6 homolog beta (PAR-6 beta) (PAR-6B) | Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. |
| Q9C0B0 | UNK | S411 | ochoa | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9C0B0 | UNK | S611 | psp | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9C0B1 | FTO | S183 | ochoa | Alpha-ketoglutarate-dependent dioxygenase FTO (Fat mass and obesity-associated protein) (U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO) (EC 1.14.11.-) (U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO) (EC 1.14.11.-) (mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO) (m6A(m)-demethylase FTO) (EC 1.14.11.-) (mRNA N(6)-methyladenosine demethylase FTO) (EC 1.14.11.53) (tRNA N1-methyl adenine demethylase FTO) (EC 1.14.11.-) | RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:28002401, PubMed:30197295). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:30197295). M6A demethylation by FTO affects mRNA expression and stability (PubMed:30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:30197295). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:30197295). Has no activity towards 1-methylguanine (PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:18775698, PubMed:20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:28017614, PubMed:29249359). {ECO:0000250|UniProtKB:Q8BGW1, ECO:0000269|PubMed:18775698, ECO:0000269|PubMed:20376003, ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:25452335, ECO:0000269|PubMed:26287746, ECO:0000269|PubMed:26457839, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:28002401, ECO:0000269|PubMed:28017614, ECO:0000269|PubMed:29249359, ECO:0000269|PubMed:30197295}. |
| Q9C0C2 | TNKS1BP1 | S194 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1073 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C9 | UBE2O | S381 | ochoa | (E3-independent) E2 ubiquitin-conjugating enzyme (EC 2.3.2.24) (E2/E3 hybrid ubiquitin-protein ligase UBE2O) (Ubiquitin carrier protein O) (Ubiquitin-conjugating enzyme E2 O) (Ubiquitin-conjugating enzyme E2 of 230 kDa) (Ubiquitin-conjugating enzyme E2-230K) (Ubiquitin-protein ligase O) | E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). {ECO:0000269|PubMed:23381138, ECO:0000269|PubMed:23452853, ECO:0000269|PubMed:23455153, ECO:0000269|PubMed:24703950}. |
| Q9C0D5 | TANC1 | S280 | ochoa | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9C0G0 | ZNF407 | S937 | ochoa | Zinc finger protein 407 | May be involved in transcriptional regulation. |
| Q9GZR2 | REXO4 | S96 | ochoa | RNA exonuclease 4 (EC 3.1.-.-) (Exonuclease XPMC2) (Prevents mitotic catastrophe 2 protein homolog) (hPMC2) | None |
| Q9GZR2 | REXO4 | S131 | ochoa | RNA exonuclease 4 (EC 3.1.-.-) (Exonuclease XPMC2) (Prevents mitotic catastrophe 2 protein homolog) (hPMC2) | None |
| Q9GZY6 | LAT2 | S106 | ochoa | Linker for activation of T-cells family member 2 (Linker for activation of B-cells) (Membrane-associated adapter molecule) (Non-T-cell activation linker) (Williams-Beuren syndrome chromosomal region 15 protein) (Williams-Beuren syndrome chromosomal region 5 protein) | Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2. {ECO:0000269|PubMed:12486104, ECO:0000269|PubMed:12514734, ECO:0000269|PubMed:15010370}. |
| Q9H0B6 | KLC2 | S539 | ochoa | Kinesin light chain 2 (KLC 2) | Kinesin is a microtubule-associated force-producing protein that plays a role in organelle transport. The light chain functions in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (Probable). Through binding with PLEKHM2 and ARL8B, recruits kinesin-1 to lysosomes and hence direct lysosomes movement toward microtubule plus ends (PubMed:22172677). {ECO:0000269|PubMed:22172677, ECO:0000305|PubMed:22172677}. |
| Q9H0E9 | BRD8 | S383 | ochoa | Bromodomain-containing protein 8 (Skeletal muscle abundant protein) (Skeletal muscle abundant protein 2) (Thyroid hormone receptor coactivating protein of 120 kDa) (TrCP120) (p120) | May act as a coactivator during transcriptional activation by hormone-activated nuclear receptors (NR). Isoform 2 stimulates transcriptional activation by AR/DHTR, ESR1/NR3A1, RXRA/NR2B1 and THRB/ERBA2. At least isoform 1 and isoform 2 are components of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. {ECO:0000269|PubMed:10517671, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:24463511}. |
| Q9H0E9 | BRD8 | S590 | ochoa | Bromodomain-containing protein 8 (Skeletal muscle abundant protein) (Skeletal muscle abundant protein 2) (Thyroid hormone receptor coactivating protein of 120 kDa) (TrCP120) (p120) | May act as a coactivator during transcriptional activation by hormone-activated nuclear receptors (NR). Isoform 2 stimulates transcriptional activation by AR/DHTR, ESR1/NR3A1, RXRA/NR2B1 and THRB/ERBA2. At least isoform 1 and isoform 2 are components of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. {ECO:0000269|PubMed:10517671, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:24463511}. |
| Q9H0H5 | RACGAP1 | S206 | ochoa | Rac GTPase-activating protein 1 (Male germ cell RacGap) (MgcRacGAP) (Protein CYK4 homolog) (CYK4) (HsCYK-4) | Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Sequentially binds to ECT2 and RAB11FIP3 which regulates cleavage furrow ingression and abscission during cytokinesis (PubMed:18511905). Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity (PubMed:10979956). Has a critical role in erythropoiesis (PubMed:34818416). Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}. |
| Q9H1J1 | UPF3A | S401 | ochoa | Regulator of nonsense transcripts 3A (Nonsense mRNA reducing factor 3A) (Up-frameshift suppressor 3 homolog A) (hUpf3) | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. However, UPF3A is shown to be only marginally active in NMD as compared to UPF3B. Binds spliced mRNA upstream of exon-exon junctions. In vitro, weakly stimulates translation. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:16601204}. |
| Q9H1R3 | MYLK2 | S120 | ochoa | Myosin light chain kinase 2, skeletal/cardiac muscle (MLCK2) (EC 2.7.11.18) | Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain. {ECO:0000269|PubMed:11733062}. |
| Q9H2Y7 | ZNF106 | S1349 | ochoa | Zinc finger protein 106 (Zfp-106) (Zinc finger protein 474) | RNA-binding protein. Specifically binds to 5'-GGGGCC-3' sequence repeats in RNA. Essential for maintenance of peripheral motor neuron and skeletal muscle function. Required for normal expression and/or alternative splicing of a number of genes in spinal cord and skeletal muscle, including the neurite outgrowth inhibitor RTN4. Also contributes to normal mitochondrial respiratory function in motor neurons, via an unknown mechanism. {ECO:0000250|UniProtKB:O88466}. |
| Q9H4A6 | GOLPH3 | S35 | ochoa | Golgi phosphoprotein 3 (Coat protein GPP34) (Mitochondrial DNA absence factor) (MIDAS) | Phosphatidylinositol-4-phosphate-binding protein that links Golgi membranes to the cytoskeleton and may participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus. May also bind to the coatomer to regulate Golgi membrane trafficking. May play a role in anterograde transport from the Golgi to the plasma membrane and regulate secretion. Has also been involved in the control of the localization of Golgi enzymes through interaction with their cytoplasmic part. May play an indirect role in cell migration. Has also been involved in the modulation of mTOR signaling. May also be involved in the regulation of mitochondrial lipids biosynthesis. {ECO:0000269|PubMed:16263763, ECO:0000269|PubMed:19553991, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:22745132, ECO:0000269|PubMed:23027862, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:23500462}. |
| Q9H5I5 | PIEZO2 | S1844 | ochoa | Piezo-type mechanosensitive ion channel component 2 (Protein FAM38B) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). {ECO:0000250|UniProtKB:Q8CD54, ECO:0000269|PubMed:33057202, ECO:0000269|PubMed:37590348}. |
| Q9H5I5 | PIEZO2 | S1868 | ochoa | Piezo-type mechanosensitive ion channel component 2 (Protein FAM38B) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). {ECO:0000250|UniProtKB:Q8CD54, ECO:0000269|PubMed:33057202, ECO:0000269|PubMed:37590348}. |
| Q9H845 | ACAD9 | S187 | ochoa | Complex I assembly factor ACAD9, mitochondrial (Acyl-CoA dehydrogenase family member 9) (ACAD-9) (EC 1.3.8.-) | As part of the MCIA complex, primarily participates in the assembly of the mitochondrial complex I and therefore plays a role in oxidative phosphorylation (PubMed:20816094, PubMed:24158852, PubMed:32320651). This moonlighting protein also has a dehydrogenase activity toward a broad range of substrates with greater specificity for long-chain unsaturated acyl-CoAs (PubMed:12359260, PubMed:16020546, PubMed:21237683, PubMed:24158852). However, in vivo, it does not seem to play a primary role in fatty acid oxidation (PubMed:20816094, PubMed:24158852). In addition, the function in complex I assembly is independent of the dehydrogenase activity of the protein (PubMed:24158852). {ECO:0000269|PubMed:12359260, ECO:0000269|PubMed:16020546, ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:24158852, ECO:0000269|PubMed:32320651}. |
| Q9H8V3 | ECT2 | S415 | ochoa | Protein ECT2 (Epithelial cell-transforming sequence 2 oncogene) | Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}. |
| Q9HAU0 | PLEKHA5 | S549 | ochoa | Pleckstrin homology domain-containing family A member 5 (PH domain-containing family A member 5) (Phosphoinositol 3-phosphate-binding protein 2) (PEPP-2) | None |
| Q9HBA0 | TRPV4 | S162 | psp | Transient receptor potential cation channel subfamily V member 4 (TrpV4) (Osm-9-like TRP channel 4) (OTRPC4) (Transient receptor potential protein 12) (TRP12) (Vanilloid receptor-like channel 2) (Vanilloid receptor-like protein 2) (VRL-2) (Vanilloid receptor-related osmotically-activated channel) (VR-OAC) | Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:22526352, PubMed:23136043, PubMed:29899501). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18695040, PubMed:18826956, PubMed:29899501). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:20037586, PubMed:21964574, PubMed:25256292). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (PubMed:29899501). In neurons of the central nervous system, could play a role in triggering voluntary water intake in response to increased sodium concentration in body fluid (By similarity). {ECO:0000250|UniProtKB:Q9EPK8, ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:18587396, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956, ECO:0000269|PubMed:19759329, ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:23136043, ECO:0000269|PubMed:25256292, ECO:0000269|PubMed:26249260, ECO:0000269|PubMed:29899501}.; FUNCTION: [Isoform 1]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 5]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 2]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 4]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 6]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}. |
| Q9HBX9 | RXFP1 | S304 | ochoa | Relaxin receptor 1 (Leucine-rich repeat-containing G-protein coupled receptor 7) (Relaxin family peptide receptor 1) | Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP. |
| Q9HCE0 | EPG5 | S1589 | ochoa | Ectopic P granules protein 5 homolog | Involved in autophagy. May play a role in a late step of autophagy, such as clearance of autophagosomal cargo. Plays a key role in innate and adaptive immune response triggered by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides from pathogens, and mediated by the nucleotide-sensing receptor TLR9. It is necessary for the translocation of CpG dinucleotides from early endosomes to late endosomes and lysosomes, where TLR9 is located (PubMed:29130391). {ECO:0000269|PubMed:20550938, ECO:0000269|PubMed:23222957, ECO:0000269|PubMed:29130391}. |
| Q9HCE6 | ARHGEF10L | S1256 | ochoa | Rho guanine nucleotide exchange factor 10-like protein (GrinchGEF) | Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC. {ECO:0000269|PubMed:16112081}. |
| Q9HCS7 | XAB2 | S751 | ochoa | Pre-mRNA-splicing factor SYF1 (Protein HCNP) (XPA-binding protein 2) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). Involved in transcription-coupled repair (TCR), transcription and pre-mRNA splicing (PubMed:10944529, PubMed:17981804). {ECO:0000269|PubMed:10944529, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:17981804, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}. |
| Q9HCU4 | CELSR2 | S2665 | ochoa | Cadherin EGF LAG seven-pass G-type receptor 2 (Cadherin family member 10) (Epidermal growth factor-like protein 2) (EGF-like protein 2) (Flamingo homolog 3) (Multiple epidermal growth factor-like domains protein 3) (Multiple EGF-like domains protein 3) | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| Q9NP79 | VTA1 | S281 | ochoa | Vacuolar protein sorting-associated protein VTA1 homolog (Dopamine-responsive gene 1 protein) (DRG-1) (LYST-interacting protein 5) (LIP5) (SKD1-binding protein 1) (SBP1) | Involved in the endosomal multivesicular bodies (MVB) pathway. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. Thought to be a cofactor of VPS4A/B, which catalyzes disassembles membrane-associated ESCRT-III assemblies. Involved in the sorting and down-regulation of EGFR (By similarity). Involved in HIV-1 budding. {ECO:0000250, ECO:0000269|PubMed:15644320}. |
| Q9NPD3 | EXOSC4 | S61 | ochoa | Exosome complex component RRP41 (Exosome component 4) (Ribosomal RNA-processing protein 41) (p12A) | Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC4 binds to ARE-containing RNAs. {ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:20368444, ECO:0000269|PubMed:21255825}. |
| Q9NQ39 | RPS10P5 | S76 | ochoa | Putative ribosomal protein eS10-like (Putative 40S ribosomal protein S10-like) | None |
| Q9NQT8 | KIF13B | S732 | ochoa | Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) | Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes. {ECO:0000269|PubMed:20194617}. |
| Q9NRF2 | SH2B1 | S165 | psp | SH2B adapter protein 1 (Pro-rich, PH and SH2 domain-containing signaling mediator) (PSM) (SH2 domain-containing protein 1B) | Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor 1 (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as a positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF1 and PDGF-induced mitogenesis (By similarity). {ECO:0000250|UniProtKB:Q91ZM2, ECO:0000269|PubMed:11827956, ECO:0000269|PubMed:14565960, ECO:0000269|PubMed:15767667, ECO:0000269|PubMed:16569669, ECO:0000269|PubMed:17471236, ECO:0000269|PubMed:9694882, ECO:0000269|PubMed:9742218}. |
| Q9NS61 | KCNIP2 | S19 | ochoa | A-type potassium channel modulatory protein KCNIP2 (Cardiac voltage-gated potassium channel modulatory subunit) (Kv channel-interacting protein 2) (KChIP2) (Potassium channel-interacting protein 2) | Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels (PubMed:10676964, PubMed:11287421, PubMed:11684073, PubMed:12297301, PubMed:14623880, PubMed:34997220). Modulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner (PubMed:10676964, PubMed:11287421, PubMed:11684073, PubMed:12297301, PubMed:14623880, PubMed:34997220). Involved in KCND2 and KCND3 trafficking to the cell surface (PubMed:12829703). May be required for the expression of I(To) currents in the heart (By similarity). {ECO:0000250|UniProtKB:Q9JJ69, ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11287421, ECO:0000269|PubMed:11684073, ECO:0000269|PubMed:12297301, ECO:0000269|PubMed:12829703, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:34997220}. |
| Q9NS62 | THSD1 | S477 | ochoa | Thrombospondin type-1 domain-containing protein 1 (Transmembrane molecule with thrombospondin module) | Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix. {ECO:0000269|PubMed:27895300, ECO:0000269|PubMed:29069646}. |
| Q9NUL7 | DDX28 | S127 | ochoa | Probable ATP-dependent RNA helicase DDX28 (EC 3.6.4.13) (Mitochondrial DEAD box protein 28) | Plays an essential role in facilitating the proper assembly of the mitochondrial large ribosomal subunit and its helicase activity is essential for this function (PubMed:25683708, PubMed:25683715). May be involved in RNA processing or transport. Has RNA and Mg(2+)-dependent ATPase activity (PubMed:11350955). {ECO:0000269|PubMed:11350955, ECO:0000269|PubMed:25683708, ECO:0000269|PubMed:25683715}. |
| Q9NUQ6 | SPATS2L | S526 | ochoa | SPATS2-like protein (DNA polymerase-transactivated protein 6) (Stress granule and nucleolar protein) (SGNP) | None |
| Q9NWH9 | SLTM | S217 | ochoa | SAFB-like transcription modulator (Modulator of estrogen-induced transcription) | When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. {ECO:0000250}. |
| Q9NWH9 | SLTM | S944 | ochoa | SAFB-like transcription modulator (Modulator of estrogen-induced transcription) | When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. {ECO:0000250}. |
| Q9NWV8 | BABAM1 | S47 | ochoa | BRISC and BRCA1-A complex member 1 (Mediator of RAP80 interactions and targeting subunit of 40 kDa) (New component of the BRCA1-A complex) | Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). {ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749}. |
| Q9NX95 | SYBU | S125 | ochoa | Syntabulin (Golgi-localized syntaphilin-related protein) (Syntaxin-1-binding protein) | Part of a kinesin motor-adapter complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development. {ECO:0000250, ECO:0000269|PubMed:15459722}. |
| Q9NY59 | SMPD3 | S203 | ochoa | Sphingomyelin phosphodiesterase 3 (EC 3.1.4.12) (Neutral sphingomyelinase 2) (nSMase-2) (nSMase2) (Neutral sphingomyelinase II) | Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization (PubMed:10823942, PubMed:14741383, PubMed:15051724). Binds to anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) that modulate enzymatic activity and subcellular location. May be involved in IL-1-beta-induced JNK activation in hepatocytes (By similarity). May act as a mediator in transcriptional regulation of NOS2/iNOS via the NF-kappa-B activation under inflammatory conditions (By similarity). {ECO:0000250|UniProtKB:O35049, ECO:0000250|UniProtKB:Q9JJY3, ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:14741383, ECO:0000269|PubMed:15051724}. |
| Q9NY61 | AATF | S55 | ochoa | Protein AATF (Apoptosis-antagonizing transcription factor) (Rb-binding protein Che-1) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). May function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date. {ECO:0000269|PubMed:12450794, ECO:0000269|PubMed:12847090, ECO:0000269|PubMed:14627703, ECO:0000269|PubMed:15207272, ECO:0000269|PubMed:34516797}. |
| Q9NZ43 | USE1 | S146 | ochoa | Vesicle transport protein USE1 (Putative MAPK-activating protein PM26) (USE1-like protein) (p31) | SNARE that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER. {ECO:0000269|PubMed:15272311}. |
| Q9NZ56 | FMN2 | S93 | ochoa | Formin-2 | Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:21730168, PubMed:22330775). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:21730168, PubMed:22330775). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis (By similarity). Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest (PubMed:23375502). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). Protects cells against apoptosis by protecting CDKN1A against degradation (PubMed:23375502). {ECO:0000250|UniProtKB:Q9JL04, ECO:0000269|PubMed:21730168, ECO:0000269|PubMed:22330775, ECO:0000269|PubMed:23375502, ECO:0000269|PubMed:26287480}. |
| Q9NZ56 | FMN2 | S499 | ochoa | Formin-2 | Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:21730168, PubMed:22330775). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:21730168, PubMed:22330775). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis (By similarity). Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest (PubMed:23375502). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). Protects cells against apoptosis by protecting CDKN1A against degradation (PubMed:23375502). {ECO:0000250|UniProtKB:Q9JL04, ECO:0000269|PubMed:21730168, ECO:0000269|PubMed:22330775, ECO:0000269|PubMed:23375502, ECO:0000269|PubMed:26287480}. |
| Q9NZB2 | FAM120A | S1048 | ochoa | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q9NZH0 | GPRC5B | S354 | ochoa | G-protein coupled receptor family C group 5 member B (A-69G12.1) (Retinoic acid-induced gene 2 protein) (RAIG-2) | G-protein coupled receptor involved in the regulation of cell volume. {ECO:0000269|PubMed:37143309}. |
| Q9NZM3 | ITSN2 | S957 | ochoa | Intersectin-2 (SH3 domain-containing protein 1B) (SH3P18) (SH3P18-like WASP-associated protein) | Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:23999003}. |
| Q9P206 | NHSL3 | S409 | ochoa | NHS-like protein 3 | Able to directly activate the TNF-NFkappaB signaling pathway. {ECO:0000269|PubMed:32854746}. |
| Q9P275 | USP36 | S825 | ochoa | Ubiquitin carboxyl-terminal hydrolase 36 (EC 2.3.2.-) (EC 3.4.19.12) (Deubiquitinating enzyme 36) (Ubiquitin thioesterase 36) (Ubiquitin-specific-processing protease 36) | Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:19208757, PubMed:22902402, PubMed:29273634). Required for cell and organism viability (PubMed:19208757, PubMed:22902402, PubMed:29273634). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:19208757, PubMed:22902402, PubMed:29273634, PubMed:36912080). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368). Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing (PubMed:36912080). Binds to pre-rRNAs (PubMed:36912080). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341, ECO:0000269|PubMed:35989368, ECO:0000269|PubMed:36912080}. |
| Q9P2N7 | KLHL13 | S50 | ochoa | Kelch-like protein 13 (BTB and kelch domain-containing protein 2) | Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:19995937}. |
| Q9UBB9 | TFIP11 | S144 | ochoa | Tuftelin-interacting protein 11 (Septin and tuftelin-interacting protein 1) (STIP-1) | Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events. Intron turnover seems to proceed through reactions in two lariat-intron associated complexes termed Intron Large (IL) and Intron Small (IS). In cooperation with DHX15 seems to mediate the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns. May play a role in the differentiation of ameloblasts and odontoblasts or in the forming of the enamel extracellular matrix. {ECO:0000269|PubMed:19103666}. |
| Q9UBC2 | EPS15L1 | S672 | ochoa | Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) | Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}. |
| Q9UBC3 | DNMT3B | S82 | ochoa | DNA (cytosine-5)-methyltransferase 3B (Dnmt3b) (EC 2.1.1.37) (DNA methyltransferase HsaIIIB) (DNA MTase HsaIIIB) (M.HsaIIIB) | Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Functions as a transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells (PubMed:27153398). {ECO:0000250, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:17303076, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18567530, ECO:0000269|PubMed:27153398}. |
| Q9UBL3 | ASH2L | S101 | ochoa | Set1/Ash2 histone methyltransferase complex subunit ASH2 (ASH2-like protein) | Transcriptional regulator (PubMed:12670868). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated (PubMed:19556245). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). May play a role in hematopoiesis (PubMed:12670868). In association with RBBP5 and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}. |
| Q9UBL3 | ASH2L | S291 | ochoa | Set1/Ash2 histone methyltransferase complex subunit ASH2 (ASH2-like protein) | Transcriptional regulator (PubMed:12670868). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated (PubMed:19556245). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). May play a role in hematopoiesis (PubMed:12670868). In association with RBBP5 and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}. |
| Q9UBX3 | SLC25A10 | S93 | ochoa | Mitochondrial dicarboxylate carrier (DIC) (Solute carrier family 25 member 10) | Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across mitochondrial inner membrane (PubMed:29211846). Plays an important role in gluconeogenesis, fatty acid metabolism, urea synthesis, and sulfur metabolism, particularly in liver, by supplying the substrates for the different metabolic processes. Regulates fatty acid release from adipocytes, and contributes to systemic insulin sensitivity (By similarity). {ECO:0000250|UniProtKB:Q9QZD8, ECO:0000269|PubMed:29211846}. |
| Q9UER7 | DAXX | S184 | psp | Death domain-associated protein 6 (Daxx) (hDaxx) (ETS1-associated protein 1) (EAP1) (Fas death domain-associated protein) | Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as a histone chaperone that facilitates deposition of histone H3.3. Acts as a targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upon neuronal activation associates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV). Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (PubMed:15016915). {ECO:0000269|PubMed:12140263, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:17942542, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:24530302}. |
| Q9UFC0 | LRWD1 | S267 | ochoa | Leucine-rich repeat and WD repeat-containing protein 1 (Centromere protein 33) (CENP-33) (Origin recognition complex-associated protein) (ORC-associated protein) (ORCA) | Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability. {ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:20932478, ECO:0000269|PubMed:21029866, ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22645314}. |
| Q9UGU0 | TCF20 | S859 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UGU0 | TCF20 | S1482 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UHC1 | MLH3 | S753 | ochoa | DNA mismatch repair protein Mlh3 (MutL protein homolog 3) | Probably involved in the repair of mismatches in DNA. |
| Q9UHC7 | MKRN1 | S379 | ochoa | E3 ubiquitin-protein ligase makorin-1 (EC 2.3.2.27) (RING finger protein 61) (RING-type E3 ubiquitin transferase makorin-1) | E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by suppressing p53/TP53 under normal conditions, but stimulates apoptosis by repressing CDKN1A under stress conditions. Acts as a negative regulator of telomerase. Has negative and positive effects on RNA polymerase II-dependent transcription. {ECO:0000269|PubMed:16785614, ECO:0000269|PubMed:19536131}. |
| Q9UHV5 | RAPGEFL1 | S313 | ochoa | Rap guanine nucleotide exchange factor-like 1 (Link guanine nucleotide exchange factor II) (Link GEFII) | Probable guanine nucleotide exchange factor (GEF). |
| Q9UHV7 | MED13 | S1033 | ochoa | Mediator of RNA polymerase II transcription subunit 13 (Activator-recruited cofactor 250 kDa component) (ARC250) (Mediator complex subunit 13) (Thyroid hormone receptor-associated protein 1) (Thyroid hormone receptor-associated protein complex 240 kDa component) (Trap240) (Vitamin D3 receptor-interacting protein complex component DRIP250) (DRIP250) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269|PubMed:16595664}. |
| Q9UJD0 | RIMS3 | S111 | ochoa | Regulating synaptic membrane exocytosis protein 3 (Nim3) (RIM3 gamma) (Rab-3-interacting molecule 3) (RIM 3) | Regulates synaptic membrane exocytosis. {ECO:0000250}. |
| Q9UJF2 | RASAL2 | S916 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UJV8 | PURG | S163 | ochoa | Purine-rich element-binding protein gamma (Purine-rich element-binding protein G) | None |
| Q9UKA4 | AKAP11 | S1526 | ochoa | A-kinase anchor protein 11 (AKAP-11) (A-kinase anchor protein 220 kDa) (AKAP 220) (hAKAP220) (Protein kinase A-anchoring protein 11) (PRKA11) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them. |
| Q9UKG1 | APPL1 | S430 | psp | DCC-interacting protein 13-alpha (Dip13-alpha) (Adapter protein containing PH domain, PTB domain and leucine zipper motif 1) | Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:10490823, PubMed:15016378, PubMed:19661063, PubMed:26073777, PubMed:26583432). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (PubMed:15016378). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (By similarity). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (By similarity). Regulates TLR4 signaling in activated macrophages (By similarity). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (PubMed:19661063, PubMed:24879834, PubMed:26073777). Required for fibroblast migration through HGF cell signaling (By similarity). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (PubMed:19433865). {ECO:0000250|UniProtKB:Q8K3H0, ECO:0000269|PubMed:10490823, ECO:0000269|PubMed:15016378, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:19661063, ECO:0000269|PubMed:24879834, ECO:0000269|PubMed:26073777, ECO:0000269|PubMed:26583432}. |
| Q9UKY1 | ZHX1 | S156 | ochoa | Zinc fingers and homeoboxes protein 1 | Acts as a transcriptional repressor. Increases DNMT3B-mediated repressive transcriptional activity when DNMT3B is tethered to DNA. May link molecule between DNMT3B and other co-repressor proteins. {ECO:0000269|PubMed:12237128}. |
| Q9ULS5 | TMCC3 | S216 | ochoa | Transmembrane and coiled-coil domain protein 3 | None |
| Q9UMD9 | COL17A1 | S70 | ochoa | Collagen alpha-1(XVII) chain (180 kDa bullous pemphigoid antigen 2) (Bullous pemphigoid antigen 2) [Cleaved into: 120 kDa linear IgA disease antigen (120 kDa linear IgA dermatosis antigen) (Linear IgA disease antigen 1) (LAD-1); 97 kDa linear IgA disease antigen (97 kDa linear IgA bullous dermatosis antigen) (97 kDa LAD antigen) (97-LAD) (Linear IgA bullous disease antigen of 97 kDa) (LABD97)] | May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.; FUNCTION: The 120 kDa linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion. Is the target of linear IgA bullous dermatosis autoantibodies. |
| Q9UMS6 | SYNPO2 | S155 | ochoa | Synaptopodin-2 (Genethonin-2) (Myopodin) | Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}. |
| Q9UMZ2 | SYNRG | S469 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UPA5 | BSN | S2041 | ochoa | Protein bassoon (Zinc finger protein 231) | Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released (PubMed:12812759). After synthesis, participates in the formation of Golgi-derived membranous organelles termed Piccolo-Bassoon transport vesicles (PTVs) that are transported along axons to sites of nascent synaptic contacts (PubMed:19380881). At the presynaptic active zone, regulates the spatial organization of synaptic vesicle cluster, the protein complexes that execute membrane fusion and compensatory endocytosis (By similarity). Also functions in processes other than assembly such as the regulation of specific presynaptic protein ubiquitination by interacting with SIAH1 or the regulation of presynaptic autophagy by associating with ATG5 (By similarity). Also mediates synapse to nucleus communication leading to reconfiguration of gene expression by associating with the transcriptional corepressor CTBP1 and by subsequently reducing the size of its pool available for nuclear import (By similarity). Inhibits the activity of the proportion of DAO enzyme that localizes to the presynaptic active zone, which may modulate synaptic transmission (By similarity). {ECO:0000250|UniProtKB:O35078, ECO:0000250|UniProtKB:O88778, ECO:0000269|PubMed:12812759, ECO:0000269|PubMed:19380881}. |
| Q9UPN4 | CEP131 | S450 | ochoa | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9UPQ9 | TNRC6B | S421 | ochoa | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}. |
| Q9UPT8 | ZC3H4 | S1064 | ochoa | Zinc finger CCCH domain-containing protein 4 | RNA-binding protein that suppresses transcription of long non-coding RNAs (lncRNAs) (PubMed:33767452, PubMed:33913806). LncRNAs are defined as transcripts more than 200 nucleotides that are not translated into protein (PubMed:33767452, PubMed:33913806). Together with WDR82, part of a transcription termination checkpoint that promotes transcription termination of lncRNAs and their subsequent degradation by the exosome (PubMed:33767452, PubMed:33913806). The transcription termination checkpoint is activated by the inefficiently spliced first exon of lncRNAs (PubMed:33767452). {ECO:0000269|PubMed:33767452, ECO:0000269|PubMed:33913806}. |
| Q9UPU9 | SAMD4A | S649 | ochoa | Protein Smaug homolog 1 (Smaug 1) (hSmaug1) (Sterile alpha motif domain-containing protein 4A) (SAM domain-containing protein 4A) | Acts as a translational repressor of SRE-containing messengers. {ECO:0000269|PubMed:16221671}. |
| Q9UQ26 | RIMS2 | S1212 | ochoa | Regulating synaptic membrane exocytosis protein 2 (Rab-3-interacting molecule 2) (RIM 2) (Rab-3-interacting protein 3) | Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}. |
| Q9Y242 | TCF19 | S181 | ochoa | Transcription factor 19 (TCF-19) (Transcription factor SC1) | Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition (PubMed:1868030, PubMed:31141247). May bind to regulatory elements of genes, including the promoter of the transcription factor FOXO1 (PubMed:31141247). {ECO:0000269|PubMed:1868030, ECO:0000269|PubMed:31141247}. |
| Q9Y263 | PLAA | S484 | ochoa | Phospholipase A-2-activating protein (PLA2P) (PLAP) | Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (PubMed:27753622). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (By similarity). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell development (By similarity). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:18291623, PubMed:28007986). {ECO:0000250|UniProtKB:P27612, ECO:0000269|PubMed:18291623, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:28007986}. |
| Q9Y276 | BCS1L | S174 | ochoa | Mitochondrial chaperone BCS1 (h-BCS1) (EC 3.6.1.-) (BCS1-like protein) | Chaperone necessary for the incorporation of Rieske iron-sulfur protein UQCRFS1 into the mitochondrial respiratory chain complex III (PubMed:11528392, PubMed:9878253). Plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex (PubMed:18628306). {ECO:0000269|PubMed:11528392, ECO:0000269|PubMed:18628306, ECO:0000269|PubMed:9878253}. |
| Q9Y286 | SIGLEC7 | S404 | ochoa | Sialic acid-binding Ig-like lectin 7 (Siglec-7) (Adhesion inhibitory receptor molecule 1) (AIRM-1) (CDw328) (D-siglec) (QA79 membrane protein) (p75) (CD antigen CD328) | Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl globoside, disialyl lactotetraosylceramide and disialyl GalNAc lactotetraoslylceramide). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Mediates inhibition of natural killer cells cytotoxicity. May play a role in hemopoiesis. Inhibits differentiation of CD34+ cell precursors towards myelomonocytic cell lineage and proliferation of leukemic myeloid cells (in vitro). {ECO:0000269|PubMed:10611343}. |
| Q9Y2D8 | SSX2IP | S591 | ochoa | Afadin- and alpha-actinin-binding protein (ADIP) (Afadin DIL domain-interacting protein) (SSX2-interacting protein) | Belongs to an adhesion system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). May connect the nectin-afadin and E-cadherin-catenin system through alpha-actinin and may be involved in organization of the actin cytoskeleton at AJs through afadin and alpha-actinin (By similarity). Involved in cell movement: localizes at the leading edge of moving cells in response to PDGF and is required for the formation of the leading edge and the promotion of cell movement, possibly via activation of Rac signaling (By similarity). Acts as a centrosome maturation factor, probably by maintaining the integrity of the pericentriolar material and proper microtubule nucleation at mitotic spindle poles. The function seems to implicate at least in part WRAP73; the SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome (PubMed:23816619, PubMed:26545777). Involved in ciliogenesis (PubMed:24356449). It is required for targeted recruitment of the BBSome, CEP290, RAB8, and SSTR3 to the cilia (PubMed:24356449). {ECO:0000250|UniProtKB:Q8VC66, ECO:0000269|PubMed:23816619, ECO:0000269|PubMed:24356449, ECO:0000305|PubMed:26545777}. |
| Q9Y2G8 | DNAJC16 | S725 | ochoa | DnaJ homolog subfamily C member 16 (Endoplasmic reticulum DNA J domain-containing protein 8) (ER-resident protein ERdj8) (ERdj8) | Plays an important role in regulating the size of autophagosomes during the formation process. {ECO:0000269|PubMed:32492081}. |
| Q9Y2H9 | MAST1 | S139 | ochoa | Microtubule-associated serine/threonine-protein kinase 1 (EC 2.7.11.1) (Syntrophin-associated serine/threonine-protein kinase) | Microtubule-associated protein essential for correct brain development (PubMed:30449657). Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins (By similarity). {ECO:0000250|UniProtKB:Q9R1L5, ECO:0000269|PubMed:30449657}. |
| Q9Y2K9 | STXBP5L | S593 | ochoa | Syntaxin-binding protein 5-like (Lethal(2) giant larvae protein homolog 4) (Tomosyn-2) | Plays a role in vesicle trafficking and exocytosis inhibition. In pancreatic beta-cells, inhibits insulin secretion probably by interacting with and regulating STX1A and STX4, key t-SNARE proteins involved in the fusion of insulin granules to the plasma membrane. Also plays a role in neurotransmitter release by inhibiting basal acetylcholine release from axon terminals and by preventing synaptic fatigue upon repetitive stimulation (By similarity). Promotes as well axonal outgrowth (PubMed:25504045). {ECO:0000250|UniProtKB:Q5DQR4, ECO:0000269|PubMed:25504045}. |
| Q9Y2L6 | FRMD4B | S926 | ochoa | FERM domain-containing protein 4B (GRP1-binding protein GRSP1) | Member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling. May function as a scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex. Plays a redundant role with FRMD4A in epithelial polarization. {ECO:0000250|UniProtKB:Q920B0}. |
| Q9Y2W1 | THRAP3 | S377 | ochoa | Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) | Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| Q9Y3B9 | RRP15 | S220 | ochoa | RRP15-like protein (Ribosomal RNA-processing protein 15) | None |
| Q9Y3M8 | STARD13 | S430 | ochoa | StAR-related lipid transfer protein 13 (46H23.2) (Deleted in liver cancer 2 protein) (DLC-2) (Rho GTPase-activating protein) (START domain-containing protein 13) (StARD13) | GTPase-activating protein for RhoA, and perhaps for Cdc42. May be involved in regulation of cytoskeletal reorganization, cell proliferation and cell motility. Acts a tumor suppressor in hepatocellular carcinoma cells. {ECO:0000269|PubMed:14697242, ECO:0000269|PubMed:16217026}. |
| Q9Y3P9 | RABGAP1 | S56 | ochoa | Rab GTPase-activating protein 1 (GAP and centrosome-associated protein) (Rab6 GTPase-activating protein GAPCenA) | May act as a GTPase-activating protein of RAB6A. May play a role in microtubule nucleation by centrosome. May participate in a RAB6A-mediated pathway involved in the metaphase-anaphase transition. {ECO:0000269|PubMed:10202141, ECO:0000269|PubMed:16395330}. |
| Q9Y3S1 | WNK2 | S1889 | ochoa | Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Antigen NY-CO-43) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Serologically defined colon cancer antigen 43) | Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (PubMed:17667937, PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (PubMed:17667937, PubMed:18593598). {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}. |
| Q9Y426 | C2CD2 | S662 | ochoa | C2 domain-containing protein 2 (Transmembrane protein 24-like) | None |
| Q9Y490 | TLN1 | S2279 | ochoa | Talin-1 | High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane. With KANK1 co-organize the assembly of cortical microtubule stabilizing complexes (CMSCs) positioned to control microtubule-actin crosstalk at focal adhesions (FAs) rims. {ECO:0000250|UniProtKB:P26039}. |
| Q9Y4F1 | FARP1 | S473 | ochoa | FERM, ARHGEF and pleckstrin domain-containing protein 1 (Chondrocyte-derived ezrin-like protein) (FERM, RhoGEF and pleckstrin domain-containing protein 1) (Pleckstrin homology domain-containing family C member 2) (PH domain-containing family C member 2) | Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity). {ECO:0000250}. |
| Q9Y4F5 | CEP170B | S1267 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y4G6 | TLN2 | S646 | ochoa | Talin-2 | As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion. Recruits PIP5K1C to focal adhesion plaques and strongly activates its kinase activity (By similarity). {ECO:0000250}. |
| Q9Y5A9 | YTHDF2 | S196 | ochoa | YTH domain-containing family protein 2 (DF2) (CLL-associated antigen KW-14) (High-glucose-regulated protein 8) (Renal carcinoma antigen NY-REN-2) | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:25412658, PubMed:25412661, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31292544, PubMed:31388144, PubMed:31642031, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440). {ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658, ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30065315, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:30930054, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:31642031, ECO:0000269|PubMed:31815440, ECO:0000269|PubMed:32169943, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282). {ECO:0000269|PubMed:29447282}.; FUNCTION: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}. |
| Q9Y5K6 | CD2AP | S224 | ochoa | CD2-associated protein (Adapter protein CMS) (Cas ligand with multiple SH3 domains) | Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). {ECO:0000250|UniProtKB:F1LRS8, ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:22891260}. |
| Q9Y5W7 | SNX14 | S485 | ochoa | Sorting nexin-14 | Plays a role in maintaining normal neuronal excitability and synaptic transmission. May be involved in several stages of intracellular trafficking (By similarity). Required for autophagosome clearance, possibly by mediating the fusion of lysosomes with autophagosomes (Probable). Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes/lysosomes (PubMed:25848753). Does not bind phosphatidylinositol 3-phosphate (PtdIns(3P)) (PubMed:25148684, PubMed:25848753). {ECO:0000250|UniProtKB:Q8BHY8, ECO:0000269|PubMed:25148684, ECO:0000269|PubMed:25848753, ECO:0000305|PubMed:25848753}. |
| Q9Y5Z4 | HEBP2 | S37 | ochoa | Heme-binding protein 2 (Placental protein 23) (PP23) (Protein SOUL) | Can promote mitochondrial permeability transition and facilitate necrotic cell death under different types of stress conditions. {ECO:0000269|PubMed:17098234}. |
| Q9Y6D5 | ARFGEF2 | S1024 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (Brefeldin A-inhibited GEP 2) (ADP-ribosylation factor guanine nucleotide-exchange factor 2) | Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}. |
| Q9Y6G9 | DYNC1LI1 | S427 | ochoa | Cytoplasmic dynein 1 light intermediate chain 1 (LIC1) (Dynein light chain A) (DLC-A) (Dynein light intermediate chain 1, cytosolic) (DLIC-1) | Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. Probably involved in the microtubule-dependent transport of pericentrin. Is required for progress through the spindle assembly checkpoint. The phosphorylated form appears to be involved in the selective removal of MAD1L1 and MAD1L2 but not BUB1B from kinetochores. Forms a functional Rab11/RAB11FIP3/dynein complex onto endosomal membrane that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (PubMed:20026645). {ECO:0000269|PubMed:19229290, ECO:0000269|PubMed:20026645}. |
| Q9Y6M5 | SLC30A1 | S426 | ochoa | Proton-coupled zinc antiporter SLC30A1 (Solute carrier family 30 member 1) (Zinc transporter 1) | Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444). Forms a complex with TMC6/EVER1 and TMC8/EVER2 at the ER membrane of keratynocytes which facilitates zinc uptake into the ER (PubMed:18158319). Down-regulates the activity of transcription factors induced by zinc and cytokines (PubMed:18158319). {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:18158319, ECO:0000269|PubMed:31471319, ECO:0000269|PubMed:32441444}. |
| Q9Y6N7 | ROBO1 | S1157 | ochoa | Roundabout homolog 1 (Deleted in U twenty twenty) (H-Robo-1) | Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). May be required for lung development (By similarity). {ECO:0000250|UniProtKB:O89026, ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:24560577, ECO:0000269|PubMed:26529257, ECO:0000305}. |
| Q9Y2B0 | CNPY2 | S55 | Sugiyama | Protein canopy homolog 2 (MIR-interacting saposin-like protein) (Putative secreted protein Zsig9) (Transmembrane protein 4) | Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation. |
| P13667 | PDIA4 | S379 | Sugiyama | Protein disulfide-isomerase A4 (EC 5.3.4.1) (Endoplasmic reticulum resident protein 70) (ER protein 70) (ERp70) (Endoplasmic reticulum resident protein 72) (ER protein 72) (ERp-72) (ERp72) | None |
| P20618 | PSMB1 | S157 | Sugiyama | Proteasome subunit beta type-1 (Macropain subunit C5) (Multicatalytic endopeptidase complex subunit C5) (Proteasome component C5) (Proteasome gamma chain) (Proteasome subunit beta-6) (beta-6) | Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P36871 | PGM1 | S483 | Sugiyama | Phosphoglucomutase-1 (PGM 1) (EC 5.4.2.2) (Glucose phosphomutase 1) | Catalyzes the reversible isomerization of alpha-D-glucose 1-phosphate to alpha-D-glucose 6-phosphate (PubMed:15378030, PubMed:25288802). The mechanism proceeds via the intermediate compound alpha-D-glucose 1,6-bisphosphate (Probable) (PubMed:25288802). This enzyme participates in both the breakdown and synthesis of glucose (PubMed:17924679, PubMed:25288802). {ECO:0000269|PubMed:15378030, ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:25288802, ECO:0000305|PubMed:15378030}. |
| P57721 | PCBP3 | S59 | Sugiyama | Poly(rC)-binding protein 3 (Alpha-CP3) (PCBP3-overlapping transcript) (PCBP3-overlapping transcript 1) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. {ECO:0000250}. |
| Q15366 | PCBP2 | S27 | Sugiyama | Poly(rC)-binding protein 2 (Alpha-CP2) (Heterogeneous nuclear ribonucleoprotein E2) (hnRNP E2) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:12414943, PubMed:7607214). Major cellular poly(rC)-binding protein (PubMed:12414943). Also binds poly(rU) (PubMed:12414943). Acts as a negative regulator of antiviral signaling (PubMed:19881509, PubMed:35322803). Negatively regulates cellular antiviral responses mediated by MAVS signaling (PubMed:19881509). It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation (PubMed:19881509). Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid-like droplets in which CGAS is activated (PubMed:35322803). Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:Q61990, ECO:0000269|PubMed:12414943, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:35322803, ECO:0000269|PubMed:7607214}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12414943, PubMed:24371074). Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD (PubMed:12414943). {ECO:0000269|PubMed:12414943, ECO:0000269|PubMed:24371074}. |
| P07602 | PSAP | S29 | Sugiyama | Prosaposin (Proactivator polypeptide) [Cleaved into: Saposin-A (Protein A); Saposin-B-Val; Saposin-B (Cerebroside sulfate activator) (CSAct) (Dispersin) (Sphingolipid activator protein 1) (SAP-1) (Sulfatide/GM1 activator); Saposin-C (A1 activator) (Co-beta-glucosidase) (Glucosylceramidase activator) (Sphingolipid activator protein 2) (SAP-2); Saposin-D (Component C) (Protein C)] | Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.; FUNCTION: Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.; FUNCTION: Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).; FUNCTION: [Prosaposin]: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling. {ECO:0000250|UniProtKB:Q61207, ECO:0000269|PubMed:10383054}.; FUNCTION: Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases. |
| P35606 | COPB2 | S350 | Sugiyama | Coatomer subunit beta' (Beta'-coat protein) (Beta'-COP) (p102) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. {ECO:0000269|PubMed:34450031}.; FUNCTION: This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner (By similarity). {ECO:0000250}. |
| O15357 | INPPL1 | S43 | Sugiyama | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (EC 3.1.3.86) (Inositol polyphosphate phosphatase-like protein 1) (INPPL-1) (Protein 51C) (SH2 domain-containing inositol 5'-phosphatase 2) (SH2 domain-containing inositol phosphatase 2) (SHIP-2) | Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:16824732). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:9660833). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (By similarity). Part of a signaling pathway that regulates actin cytoskeleton remodeling (PubMed:11739414, PubMed:12676785). Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation (PubMed:15668240). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading (PubMed:12235291). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (PubMed:15735664). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (PubMed:17135240). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (PubMed:12690104). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:11016922). Involved in EGF signaling pathway (PubMed:11349134). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (PubMed:11349134). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (PubMed:11349134). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (PubMed:23273569). {ECO:0000250|UniProtKB:F1PNY0, ECO:0000250|UniProtKB:Q6P549, ECO:0000250|UniProtKB:Q9WVR3, ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12676785, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15668240, ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:17135240, ECO:0000269|PubMed:21624956, ECO:0000269|PubMed:23273569, ECO:0000269|PubMed:9660833}. |
| P33993 | MCM7 | S409 | Sugiyama | DNA replication licensing factor MCM7 (EC 3.6.4.12) (CDC47 homolog) (P1.1-MCM3) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for S-phase checkpoint activation upon UV-induced damage. {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:25661590, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| P28340 | POLD1 | S1064 | Sugiyama | DNA polymerase delta catalytic subunit (EC 2.7.7.7) (3'-5' exodeoxyribonuclease) (EC 3.1.11.-) (DNA polymerase subunit delta p125) | As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200, PubMed:31449058). Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24022480, PubMed:24035200). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025). {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24191025, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:31449058}. |
| P61163 | ACTR1A | S247 | Sugiyama | Alpha-centractin (Centractin) (ARP1) (Actin-RPV) (Centrosome-associated actin homolog) | Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules. {ECO:0000250|UniProtKB:F2Z5G5}. |
| P41221 | WNT5A | S132 | Sugiyama | Protein Wnt-5a | Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor (PubMed:15735754). Mediates motility of melanoma cells (PubMed:17426020). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes (By similarity). {ECO:0000250|UniProtKB:P22725, ECO:0000250|UniProtKB:Q27Q52, ECO:0000269|PubMed:15735754, ECO:0000269|PubMed:17426020}. |
| Q9H1J7 | WNT5B | S111 | Sugiyama | Protein Wnt-5b | Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity). {ECO:0000250}. |
| P41091 | EIF2S3 | S410 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 3 (EC 3.6.5.3) (Eukaryotic translation initiation factor 2 subunit gamma X) (eIF2-gamma X) (eIF2gX) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:31836389). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC) (By similarity). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex (By similarity). In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). {ECO:0000250|UniProtKB:P05198, ECO:0000269|PubMed:31836389}. |
| Q2VIR3 | EIF2S3B | S410 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 3B (EC 3.6.5.3) (Eukaryotic translation initiation factor 2 subunit gamma A) (eIF-2-gamma A) (eIF-2gA) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). {ECO:0000250|UniProtKB:P05198}. |
| P23396 | RPS3 | S83 | Sugiyama | Small ribosomal subunit protein uS3 (40S ribosomal protein S3) (EC 4.2.99.18) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:8706699). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:8706699). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (PubMed:15707971). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Has also been shown to bind with similar affinity to intact and damaged DNA (PubMed:18610840). Stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571). Enhances the uracil excision activity of UNG1 (PubMed:18973764). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (PubMed:18045535). Represses its own translation by binding to its cognate mRNA (PubMed:20217897). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408). {ECO:0000269|PubMed:14706345, ECO:0000269|PubMed:14988002, ECO:0000269|PubMed:15518571, ECO:0000269|PubMed:15707971, ECO:0000269|PubMed:17049931, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:18610840, ECO:0000269|PubMed:18973764, ECO:0000269|PubMed:19656744, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:22510408, ECO:0000269|PubMed:23131551, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:23911537, ECO:0000269|PubMed:7775413, ECO:0000269|PubMed:8706699}. |
| P35408 | PTGER4 | S354 | ELM | Prostaglandin E2 receptor EP4 subtype (PGE receptor EP4 subtype) (PGE2 receptor EP4 subtype) (Prostanoid EP4 receptor) | Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function. |
| P68104 | EEF1A1 | S53 | SIGNOR | Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}. |
| Q05639 | EEF1A2 | S53 | SIGNOR | Elongation factor 1-alpha 2 (EF-1-alpha-2) (EC 3.6.5.-) (Eukaryotic elongation factor 1 A-2) (eEF1A-2) (Statin-S1) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (By similarity). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (By similarity). {ECO:0000250|UniProtKB:P68104, ECO:0000250|UniProtKB:Q71V39}. |
| P14616 | INSRR | S989 | Sugiyama | Insulin receptor-related protein (IRR) (EC 2.7.10.1) (IR-related receptor) [Cleaved into: Insulin receptor-related protein alpha chain; Insulin receptor-related protein beta chain] | Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB. {ECO:0000269|PubMed:21641549}. |
| P41091 | EIF2S3 | S282 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 3 (EC 3.6.5.3) (Eukaryotic translation initiation factor 2 subunit gamma X) (eIF2-gamma X) (eIF2gX) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:31836389). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC) (By similarity). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex (By similarity). In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). {ECO:0000250|UniProtKB:P05198, ECO:0000269|PubMed:31836389}. |
| Q2VIR3 | EIF2S3B | S282 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 3B (EC 3.6.5.3) (Eukaryotic translation initiation factor 2 subunit gamma A) (eIF-2-gamma A) (eIF-2gA) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). {ECO:0000250|UniProtKB:P05198}. |
| P61964 | WDR5 | S184 | Sugiyama | WD repeat-containing protein 5 (BMP2-induced 3-kb gene protein) | Contributes to histone modification (PubMed:16600877, PubMed:16829960, PubMed:19103755, PubMed:19131338, PubMed:19556245, PubMed:20018852). May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4' (PubMed:16829960). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:18840606). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:19103755, PubMed:20018852). May regulate osteoblasts differentiation (By similarity). In association with RBBP5 and ASH2L, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000250|UniProtKB:P61965, ECO:0000269|PubMed:16600877, ECO:0000269|PubMed:16829960, ECO:0000269|PubMed:18840606, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}. |
| Q12805 | EFEMP1 | S196 | Sugiyama | EGF-containing fibulin-like extracellular matrix protein 1 (Extracellular protein S1-5) (Fibrillin-like protein) (Fibulin-3) (FIBL-3) | Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulator of chondrocyte differentiation. In the olfactory epithelium, it may regulate glial cell migration, differentiation and the ability of glial cells to support neuronal neurite outgrowth. {ECO:0000269|PubMed:19804359, ECO:0000269|PubMed:19887559, ECO:0000269|PubMed:20005202}. |
| Q5T6F2 | UBAP2 | S856 | Sugiyama | Ubiquitin-associated protein 2 (UBAP-2) (RNA polymerase II degradation factor UBAP2) | Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). May promote the degradation of ANXA2 (PubMed:27121050). {ECO:0000269|PubMed:27121050, ECO:0000269|PubMed:35633597}. |
| Q9NZV7 | ZIM2 | S158 | Sugiyama | Zinc finger imprinted 2 (Zinc finger protein 656) | May be involved in transcriptional regulation. |
| Q9BRS2 | RIOK1 | S503 | Sugiyama | Serine/threonine-protein kinase RIO1 (EC 2.7.11.1) (EC 3.6.1.-) (RIO kinase 1) | Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor (PubMed:22072790). The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit (By similarity). Despite the protein kinase domain is proposed to act predominantly as an ATPase (By similarity). The catalytic activity regulates its dynamic association with the 40S subunit (By similarity). In addition to its role in ribosomal biogenesis acts as an adapter protein by recruiting NCL/nucleolin the to PRMT5 complex for its symmetrical methylation (PubMed:21081503). {ECO:0000250|UniProtKB:G0S3J5, ECO:0000250|UniProtKB:Q12196, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:22072790}. |
| Q99626 | CDX2 | S295 | SIGNOR | Homeobox protein CDX-2 (CDX-3) (Caudal-type homeobox protein 2) | Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium (By similarity). Binds to the promoter of the intestinal sucrase-isomaltase SI and activates SI transcription (By similarity). Binds to the DNA sequence 5'-ATAAAAACTTAT-3' in the promoter region of VDR and activates VDR transcription (By similarity). Binds to and activates transcription of LPH (By similarity). Activates transcription of CLDN2 and intestinal mucin MUC2 (By similarity). Binds to the 5'-AATTTTTTACAACACCT-3' DNA sequence in the promoter region of CA1 and activates CA1 transcription (By similarity). Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000250|UniProtKB:P43241, ECO:0000250|UniProtKB:Q04649, ECO:0000269|PubMed:28473536}. |
| P14866 | HNRNPL | S471 | Sugiyama | Heterogeneous nuclear ribonucleoprotein L (hnRNP L) | Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:22570490, PubMed:24164894, PubMed:25623890, PubMed:26051023). Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts (PubMed:2687284). Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter (PubMed:11809897). As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). Regulates alternative splicing of a core group of genes involved in neuronal differentiation, likely by mediating H3K36me3-coupled transcription elongation and co-transcriptional RNA processing via interaction with CHD8. {ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:22570490, ECO:0000269|PubMed:25623890, ECO:0000269|PubMed:26051023, ECO:0000269|PubMed:2687284, ECO:0000269|PubMed:33174841, ECO:0000269|PubMed:36537238}. |
| Q5T4S7 | UBR4 | S2932 | EPSD|PSP | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| P42681 | TXK | S305 | Sugiyama | Tyrosine-protein kinase TXK (EC 2.7.10.2) (Protein-tyrosine kinase 4) (Resting lymphocyte kinase) | Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation leads to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Also contributes to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with PARP1 and EEF1A1 (PubMed:11859127, PubMed:17177976). Within the complex, phosphorylates both PARP1 and EEF1A1 (PubMed:17177976). Also phosphorylates key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor. {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:11564877, ECO:0000269|PubMed:11859127, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:9813138}. |
| P10636 | MAPT | S641 | SIGNOR|EPSD | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| O60563 | CCNT1 | S369 | Sugiyama | Cyclin-T1 (CycT1) (Cyclin-T) | Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:35393539}.; FUNCTION: (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. {ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10329126}. |
| P51812 | RPS6KA3 | S432 | Sugiyama | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
| Q9UK32 | RPS6KA6 | S436 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| P53671 | LIMK2 | S36 | Sugiyama | LIM domain kinase 2 (LIMK-2) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics (PubMed:10436159, PubMed:11018042). Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11018042). Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP (PubMed:22328514). Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro (PubMed:8537403). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:8537403}. |
| P11388 | TOP2A | S390 | Sugiyama | DNA topoisomerase 2-alpha (EC 5.6.2.2) (DNA topoisomerase II, alpha isozyme) | Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity). {ECO:0000250|UniProtKB:Q01320, ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22323612}. |
| P52788 | SMS | S57 | Sugiyama | Spermine synthase (SPMSY) (EC 2.5.1.22) (Spermidine aminopropyltransferase) | Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM). {ECO:0000269|PubMed:18367445, ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. |
| Q5HYK3 | COQ5 | S165 | Sugiyama | 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (EC 2.1.1.201) (Ubiquinone biosynthesis methyltransferase COQ5) | Methyltransferase required for the conversion of 2-decaprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-decaprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2). {ECO:0000255|HAMAP-Rule:MF_03191, ECO:0000269|PubMed:38425362}. |
| P39019 | RPS19 | S96 | Sugiyama | Small ribosomal subunit protein eS19 (40S ribosomal protein S19) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for pre-rRNA processing and maturation of 40S ribosomal subunits (PubMed:16990592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:16990592, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| Q06187 | BTK | S557 | Sugiyama | Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) | Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}. |
| Q06210 | GFPT1 | S242 | SIGNOR | Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 (EC 2.6.1.16) (D-fructose-6-phosphate amidotransferase 1) (Glutamine:fructose-6-phosphate amidotransferase 1) (GFAT 1) (GFAT1) (Hexosephosphate aminotransferase 1) | Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (PubMed:26887390). {ECO:0000250|UniProtKB:P47856, ECO:0000269|PubMed:26887390}. |
| Q16816 | PHKG1 | S58 | Sugiyama | Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHK-gamma-M) (EC 2.7.11.19) (Phosphorylase kinase subunit gamma-1) (Serine/threonine-protein kinase PHKG1) (EC 2.7.11.1, EC 2.7.11.26) | Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity). {ECO:0000250}. |
| P49327 | FASN | S324 | Sugiyama | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| Q06124 | PTPN11 | S28 | Sugiyama | Tyrosine-protein phosphatase non-receptor type 11 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1D) (PTP-1D) (Protein-tyrosine phosphatase 2C) (PTP-2C) (SH-PTP2) (SHP-2) (Shp2) (SH-PTP3) | Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:14739280, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity). Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L (PubMed:19275884). {ECO:0000250|UniProtKB:P35235, ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:14739280, ECO:0000269|PubMed:18559669, ECO:0000269|PubMed:18829466, ECO:0000269|PubMed:19275884, ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:28074573}. |
| P42025 | ACTR1B | S247 | Sugiyama | Beta-centractin (Actin-related protein 1B) (ARP1B) | Component of a multi-subunit complex involved in microtubule based vesicle motility. It is associated with the centrosome. |
| Q8N5S9 | CAMKK1 | S57 | Sugiyama | Calcium/calmodulin-dependent protein kinase kinase 1 (CaM-KK 1) (CaM-kinase kinase 1) (CaMKK 1) (EC 2.7.11.17) (CaM-kinase IV kinase) (Calcium/calmodulin-dependent protein kinase kinase alpha) (CaM-KK alpha) (CaM-kinase kinase alpha) (CaMKK alpha) | Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. {ECO:0000269|PubMed:12935886}. |
| Q8NG66 | NEK11 | S39 | Sugiyama | Serine/threonine-protein kinase Nek11 (EC 2.7.11.1) (Never in mitosis A-related kinase 11) (NimA-related protein kinase 11) | Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation. {ECO:0000269|PubMed:12154088, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422}. |
| Q8TD08 | MAPK15 | S349 | Sugiyama | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| Q92630 | DYRK2 | S474 | Sugiyama | Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC 2.7.12.1) | Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}. |
| Q96J92 | WNK4 | S316 | Sugiyama | Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4) | Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:16832045). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16832045, PubMed:22989884). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (By similarity). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (By similarity). Also inhibits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (By similarity). May also phosphorylate NEDD4L (PubMed:20525693). {ECO:0000250|UniProtKB:Q80UE6, ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:22989884}. |
| Q96RR4 | CAMKK2 | S503 | Sugiyama | Calcium/calmodulin-dependent protein kinase kinase 2 (CaM-KK 2) (CaM-kinase kinase 2) (CaMKK 2) (EC 2.7.11.17) (Calcium/calmodulin-dependent protein kinase kinase beta) (CaM-KK beta) (CaM-kinase kinase beta) (CaMKK beta) | Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496, ECO:0000269|PubMed:9662074}. |
| Q9H093 | NUAK2 | S325 | Sugiyama | NUAK family SNF1-like kinase 2 (EC 2.7.11.1) (Omphalocele kinase 2) (SNF1/AMP kinase-related kinase) (SNARK) | Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958). {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:32845958}. |
| Q9H2X6 | HIPK2 | S955 | Sugiyama | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| O95263 | PDE8B | S428 | Sugiyama | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (HsPDE8B) (EC 3.1.4.53) (Cell proliferation-inducing gene 22 protein) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland. |
| Q9NZB2 | FAM120A | S30 | Sugiyama | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q14524 | SCN5A | S539 | PSP | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q9BYP7 | WNK3 | S289 | Sugiyama | Serine/threonine-protein kinase WNK3 (EC 2.7.11.1) (Protein kinase lysine-deficient 3) (Protein kinase with no lysine 3) | Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922). WNK3 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:22989884). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16275911, PubMed:16275913). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (PubMed:17975670). May also phosphorylate NEDD4L (PubMed:20525693). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (PubMed:16357011, PubMed:17673510). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17673510, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:36318922}. |
| Q9H4A3 | WNK1 | S363 | Sugiyama | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9Y3S1 | WNK2 | S337 | Sugiyama | Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Antigen NY-CO-43) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Serologically defined colon cancer antigen 43) | Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (PubMed:17667937, PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (PubMed:17667937, PubMed:18593598). {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}. |
| B5ME19 | EIF3CL | S866 | ochoa | Eukaryotic translation initiation factor 3 subunit C-like protein | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. {ECO:0000250|UniProtKB:Q99613}. |
| O00232 | PSMD12 | S332 | ochoa | 26S proteasome non-ATPase regulatory subunit 12 (26S proteasome regulatory subunit RPN5) (26S proteasome regulatory subunit p55) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}. |
| O00267 | SUPT5H | S782 | ochoa|psp | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00311 | CDC7 | S27 | ochoa | Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) | Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}. |
| O00571 | DDX3X | S410 | ochoa | ATP-dependent RNA helicase DDX3X (EC 3.6.4.13) (CAP-Rf) (DEAD box protein 3, X-chromosomal) (DEAD box, X isoform) (DBX) (Helicase-like protein 2) (HLP2) | Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:17667941, PubMed:18628297, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150). This function depends on helicase activity (PubMed:20837705, PubMed:22872150). Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705). Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150). Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517). Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705). May activate TP53 translation (PubMed:28842590). Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517). Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941). Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:20127681, PubMed:21170385, PubMed:31575075). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385, PubMed:33674311). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:19913487, PubMed:21170385, PubMed:27980081). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265). Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167). Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167). Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973). May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960). Involved in both stress and inflammatory responses (By similarity). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity). Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110). Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110). Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110). ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110). May be involved in mitotic chromosome segregation (PubMed:21730191). {ECO:0000250|UniProtKB:Q62167, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17095540, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:27736973, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29222110, ECO:0000269|PubMed:30256975, ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:31575075, ECO:0000269|PubMed:33674311, ECO:0000305}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385). {ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960). {ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication. {ECO:0000269|PubMed:27105836}. |
| O14497 | ARID1A | S1516 | ochoa | AT-rich interactive domain-containing protein 1A (ARID domain-containing protein 1A) (B120) (BRG1-associated factor 250) (BAF250) (BRG1-associated factor 250a) (BAF250A) (Osa homolog 1) (hOSA1) (SWI-like protein) (SWI/SNF complex protein p270) (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1) (hELD) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:A2BH40, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| O14545 | TRAFD1 | Y433 | ochoa | TRAF-type zinc finger domain-containing protein 1 (Protein FLN29) | Negative feedback regulator that controls excessive innate immune responses. Regulates both Toll-like receptor 4 (TLR4) and DDX58/RIG1-like helicases (RLH) pathways. May inhibit the LTR pathway by direct interaction with TRAF6 and attenuation of NF-kappa-B activation. May negatively regulate the RLH pathway downstream from MAVS and upstream of NF-kappa-B and IRF3 (By similarity). {ECO:0000250, ECO:0000269|PubMed:16221674}. |
| O15014 | ZNF609 | S810 | ochoa | Zinc finger protein 609 | Transcription factor, which activates RAG1, and possibly RAG2, transcription. Through the regulation of RAG1/2 expression, may regulate thymocyte maturation. Along with NIPBL and the multiprotein complex Integrator, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others. {ECO:0000250|UniProtKB:Q8BZ47}.; FUNCTION: [Isoform 2]: Involved in the regulation of myoblast proliferation during myogenesis. {ECO:0000269|PubMed:28344082}. |
| O15061 | SYNM | S628 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15111 | CHUK | S176 | psp | Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK-1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}. |
| O15439 | ABCC4 | S629 | ochoa | ATP-binding cassette sub-family C member 4 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (MRP/cMOAT-related ABC transporter) (Multi-specific organic anion transporter B) (MOAT-B) (Multidrug resistance-associated protein 4) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685). {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:12523936, ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:16282361, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:18300232, ECO:0000269|PubMed:26721430}. |
| O15446 | POLR1G | S459 | ochoa | DNA-directed RNA polymerase I subunit RPA34 (A34.5) (Antisense to ERCC-1 protein) (ASE-1) (CD3-epsilon-associated protein) (CD3E-associated protein) (DNA-directed RNA polymerase I subunit G) (RNA polymerase I-associated factor PAF49) | Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Involved in UBTF-activated transcription, presumably at a step following PIC formation. {ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492}.; FUNCTION: [Isoform 2]: Has been described as a component of preformed T-cell receptor (TCR) complex. {ECO:0000269|PubMed:10373416}. |
| O15523 | DDX3Y | S408 | ochoa | ATP-dependent RNA helicase DDX3Y (EC 3.6.4.13) (DEAD box protein 3, Y-chromosomal) | Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway (By similarity). {ECO:0000250|UniProtKB:Q62095}. |
| O43314 | PPIP5K2 | S1072 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}. |
| O43448 | KCNAB3 | S184 | ochoa | Voltage-gated potassium channel subunit beta-3 (EC 1.1.1.-) (K(+) channel subunit beta-3) (Kv-beta-3) | Regulatory subunit of the voltage-gated potassium (Kv) channels composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunit (PubMed:9857044). The beta-3/KCNAB3 subunit may mediate closure of potassium channels (By similarity). Increases inactivation of Kv1.5/KCNA5 alpha subunit-containing channels (PubMed:9857044). May display nicotinamide adenine dinucleotide phosphate (NADPH)-dependent aldoketoreductase activity (By similarity). The binding of oxidized and reduced NADP(H) cofactors may be required for the regulation of potassium channel activity (By similarity). {ECO:0000250|UniProtKB:P62483, ECO:0000250|UniProtKB:P63144, ECO:0000269|PubMed:9857044}. |
| O43707 | ACTN4 | S507 | ochoa | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| O60271 | SPAG9 | S229 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60292 | SIPA1L3 | S204 | ochoa | Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}. |
| O60361 | NME2P1 | S105 | ochoa | Putative nucleoside diphosphate kinase (NDK) (NDP kinase) (EC 2.7.4.6) | Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). {ECO:0000250}. |
| O60658 | PDE8A | S359 | psp | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC 3.1.4.53) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299). {ECO:0000269|PubMed:18983167, ECO:0000269|PubMed:23509299}. |
| O60664 | PLIN3 | S179 | ochoa | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| O75038 | PLCH2 | S579 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-2) (Phosphoinositide phospholipase C-like 4) (PLC-L4) (Phospholipase C-like protein 4) (Phospholipase C-eta-2) (PLC-eta2) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes (PubMed:18361507). This phospholipase activity is very sensitive to calcium. May be important for formation and maintenance of the neuronal network in the postnatal brain (By similarity). {ECO:0000250|UniProtKB:A2AP18, ECO:0000269|PubMed:18361507}. |
| O75069 | TMCC2 | S78 | ochoa | Transmembrane and coiled-coil domains protein 2 (Cerebral protein 11) | May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE. {ECO:0000269|PubMed:21593558}. |
| O75083 | WDR1 | S230 | ochoa | WD repeat-containing protein 1 (Actin-interacting protein 1) (AIP1) (NORI-1) | Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (PubMed:15629458, PubMed:27557945, PubMed:29751004). Enhances cofilin-mediated actin severing (By similarity). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (PubMed:18494608). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance (By similarity). Involved in megakaryocyte maturation and platelet shedding. Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (By similarity). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (PubMed:25792565). {ECO:0000250|UniProtKB:O88342, ECO:0000250|UniProtKB:Q9W7F2, ECO:0000269|PubMed:15629458, ECO:0000269|PubMed:18494608, ECO:0000269|PubMed:25792565, ECO:0000269|PubMed:27557945, ECO:0000269|PubMed:29751004}. |
| O75665 | OFD1 | S986 | ochoa | Centriole and centriolar satellite protein OFD1 (Oral-facial-digital syndrome 1 protein) (Protein 71-7A) | Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250|UniProtKB:Q80Z25, ECO:0000269|PubMed:33934390}. |
| O75791 | GRAP2 | S236 | ochoa | GRB2-related adapter protein 2 (Adapter protein GRID) (GRB-2-like protein) (GRB2L) (GRBLG) (GRBX) (Grf40 adapter protein) (Grf-40) (Growth factor receptor-binding protein) (Hematopoietic cell-associated adapter protein GrpL) (P38) (Protein GADS) (SH3-SH2-SH3 adapter Mona) | Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc. |
| O94804 | STK10 | S514 | ochoa | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
| O94967 | WDR47 | S581 | ochoa | WD repeat-containing protein 47 (Neuronal enriched MAP-interacting protein) (Nemitin) | None |
| O95336 | PGLS | S49 | ochoa | 6-phosphogluconolactonase (6PGL) (EC 3.1.1.31) | Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate. {ECO:0000269|PubMed:10518023}. |
| O95425 | SVIL | S1000 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95671 | ASMTL | S246 | ochoa | Probable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein [Includes: dTTP/UTP pyrophosphatase (dTTPase/UTPase) (EC 3.6.1.9) (Nucleoside triphosphate pyrophosphatase) (Nucleotide pyrophosphatase) (Nucleotide PPase); N-acetylserotonin O-methyltransferase-like protein (ASMTL) (EC 2.1.1.-)] | Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP. Can also hydrolyze CTP and the modified nucleotides pseudo-UTP, 5-methyl-UTP (m(5)UTP) and 5-methyl-CTP (m(5)CTP). Has weak activity with dCTP, 8-oxo-GTP and N(4)-methyl-dCTP (PubMed:24210219). May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids (PubMed:24210219). In addition, the presence of the putative catalytic domain of S-adenosyl-L-methionine binding in the C-terminal region argues for a methyltransferase activity (Probable). {ECO:0000269|PubMed:24210219, ECO:0000305}. |
| O95671 | ASMTL | S255 | ochoa | Probable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein [Includes: dTTP/UTP pyrophosphatase (dTTPase/UTPase) (EC 3.6.1.9) (Nucleoside triphosphate pyrophosphatase) (Nucleotide pyrophosphatase) (Nucleotide PPase); N-acetylserotonin O-methyltransferase-like protein (ASMTL) (EC 2.1.1.-)] | Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP. Can also hydrolyze CTP and the modified nucleotides pseudo-UTP, 5-methyl-UTP (m(5)UTP) and 5-methyl-CTP (m(5)CTP). Has weak activity with dCTP, 8-oxo-GTP and N(4)-methyl-dCTP (PubMed:24210219). May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids (PubMed:24210219). In addition, the presence of the putative catalytic domain of S-adenosyl-L-methionine binding in the C-terminal region argues for a methyltransferase activity (Probable). {ECO:0000269|PubMed:24210219, ECO:0000305}. |
| O95758 | PTBP3 | S161 | ochoa | Polypyrimidine tract-binding protein 3 (Regulator of differentiation 1) (Rod1) | RNA-binding protein that mediates pre-mRNA alternative splicing regulation. Plays a role in the regulation of cell proliferation, differentiation and migration. Positive regulator of EPO-dependent erythropoiesis. Participates in cell differentiation regulation by repressing tissue-specific exons. Promotes FAS exon 6 skipping. Binds RNA, preferentially to both poly(G) and poly(U). {ECO:0000269|PubMed:10207106, ECO:0000269|PubMed:18335065, ECO:0000269|PubMed:19441079, ECO:0000269|PubMed:20937273}. |
| P04049 | RAF1 | S499 | ochoa|psp | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. |
| P06400 | RB1 | S866 | ochoa | Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110) | Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; FUNCTION: (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}. |
| P06748 | NPM1 | S260 | ochoa | Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) | Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}. |
| P07359 | GP1BA | S601 | ochoa|psp | Platelet glycoprotein Ib alpha chain (GP-Ib alpha) (GPIb-alpha) (GPIbA) (Glycoprotein Ibalpha) (Antigen CD42b-alpha) (CD antigen CD42b) [Cleaved into: Glycocalicin] | GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. |
| P10809 | HSPD1 | S488 | ochoa | 60 kDa heat shock protein, mitochondrial (EC 5.6.1.7) (60 kDa chaperonin) (Chaperonin 60) (CPN60) (Heat shock protein 60) (HSP-60) (Hsp60) (Heat shock protein family D member 1) (HuCHA60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) | Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}. |
| P11137 | MAP2 | S1742 | ochoa | Microtubule-associated protein 2 (MAP-2) | The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules. |
| P12268 | IMPDH2 | S416 | ochoa | Inosine-5'-monophosphate dehydrogenase 2 (IMP dehydrogenase 2) (IMPD 2) (IMPDH 2) (EC 1.1.1.205) (Inosine-5'-monophosphate dehydrogenase type II) (IMP dehydrogenase II) (IMPDH-II) | Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (PubMed:7763314, PubMed:7903306). Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism (PubMed:14766016). It may also have a role in the development of malignancy and the growth progression of some tumors. {ECO:0000269|PubMed:14766016, ECO:0000269|PubMed:7763314, ECO:0000269|PubMed:7903306}. |
| P12956 | XRCC6 | S520 | ochoa | X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Negatively regulates apoptosis by interacting with BAX and sequestering it from the mitochondria (PubMed:15023334). Might have deubiquitination activity, acting on BAX (PubMed:18362350). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:18362350, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. |
| P13196 | ALAS1 | S82 | ochoa | 5-aminolevulinate synthase, non-specific, mitochondrial (ALAS-H) (EC 2.3.1.37) (5-aminolevulinic acid synthase 1) (Delta-ALA synthase 1) (Delta-aminolevulinate synthase 1) | Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products. {ECO:0000269|PubMed:16234850, ECO:0000269|PubMed:17975826}. |
| P15311 | EZR | Y146 | psp | Ezrin (Cytovillin) (Villin-2) (p81) | Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}. |
| P15498 | VAV1 | S215 | ochoa | Proto-oncogene vav | Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. |
| P15531 | NME1 | S120 | ochoa|psp | Nucleoside diphosphate kinase A (NDK A) (NDP kinase A) (EC 2.7.4.6) (Granzyme A-activated DNase) (GAAD) (Metastasis inhibition factor nm23) (NM23-H1) (Tumor metastatic process-associated protein) | Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair. {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:8810265}. |
| P15880 | RPS2 | S190 | ochoa | Small ribosomal subunit protein uS5 (40S ribosomal protein S2) (40S ribosomal protein S4) (Protein LLRep3) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:23636399). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:23636399). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:23636399). Plays a role in the assembly and function of the 40S ribosomal subunit (By similarity). Mutations in this protein affects the control of translational fidelity (By similarity). Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly (By similarity). {ECO:0000250|UniProtKB:P25443, ECO:0000269|PubMed:23636399}. |
| P15924 | DSP | S2551 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P16615 | ATP2A2 | S555 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) | This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:12542527, PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}.; FUNCTION: [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. {ECO:0000250|UniProtKB:O55143}. |
| P18031 | PTPN1 | S378 | ochoa|psp | Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) | Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}. |
| P18206 | VCL | S345 | ochoa | Vinculin (Metavinculin) (MV) | Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}. |
| P18887 | XRCC1 | S408 | ochoa|psp | DNA repair protein XRCC1 (X-ray repair cross-complementing protein 1) | Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes (PubMed:11163244, PubMed:28002403). Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity (PubMed:28002403, PubMed:34102106, PubMed:34811483). Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity (PubMed:14500814, PubMed:34102106, PubMed:34811483). {ECO:0000269|PubMed:11163244, ECO:0000269|PubMed:14500814, ECO:0000269|PubMed:28002403, ECO:0000269|PubMed:34102106, ECO:0000269|PubMed:34811483}. |
| P20585 | MSH3 | S33 | ochoa | DNA mismatch repair protein Msh3 (hMSH3) (Divergent upstream protein) (DUP) (Mismatch repair protein 1) (MRP1) | Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. |
| P22392 | NME2 | S120 | ochoa | Nucleoside diphosphate kinase B (NDK B) (NDP kinase B) (EC 2.7.4.6) (C-myc purine-binding transcription factor PUF) (Histidine protein kinase NDKB) (EC 2.7.13.3) (nm23-H2) | Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:19435876, PubMed:8392752). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858). {ECO:0000250|UniProtKB:P36010, ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:19435876, ECO:0000269|PubMed:20946858, ECO:0000269|PubMed:25679041, ECO:0000269|PubMed:8392752}. |
| P23458 | JAK1 | S963 | ochoa | Tyrosine-protein kinase JAK1 (EC 2.7.10.2) (Janus kinase 1) (JAK-1) | Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16239216, ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:8232552}. |
| P25101 | EDNRA | S289 | psp | Endothelin-1 receptor (Endothelin receptor type A) (ET-A) (ETA-R) (hET-AR) | Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3. |
| P25705 | ATP5F1A | S419 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P26045 | PTPN3 | S419 | ochoa | Tyrosine-protein phosphatase non-receptor type 3 (EC 3.1.3.48) (Protein-tyrosine phosphatase H1) (PTP-H1) | May act at junctions between the membrane and the cytoskeleton. Possesses tyrosine phosphatase activity. |
| P27797 | CALR | S195 | ochoa | Calreticulin (CRP55) (Calregulin) (Endoplasmic reticulum resident protein 60) (ERp60) (HACBP) (grp60) | Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (PubMed:7876246). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity). {ECO:0000250|UniProtKB:P28491, ECO:0000250|UniProtKB:Q8K3H7, ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:7876246}. |
| P27816 | MAP4 | S1073 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P30291 | WEE1 | S312 | ochoa|psp | Wee1-like protein kinase (WEE1hu) (EC 2.7.10.2) (Wee1A kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15' (PubMed:15070733, PubMed:7743995, PubMed:8348613, PubMed:8428596). Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase (PubMed:7743995, PubMed:8348613, PubMed:8428596). Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur (PubMed:7743995, PubMed:8348613, PubMed:8428596). Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated (PubMed:7743995). A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation (PubMed:7743995). {ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:7743995, ECO:0000269|PubMed:8348613, ECO:0000269|PubMed:8428596}. |
| P30414 | NKTR | S1276 | ochoa | NK-tumor recognition protein (NK-TR protein) (Natural-killer cells cyclophilin-related protein) (Peptidyl-prolyl cis-trans isomerase NKTR) (PPIase) (EC 5.2.1.8) (Rotamase) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Component of a putative tumor-recognition complex involved in the function of NK cells (PubMed:8421688). {ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:8421688}. |
| P33240 | CSTF2 | S310 | ochoa | Cleavage stimulation factor subunit 2 (CF-1 64 kDa subunit) (Cleavage stimulation factor 64 kDa subunit) (CSTF 64 kDa subunit) (CstF-64) | One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs. {ECO:0000269|PubMed:32816001, ECO:0000269|PubMed:9199325}. |
| P35711 | SOX5 | S138 | ochoa | Transcription factor SOX-5 | Transcription factor involved in chondrocytes differentiation and cartilage formation. Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes, such as COL2A1 and AGC1. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX6, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene. {ECO:0000250|UniProtKB:P35710}. |
| P35712 | SOX6 | S126 | ochoa | Transcription factor SOX-6 | Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation (Probable). Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX5, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube. Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). {ECO:0000250|UniProtKB:P40645, ECO:0000305|PubMed:32442410}. |
| P37840 | SNCA | S87 | ochoa|psp | Alpha-synuclein (Non-A beta component of AD amyloid) (Non-A4 component of amyloid precursor) (NACP) | Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:20798282, PubMed:26442590, PubMed:28288128, PubMed:30404828). Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Also acts as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590). {ECO:0000269|PubMed:20798282, ECO:0000269|PubMed:26442590, ECO:0000269|PubMed:28288128, ECO:0000269|PubMed:30404828}. |
| P38398 | BRCA1 | S891 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P39880 | CUX1 | S409 | ochoa | Homeobox protein cut-like 1 (CCAAT displacement protein) (CDP) (CDP/Cux p200) (Homeobox protein cux-1) [Cleaved into: CDP/Cux p110] | Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}. |
| P40222 | TXLNA | S495 | ochoa | Alpha-taxilin | May be involved in intracellular vesicle traffic and potentially in calcium-dependent exocytosis in neuroendocrine cells. |
| P40818 | USP8 | S153 | ochoa | Ubiquitin carboxyl-terminal hydrolase 8 (EC 3.4.19.12) (Deubiquitinating enzyme 8) (Ubiquitin isopeptidase Y) (hUBPy) (Ubiquitin thioesterase 8) (Ubiquitin-specific-processing protease 8) | Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (PubMed:27302062). {ECO:0000269|PubMed:16520378, ECO:0000269|PubMed:17711858, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:27302062, ECO:0000269|PubMed:9628861}. |
| P46527 | CDKN1B | S83 | psp | Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1) | Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. {ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:28666995}. |
| P46531 | NOTCH1 | Y2145 | ochoa | Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). {ECO:0000269|PubMed:20616313}. |
| P46783 | RPS10 | S146 | ochoa | Small ribosomal subunit protein eS10 (40S ribosomal protein S10) | Component of the 40S ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). {ECO:0000269|PubMed:23636399}. |
| P47897 | QARS1 | S46 | ochoa | Glutamine--tRNA ligase (EC 6.1.1.18) (Glutaminyl-tRNA synthetase) (GlnRS) | Glutamine--tRNA ligase (PubMed:26869582). Plays a critical role in brain development (PubMed:24656866). {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}. |
| P49792 | RANBP2 | S1449 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P50851 | LRBA | S1231 | ochoa | Lipopolysaccharide-responsive and beige-like anchor protein (Beige-like protein) (CDC4-like protein) | Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). {ECO:0000250|UniProtKB:Q9ESE1, ECO:0000269|PubMed:33773106}. |
| P52657 | GTF2A2 | S61 | ochoa | Transcription initiation factor IIA subunit 2 (General transcription factor IIA subunit 2) (TFIIA p12 subunit) (TFIIA-12) (TFIIAS) (Transcription initiation factor IIA gamma chain) (TFIIA-gamma) | TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity. {ECO:0000269|PubMed:11030333}. |
| P53004 | BLVRA | S237 | ochoa|psp | Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) | Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}. |
| P54296 | MYOM2 | S555 | ochoa | Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P55854 | SUMO3 | S27 | ochoa | Small ubiquitin-related modifier 3 (SUMO-3) (SMT3 homolog 1) (SUMO-2) (Ubiquitin-like protein SMT3A) (Smt3A) | Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4 (PubMed:11451954, PubMed:18538659, PubMed:21965678). Plays a role in the regulation of sumoylation status of SETX (PubMed:24105744). {ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:21965678}. |
| P56856 | CLDN18 | S233 | ochoa | Claudin-18 | Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junction composition and therefore ion transport and solute permeability, potentially via downstream regulation of the actin cytoskeleton organization and beta-2-adrenergic signaling (By similarity). Required for lung alveolarization and maintenance of the paracellular alveolar epithelial barrier (By similarity). Acts to maintain epithelial progenitor cell proliferation and organ size, via regulation of YAP1 localization away from the nucleus and thereby restriction of YAP1 target gene transcription (By similarity). Acts as a negative regulator of RANKL-induced osteoclast differentiation, potentially via relocation of TJP2/ZO-2 away from the nucleus, subsequently involved in bone resorption in response to calcium deficiency (By similarity). Mediates the osteoprotective effects of estrogen, potentially via acting downstream of estrogen signaling independently of RANKL signaling pathways (By similarity). {ECO:0000250|UniProtKB:P56857}.; FUNCTION: [Isoform A1]: Involved in the maintenance of homeostasis of the alveolar microenvironment via regulation of pH and subsequent T-cell activation in the alveolar space, is therefore indirectly involved in limiting C.neoformans infection. {ECO:0000250|UniProtKB:P56857}.; FUNCTION: [Isoform A2]: Required for the formation of the gastric paracellular barrier via its role in tight junction formation, thereby involved in the response to gastric acidification. {ECO:0000250|UniProtKB:P56857}. |
| P57078 | RIPK4 | S434 | ochoa | Receptor-interacting serine/threonine-protein kinase 4 (EC 2.7.11.1) (Ankyrin repeat domain-containing protein 3) (PKC-delta-interacting protein kinase) | Serine/threonine protein kinase (By similarity). Required for embryonic skin development and correct skin homeostasis in adults, via phosphorylation of PKP1 and subsequent promotion of keratinocyte differentiation and cell adhesion (By similarity). It is a direct transcriptional target of TP63 (PubMed:22197488). Plays a role in NF-kappa-B activation (PubMed:12446564). {ECO:0000250|UniProtKB:Q9ERK0, ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:22197488}. |
| P60709 | ACTB | S344 | ochoa | Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] | Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}. |
| P63261 | ACTG1 | S344 | ochoa | Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}. |
| P78344 | EIF4G2 | S22 | ochoa | Eukaryotic translation initiation factor 4 gamma 2 (eIF-4-gamma 2) (eIF-4G 2) (eIF4G 2) (Death-associated protein 5) (DAP-5) (p97) | Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases. {ECO:0000269|PubMed:11511540, ECO:0000269|PubMed:11943866, ECO:0000269|PubMed:9032289, ECO:0000269|PubMed:9049310}. |
| P78527 | PRKDC | S861 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| Q00013 | MPP1 | S110 | ochoa | 55 kDa erythrocyte membrane protein (p55) (Membrane protein, palmitoylated 1) | Essential regulator of neutrophil polarity. Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity (By similarity). {ECO:0000250}. |
| Q00839 | HNRNPU | S59 | ochoa|psp | Heterogeneous nuclear ribonucleoprotein U (hnRNP U) (GRIP120) (Nuclear p120 ribonucleoprotein) (Scaffold-attachment factor A) (SAF-A) (p120) (pp120) | DNA- and RNA-binding protein involved in several cellular processes such as nuclear chromatin organization, telomere-length regulation, transcription, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing and mitotic cell progression (PubMed:10490622, PubMed:18082603, PubMed:19029303, PubMed:22325991, PubMed:25986610, PubMed:28622508). Plays a role in the regulation of interphase large-scale gene-rich chromatin organization through chromatin-associated RNAs (caRNAs) in a transcription-dependent manner, and thereby maintains genomic stability (PubMed:1324173, PubMed:28622508, PubMed:8174554). Required for the localization of the long non-coding Xist RNA on the inactive chromosome X (Xi) and the subsequent initiation and maintenance of X-linked transcriptional gene silencing during X-inactivation (By similarity). Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator (PubMed:10490622, PubMed:15711563, PubMed:19617346, PubMed:23811339, PubMed:8174554, PubMed:9353307). Promotes transcription initiation by direct association with the core-TFIIH basal transcription factor complex for the assembly of a functional pre-initiation complex with Pol II in a actin-dependent manner (PubMed:10490622, PubMed:15711563). Blocks Pol II transcription elongation activity by inhibiting the C-terminal domain (CTD) phosphorylation of Pol II and dissociates from Pol II pre-initiation complex prior to productive transcription elongation (PubMed:10490622). Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus (PubMed:19617346). Negatively regulates glucocorticoid-mediated transcriptional activation (PubMed:9353307). Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling (By similarity). Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression (PubMed:23811339). Participates in the circadian regulation of the core clock component BMAL1 transcription (By similarity). Plays a role in the regulation of telomere length (PubMed:18082603). Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis (PubMed:22325991). Plays a role in mRNA stability (PubMed:17174306, PubMed:17289661, PubMed:19029303). Component of the CRD-mediated complex that promotes MYC mRNA stabilization (PubMed:19029303). Enhances the expression of specific genes, such as tumor necrosis factor TNFA, by regulating mRNA stability, possibly through binding to the 3'-untranslated region (UTR) (PubMed:17174306). Plays a role in mitotic cell cycle regulation (PubMed:21242313, PubMed:25986610). Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression (PubMed:21242313). Phosphorylation at Ser-59 by PLK1 is required for chromosome alignement and segregation and progression through mitosis (PubMed:25986610). Also contributes to the targeting of AURKA to mitotic spindle MTs (PubMed:21242313). Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides (PubMed:1628625, PubMed:8068679, PubMed:8174554, PubMed:9204873, PubMed:9405365). Binds to chromatin-associated RNAs (caRNAs) (PubMed:28622508). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner (PubMed:10671544, PubMed:11003645, PubMed:11909954, PubMed:1324173, PubMed:28622508, PubMed:7509195, PubMed:9204873, PubMed:9405365). Binds to the Xist RNA (PubMed:26244333). Binds the long non-coding H19 RNA (PubMed:23811339). Binds to SMN1/2 pre-mRNAs at G/U-rich regions (PubMed:22325991). Binds to small nuclear RNAs (snRNAs) (PubMed:22325991). Binds to the 3'-UTR of TNFA mRNA (PubMed:17174306). Binds (via RNA-binding RGG-box region) to the long non-coding Xist RNA; this binding is direct and bridges the Xist RNA and the inactive chromosome X (Xi) (By similarity). Also negatively regulates embryonic stem cell differentiation upon LIF signaling (By similarity). Required for embryonic development (By similarity). Binds to brown fat long non-coding RNA 1 (Blnc1); facilitates the recruitment of Blnc1 by ZBTB7B required to drive brown and beige fat development and thermogenesis (By similarity). {ECO:0000250|UniProtKB:Q8VEK3, ECO:0000269|PubMed:10490622, ECO:0000269|PubMed:10671544, ECO:0000269|PubMed:11003645, ECO:0000269|PubMed:11909954, ECO:0000269|PubMed:1324173, ECO:0000269|PubMed:15711563, ECO:0000269|PubMed:1628625, ECO:0000269|PubMed:17174306, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:18082603, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19617346, ECO:0000269|PubMed:21242313, ECO:0000269|PubMed:22325991, ECO:0000269|PubMed:23811339, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26244333, ECO:0000269|PubMed:28622508, ECO:0000269|PubMed:7509195, ECO:0000269|PubMed:8068679, ECO:0000269|PubMed:8174554, ECO:0000269|PubMed:9204873, ECO:0000269|PubMed:9353307, ECO:0000269|PubMed:9405365}.; FUNCTION: (Microbial infection) Negatively regulates immunodeficiency virus type 1 (HIV-1) replication by preventing the accumulation of viral mRNA transcripts in the cytoplasm. {ECO:0000269|PubMed:16916646}. |
| Q06787 | FMR1 | S603 | ochoa | Fragile X messenger ribonucleoprotein 1 (Fragile X messenger ribonucleoprotein) (FMRP) (Protein FMR-1) | Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of target mRNAs (PubMed:12417522, PubMed:16631377, PubMed:18653529, PubMed:19166269, PubMed:23235829, PubMed:25464849). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:12417522, PubMed:30765518, PubMed:31439799). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Stabilizes the scaffolding postsynaptic density protein DLG4/PSD-95 and the myelin basic protein (MBP) mRNAs in hippocampal neurons and glial cells, respectively; this stabilization is further increased in response to metabotropic glutamate receptor (mGluR) stimulation (By similarity). Plays a role in selective delivery of a subset of dendritic mRNAs to synaptic sites in response to mGluR activation in a kinesin-dependent manner (By similarity). Undergoes liquid-liquid phase separation following phosphorylation and interaction with CAPRIN1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (PubMed:31439799). Acts as a repressor of mRNA translation in synaptic regions by mediating formation of neuronal ribonucleoprotein granules and promoting recruitmtent of EIF4EBP2 (PubMed:30765518). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postsynaptic dendritic spines (PubMed:11157796, PubMed:11532944, PubMed:12594214, PubMed:23235829). Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation initiation (By similarity). Represses mRNA translation by stalling ribosomal translocation during elongation (By similarity). Reports are contradictory with regards to its ability to mediate translation inhibition of MBP mRNA in oligodendrocytes (PubMed:23891804). Also involved in the recruitment of the RNA helicase MOV10 to a subset of mRNAs and hence regulates microRNA (miRNA)-mediated translational repression by AGO2 (PubMed:14703574, PubMed:17057366, PubMed:25464849). Facilitates the assembly of miRNAs on specific target mRNAs (PubMed:17057366). Also plays a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:19097999, PubMed:19166269). In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for local translation at synapses (By similarity). Binds to a large subset of dendritic mRNAs that encode a myriad of proteins involved in pre- and postsynaptic functions (PubMed:11157796, PubMed:11719189, PubMed:12594214, PubMed:17417632, PubMed:23235829, PubMed:24448548, PubMed:7692601). Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA consensus sequences within mRNA targets, mainly at coding sequence (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR (PubMed:23235829). Binds to intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (PubMed:11719189, PubMed:18579868, PubMed:25464849, PubMed:25692235). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (PubMed:11532944, PubMed:12594214, PubMed:15282548, PubMed:18653529, PubMed:7692601). Also binds to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (PubMed:15805463). Binds mRNAs containing U-rich target sequences (PubMed:12927206). Binds to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 mRNA (PubMed:19166269). Binds to the dendritic, small non-coding brain cytoplasmic RNA 1 (BC1); which may increase the association of the CYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses (By similarity). Plays a role in mRNA nuclear export (PubMed:31753916). Specifically recognizes and binds a subset of N6-methyladenosine (m6A)-containing mRNAs, promoting their nuclear export in a XPO1/CRM1-dependent manner (PubMed:31753916). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (By similarity). Associates with export factor NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (By similarity). Binds to a subset of miRNAs in the brain (PubMed:14703574, PubMed:17057366). May associate with nascent transcripts in a nuclear protein NXF1-dependent manner (PubMed:18936162). In vitro, binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:12950170, PubMed:15381419, PubMed:7688265, PubMed:7781595, PubMed:8156595). Moreover, plays a role in the modulation of the sodium-activated potassium channel KCNT1 gating activity (PubMed:20512134). Negatively regulates the voltage-dependent calcium channel current density in soma and presynaptic terminals of dorsal root ganglion (DRG) neurons, and hence regulates synaptic vesicle exocytosis (By similarity). Modulates the voltage-dependent calcium channel CACNA1B expression at the plasma membrane by targeting the channels for proteasomal degradation (By similarity). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (By similarity). Has been shown to play a translation-independent role in the modulation of presynaptic action potential (AP) duration and neurotransmitter release via large-conductance calcium-activated potassium (BK) channels in hippocampal and cortical excitatory neurons (PubMed:25561520). May be involved in the control of DNA damage response (DDR) mechanisms through the regulation of ATR-dependent signaling pathways such as histone H2AX/H2A.x and BRCA1 phosphorylations (PubMed:24813610). Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates (PubMed:39106863). {ECO:0000250|UniProtKB:P35922, ECO:0000250|UniProtKB:Q80WE1, ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:11532944, ECO:0000269|PubMed:11719189, ECO:0000269|PubMed:12417522, ECO:0000269|PubMed:12594214, ECO:0000269|PubMed:12927206, ECO:0000269|PubMed:12950170, ECO:0000269|PubMed:14703574, ECO:0000269|PubMed:15282548, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:17057366, ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:18579868, ECO:0000269|PubMed:18653529, ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:19097999, ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:20512134, ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:25692235, ECO:0000269|PubMed:30765518, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:31753916, ECO:0000269|PubMed:39106863, ECO:0000269|PubMed:7688265, ECO:0000269|PubMed:7692601, ECO:0000269|PubMed:7781595, ECO:0000269|PubMed:8156595}.; FUNCTION: [Isoform 10]: Binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). {ECO:0000269|PubMed:24204304}.; FUNCTION: [Isoform 6]: Binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). {ECO:0000269|PubMed:24204304}.; FUNCTION: (Microbial infection) Acts as a positive regulator of influenza A virus (IAV) replication. Required for the assembly and nuclear export of the viral ribonucleoprotein (vRNP) components. {ECO:0000269|PubMed:24514761}. |
| Q08378 | GOLGA3 | S272 | ochoa | Golgin subfamily A member 3 (Golgi complex-associated protein of 170 kDa) (GCP170) (Golgin-160) | Golgi auto-antigen; probably involved in maintaining Golgi structure. |
| Q12789 | GTF3C1 | S1073 | ochoa | General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) | Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element. |
| Q12802 | AKAP13 | S1849 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12851 | MAP4K2 | S367 | ochoa | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
| Q13085 | ACACA | S48 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13191 | CBLB | S282 | psp | E3 ubiquitin-protein ligase CBL-B (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene b) (RING finger protein 56) (RING-type E3 ubiquitin transferase CBL-B) (SH3-binding protein CBL-B) (Signal transduction protein CBL-B) | E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:Q3TTA7, ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}. |
| Q13263 | TRIM28 | S681 | ochoa | Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) | Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}. |
| Q13428 | TCOF1 | S734 | ochoa | Treacle protein (Treacher Collins syndrome protein) | Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}. |
| Q13523 | PRP4K | S507 | ochoa | Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) | Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}. |
| Q13651 | IL10RA | Y496 | psp | Interleukin-10 receptor subunit alpha (IL-10 receptor subunit alpha) (IL-10R subunit alpha) (IL-10RA) (CDw210a) (Interleukin-10 receptor subunit 1) (IL-10R subunit 1) (IL-10R1) (CD antigen CD210) | Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a conformational change in IL10RB, allowing IL10RB to bind IL10 as well (PubMed:16982608). In turn, the heterotetrameric assembly complex, composed of two subunits of IL10RA and IL10RB, activates the kinases JAK1 and TYK2 that are constitutively associated with IL10RA and IL10RB respectively (PubMed:12133952). These kinases then phosphorylate specific tyrosine residues in the intracellular domain in IL10RA leading to the recruitment and subsequent phosphorylation of STAT3. Once phosphorylated, STAT3 homodimerizes, translocates to the nucleus and activates the expression of anti-inflammatory genes. In addition, IL10RA-mediated activation of STAT3 inhibits starvation-induced autophagy (PubMed:26962683). {ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16982608, ECO:0000269|PubMed:26962683}. |
| Q14157 | UBAP2L | S360 | ochoa | Ubiquitin-associated protein 2-like (Protein NICE-4) (RNA polymerase II degradation factor UBAP2L) | Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). Plays an important role in the activity of long-term repopulating hematopoietic stem cells (LT-HSCs) (By similarity). Is a regulator of stress granule assembly, required for their efficient formation (PubMed:29395067, PubMed:35977029). Required for proper brain development and neocortex lamination (By similarity). {ECO:0000250|UniProtKB:Q80X50, ECO:0000269|PubMed:29395067, ECO:0000269|PubMed:35633597}. |
| Q14160 | SCRIB | S432 | ochoa | Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) | Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750, ECO:0000269|PubMed:27380321}. |
| Q14168 | MPP2 | S336 | ochoa | MAGUK p55 subfamily member 2 (Discs large homolog 2) (Protein MPP2) | Postsynaptic MAGUK scaffold protein that links CADM1 cell adhesion molecules to core components of the postsynaptic density (By similarity). In CA1 pyramidal neurons, required for synaptic KCNN2-containing channel function and long-term potentiation expression (By similarity). Seems to negatively regulate SRC function in epithelial cells (PubMed:19665017). {ECO:0000250|UniProtKB:D3ZAA9, ECO:0000250|UniProtKB:Q9WV34, ECO:0000269|PubMed:19665017}. |
| Q14289 | PTK2B | S361 | ochoa | Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) | Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. |
| Q15004 | PCLAF | S88 | ochoa | PCNA-associated factor (Hepatitis C virus NS5A-transactivated protein 9) (HCV NS5A-transactivated protein 9) (Overexpressed in anaplastic thyroid carcinoma 1) (OEATC-1) (PCNA-associated factor of 15 kDa) (PAF15) (p15PAF) (PCNA-clamp-associated factor) | PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with PCNA is disrupted, facilitating the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number. {ECO:0000269|PubMed:21673012, ECO:0000269|PubMed:23000965}. |
| Q15058 | KIF14 | S272 | ochoa | Kinesin-like protein KIF14 | Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}. |
| Q15233 | NONO | S212 | ochoa | Non-POU domain-containing octamer-binding protein (NonO protein) (54 kDa nuclear RNA- and DNA-binding protein) (p54(nrb)) (p54nrb) (55 kDa nuclear protein) (NMT55) (DNA-binding p52/p100 complex, 52 kDa subunit) | DNA- and RNA binding protein, involved in several nuclear processes (PubMed:11525732, PubMed:12403470, PubMed:26571461). Binds the conventional octamer sequence in double-stranded DNA (PubMed:11525732, PubMed:12403470, PubMed:26571461). Also binds single-stranded DNA and RNA at a site independent of the duplex site (PubMed:11525732, PubMed:12403470, PubMed:26571461). Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ (PubMed:11525732, PubMed:12403470, PubMed:26571461). Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b (PubMed:12403470). Together with PSPC1, required for the formation of nuclear paraspeckles (PubMed:22416126). The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs (PubMed:11525732). The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1 (PubMed:10858305). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends (PubMed:15590677). In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex (PubMed:15590677). NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (PubMed:11897684). NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (By similarity). Important for the functional organization of GABAergic synapses (By similarity). Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript (By similarity). Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728, PubMed:30270045). Promotes activation of the cGAS-STING pathway in response to HIV-2 infection: acts by interacting with HIV-2 Capsid protein p24, thereby promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation (PubMed:30270045). In contrast, the weak interaction with HIV-1 Capsid protein p24 does not allow activation of the cGAS-STING pathway (PubMed:30270045). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:12403470, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:30270045}. |
| Q15596 | NCOA2 | S671 | ochoa | Nuclear receptor coactivator 2 (NCoA-2) (Class E basic helix-loop-helix protein 75) (bHLHe75) (Transcriptional intermediary factor 2) (hTIF2) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:22504882, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:26553876, ECO:0000269|PubMed:8670870, ECO:0000269|PubMed:9430642}. |
| Q15722 | LTB4R | S320 | ochoa|psp | Leukotriene B4 receptor 1 (LTB4-R 1) (LTB4-R1) (Chemoattractant receptor-like 1) (G-protein coupled receptor 16) (P2Y purinoceptor 7) (P2Y7) | Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y receptor involved in the regulation of cardiac muscle contraction through modulation of L-type calcium currents. Is a receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response. |
| Q16143 | SNCB | S42 | ochoa | Beta-synuclein | Non-amyloid component of senile plaques found in Alzheimer disease. Could act as a regulator of SNCA aggregation process. Protects neurons from staurosporine and 6-hydroxy dopamine (6OHDA)-stimulated caspase activation in a p53/TP53-dependent manner. Contributes to restore the SNCA anti-apoptotic function abolished by 6OHDA. Not found in the Lewy bodies associated with Parkinson disease. |
| Q16665 | HIF1A | S727 | psp | Hypoxia-inducible factor 1-alpha (HIF-1-alpha) (HIF1-alpha) (ARNT-interacting protein) (Basic-helix-loop-helix-PAS protein MOP1) (Class E basic helix-loop-helix protein 78) (bHLHe78) (Member of PAS protein 1) (PAS domain-containing protein 8) | Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:16543236, PubMed:9887100). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}. |
| Q17RH5 | RAPGEF2 | S921 | psp | Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (Neural RAP guanine nucleotide exchange protein) (PDZ domain-containing guanine nucleotide exchange factor 1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) | None |
| Q1W6H9 | FAM110C | S241 | ochoa | Protein FAM110C | May play a role in microtubule organization. May play a role in cell spreading and cell migration of epithelial cells; the function may involve the AKT1 signaling pathway. {ECO:0000269|PubMed:17499476, ECO:0000269|PubMed:19698782}. |
| Q2M3G4 | SHROOM1 | S291 | ochoa | Protein Shroom1 (Apical protein 2) | May be involved in the assembly of microtubule arrays during cell elongation. {ECO:0000250}. |
| Q2NKX8 | ERCC6L | S984 | ochoa | DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) | DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}. |
| Q3ZCQ8 | TIMM50 | S45 | ochoa | Mitochondrial import inner membrane translocase subunit TIM50 | Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane (PubMed:30190335, PubMed:38828998). Has some phosphatase activity in vitro; however such activity may not be relevant in vivo. {ECO:0000269|PubMed:15044455, ECO:0000269|PubMed:30190335, ECO:0000269|PubMed:38828998}.; FUNCTION: [Isoform 2]: May participate in the release of snRNPs and SMN from the Cajal body. {ECO:0000269|PubMed:16008839}. |
| Q5JSP0 | FGD3 | S68 | ochoa | FYVE, RhoGEF and PH domain-containing protein 3 (Zinc finger FYVE domain-containing protein 5) | Promotes the formation of filopodia. May activate CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape (By similarity). {ECO:0000250}. |
| Q5SR56 | MFSD14B | S468 | ochoa | Hippocampus abundant transcript-like protein 1 (Major facilitator superfamily domain-containing 14B) | None |
| Q5T0W9 | FAM83B | S563 | ochoa | Protein FAM83B | Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. {ECO:0000269|PubMed:22886302, ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:23912460}. |
| Q5T3J3 | LRIF1 | S502 | ochoa | Ligand-dependent nuclear receptor-interacting factor 1 (HP1-binding protein enriched in inactive X chromosome protein 1) (HBiX1) (Receptor-interacting factor 1) | Together with SMCHD1, involved in chromosome X inactivation in females by promoting the compaction of heterochromatin (PubMed:23542155). Also able to repress the ligand-induced transcriptional activity of retinoic acid receptor alpha (RARA), possibly through direct recruitment of histone deacetylases (PubMed:17455211). Also required for silencing of the DUX4 locus in somatic cells (PubMed:32467133). {ECO:0000269|PubMed:17455211, ECO:0000269|PubMed:23542155, ECO:0000269|PubMed:32467133}. |
| Q5T8D3 | ACBD5 | S444 | ochoa | Acyl-CoA-binding domain-containing protein 5 | Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters. {ECO:0000269|PubMed:24535825}. |
| Q5T8P6 | RBM26 | S92 | ochoa | RNA-binding protein 26 (CTCL tumor antigen se70-2) (RNA-binding motif protein 26) | May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}. |
| Q5THJ4 | VPS13D | S926 | ochoa | Intermembrane lipid transfer protein VPS13D (Vacuolar protein sorting-associated protein 13D) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Functions in promoting mitochondrial clearance by mitochondrial autophagy (mitophagy), also possibly by positively regulating mitochondrial fission (PubMed:29307555, PubMed:29604224). Mitophagy plays an important role in regulating cell health and mitochondrial size and homeostasis. {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:29307555, ECO:0000269|PubMed:29604224}. |
| Q5VST9 | OBSCN | S4015 | ochoa | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q5VZ89 | DENND4C | S1601 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5W0B1 | OBI1 | S595 | ochoa | ORC ubiquitin ligase 1 (OBI1) (EC 2.3.2.27) (RING finger protein 219) | E3 ubiquitin ligase essential for DNA replication origin activation during S phase (PubMed:31160578). Acts as a replication origin selector which selects the origins to be fired and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase (PubMed:31160578). {ECO:0000269|PubMed:31160578}. |
| Q63ZY3 | KANK2 | S147 | ochoa | KN motif and ankyrin repeat domain-containing protein 2 (Ankyrin repeat domain-containing protein 25) (Matrix-remodeling-associated protein 3) (SRC-1-interacting protein) (SIP) (SRC-interacting protein) (SRC1-interacting protein) | Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3 (PubMed:17476305). Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria (PubMed:22371500). Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis (PubMed:22371500). Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081). Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway (PubMed:17996375, PubMed:25961457). May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney (PubMed:25961457). Through the Rho signaling pathway may also regulate cell proliferation (By similarity). {ECO:0000250|UniProtKB:Q8BX02, ECO:0000269|PubMed:17476305, ECO:0000269|PubMed:17996375, ECO:0000269|PubMed:22371500, ECO:0000269|PubMed:24671081, ECO:0000269|PubMed:25961457}. |
| Q641Q2 | WASHC2A | S877 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q68CZ2 | TNS3 | S352 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q68DK7 | MSL1 | S371 | ochoa | Male-specific lethal 1 homolog (MSL-1) (Male-specific lethal 1-like 1) (MSL1-like 1) (Male-specific lethal-1 homolog 1) | Non-catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at 'Lys-16' (H4K16ac), an epigenetic mark that prevents chromatin compaction (PubMed:16227571, PubMed:16543150, PubMed:33837287). The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac (PubMed:33837287). The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome (By similarity). X up-regulation is required to compensate for autosomal biallelic expression (By similarity). The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA (By similarity). Within the MSL complex, acts as a scaffold to tether MSL3 and KAT8 together for enzymatic activity regulation (PubMed:22547026). Greatly enhances MSL2 E3 ubiquitin ligase activity, promoting monoubiquitination of histone H2B at 'Lys-34' (H2BK34Ub) (PubMed:21726816, PubMed:30930284). This modification in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (PubMed:21726816). {ECO:0000250|UniProtKB:Q6PDM1, ECO:0000269|PubMed:16227571, ECO:0000269|PubMed:16543150, ECO:0000269|PubMed:21726816, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:30930284, ECO:0000269|PubMed:33837287}. |
| Q6DKI7 | PVRIG | S284 | ochoa | Transmembrane protein PVRIG (CD112 receptor) (CD112R) (Poliovirus receptor-related immunoglobulin domain-containing protein) | Cell surface receptor for NECTIN2. May act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals. Following interaction with NECTIN2, inhibits T-cell proliferation. Competes with CD226 for NECTIN2-binding. {ECO:0000269|PubMed:26755705}. |
| Q6IQ55 | TTBK2 | S371 | ochoa | Tau-tubulin kinase 2 (EC 2.7.11.1) | Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). Required for recruitment of CPLANE2 and INTU to the mother centriole (By similarity). {ECO:0000250|UniProtKB:Q3UVR3, ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541, ECO:0000269|PubMed:30375385}. |
| Q6NZI2 | CAVIN1 | S127 | ochoa | Caveolae-associated protein 1 (Cavin-1) (Polymerase I and transcript release factor) | Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues (PubMed:18056712, PubMed:18191225, PubMed:19726876). Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1). Essential for normal oligomerization of CAV1. Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop. Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template (By similarity) (PubMed:18056712, PubMed:18191225, PubMed:19726876). The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A (By similarity). {ECO:0000250|UniProtKB:O54724, ECO:0000269|PubMed:18056712, ECO:0000269|PubMed:18191225, ECO:0000269|PubMed:19726876}. |
| Q6P2E9 | EDC4 | S672 | ochoa | Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) | In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}. |
| Q6P3S6 | FBXO42 | S488 | ochoa | F-box only protein 42 (Just one F-box and Kelch domain-containing protein) | Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Specifically recognizes p53/TP53, promoting its ubiquitination and degradation. {ECO:0000269|PubMed:19509332}. |
| Q6P4Q7 | CNNM4 | S688 | ochoa | Metal transporter CNNM4 (Ancient conserved domain-containing protein 4) (Cyclin-M4) | Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function. {ECO:0000250, ECO:0000269|PubMed:19200525, ECO:0000269|PubMed:19200527}. |
| Q6P996 | PDXDC1 | S695 | ochoa | Pyridoxal-dependent decarboxylase domain-containing protein 1 (EC 4.1.1.-) | None |
| Q6PCB5 | RSBN1L | S39 | ochoa | Lysine-specific demethylase RSBN1L (EC 1.14.11.-) (Round spermatid basic protein 1-like protein) | Lysine-specific demethylase that specifically demethylates methylated lysine residues of proteins. {ECO:0000250|UniProtKB:Q80T69}. |
| Q6PJI9 | WDR59 | S830 | ochoa | GATOR2 complex protein WDR59 (WD repeat-containing protein 59) | As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:25457612, PubMed:27487210, PubMed:35831510, PubMed:36528027, PubMed:36577058). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:27487210, PubMed:35831510, PubMed:36528027). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25457612, PubMed:27487210). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027, ECO:0000269|PubMed:36577058}. |
| Q6VY07 | PACS1 | S423 | ochoa | Phosphofurin acidic cluster sorting protein 1 (PACS-1) | Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin-coated membrane pits. Involved in HIV-1 nef-mediated removal of MHC-I from the cell surface to the TGN. Required for normal ER Ca2+ handling in lymphocytes. Together with WDR37, it plays an essential role in lymphocyte development, quiescence and survival. Required for stabilizing peripheral lymphocyte populations (By similarity). {ECO:0000250|UniProtKB:Q8K212, ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:15692563}. |
| Q6WKZ4 | RAB11FIP1 | S758 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6WKZ4 | RAB11FIP1 | S1135 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6ZMU5 | TRIM72 | S189 | ochoa | Tripartite motif-containing protein 72 (EC 2.3.2.27) (Mitsugumin-53) (Mg53) | Muscle-specific E3 ubiquitin-protein ligase that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites (PubMed:36944613). Its ubiquitination activity is mediated by E2 ubiquitin-conjugating enzymes UBE2D1, UBE2D2 and UBE2D3 (By similarity). Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site (By similarity). This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation (By similarity). Probably acts upstream of the Ca(2+)-dependent membrane resealing process (By similarity). Required for transport of DYSF to sites of cell injury during repair patch formation (By similarity). Regulates membrane budding and exocytosis (By similarity). May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles (By similarity). {ECO:0000250|UniProtKB:Q1XH17, ECO:0000269|PubMed:36944613}. |
| Q6ZVF9 | GPRIN3 | S517 | ochoa | G protein-regulated inducer of neurite outgrowth 3 (GRIN3) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q70E73 | RAPH1 | S1183 | ochoa | Ras-associated and pleckstrin homology domains-containing protein 1 (RAPH1) (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 18 protein) (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 9 protein) (Lamellipodin) (Proline-rich EVH1 ligand 2) (PREL-2) (Protein RMO1) | Mediator of localized membrane signals. Implicated in the regulation of lamellipodial dynamics. Negatively regulates cell adhesion. |
| Q70EL1 | USP54 | S1158 | ochoa | Ubiquitin carboxyl-terminal hydrolase 54 (EC 3.4.19.12) (Ubiquitin-specific peptidase 54) | Deubiquitinase that specifically mediates 'Lys-63'-linked deubiquitination of substrates with a polyubiquitin chain composed of at least 3 ubiquitins (PubMed:39587316). Specifically recognizes ubiquitin chain in position S2 and catalyzes cleavage of polyubiquitin within 'Lys-63'-linked chains (PubMed:39587316). Not able to deubiquitinate substrates with shorter ubiquitin chains (PubMed:39587316). Mediates deubiquitination of PLK4, maintaining PLK4 stability by reducing its ubiquitination-mediated degradation (PubMed:36590171). {ECO:0000269|PubMed:36590171, ECO:0000269|PubMed:39587316}. |
| Q76N89 | HECW1 | S874 | ochoa | E3 ubiquitin-protein ligase HECW1 (EC 2.3.2.26) (HECT, C2 and WW domain-containing protein 1) (HECT-type E3 ubiquitin transferase HECW1) (NEDD4-like E3 ubiquitin-protein ligase 1) (hNEDL1) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1. Also targets the mutant SOD1 protein involved in familial amyotrophic lateral sclerosis (FALS). Forms cytotoxic aggregates with DVL1, SSR3 and mutant SOD1 that lead to motor neuron death in FALS. {ECO:0000269|PubMed:14684739}. |
| Q7L2J0 | MEPCE | S342 | ochoa | 7SK snRNA methylphosphate capping enzyme (MePCE) (EC 2.1.1.-) (Bicoid-interacting protein 3 homolog) (Bin3 homolog) | S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA (7SK RNA), leading to stabilize it (PubMed:17643375, PubMed:19906723, PubMed:30559425). Also has a non-enzymatic function as part of the 7SK RNP complex: the 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:17643375). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838). In the 7SK RNP complex, MEPCE is required to stabilize 7SK RNA and facilitate the assembly of 7SK RNP complex (PubMed:19906723, PubMed:38100593). MEPCE has a non-enzymatic function in the 7SK RNP complex; interaction with LARP7 within the 7SK RNP complex occluding its catalytic center (PubMed:19906723). Also required for stability of U6 snRNAs (PubMed:38100593). {ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:19906723, ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:30559425, ECO:0000269|PubMed:38100593}. |
| Q7LDG7 | RASGRP2 | S560 | ochoa | RAS guanyl-releasing protein 2 (Calcium and DAG-regulated guanine nucleotide exchange factor I) (CalDAG-GEFI) (Cdc25-like protein) (hCDC25L) (F25B3.3 kinase-like protein) | Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. {ECO:0000269|PubMed:10918068, ECO:0000269|PubMed:14702343, ECO:0000269|PubMed:17576779, ECO:0000269|PubMed:17702895, ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135}. |
| Q7RTS9 | DYM | S510 | ochoa | Dymeclin (Dyggve-Melchior-Clausen syndrome protein) | Necessary for correct organization of Golgi apparatus. Involved in bone development. {ECO:0000269|PubMed:21280149}. |
| Q7Z2K8 | GPRIN1 | S608 | ochoa | G protein-regulated inducer of neurite outgrowth 1 (GRIN1) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q7Z2W4 | ZC3HAV1 | S390 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z3G6 | PRICKLE2 | S319 | ochoa | Prickle-like protein 2 | None |
| Q7Z4H7 | HAUS6 | S524 | ochoa | HAUS augmin-like complex subunit 6 | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q7Z6I6 | ARHGAP30 | S632 | ochoa | Rho GTPase-activating protein 30 (Rho-type GTPase-activating protein 30) | GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42. {ECO:0000269|PubMed:21565175}. |
| Q7Z6J2 | TAMALIN | T77 | ochoa | Protein TAMALIN (General receptor for phosphoinositides 1-associated scaffold protein) (GRP1-associated scaffold protein) | Plays a role in intracellular trafficking and contributes to the macromolecular organization of group 1 metabotropic glutamate receptors (mGluRs) at synapses. {ECO:0000250}. |
| Q7Z6Z7 | HUWE1 | S2534 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S3158 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z739 | YTHDF3 | S23 | ochoa | YTH domain-containing family protein 3 (DF3) | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28106072, PubMed:28106076, PubMed:28281539, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:28106072, PubMed:28281539, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3 (PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:28106076, PubMed:32492408). Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs (By similarity). Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification (By similarity). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (PubMed:28106072). Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (PubMed:28281539). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31292544, PubMed:31388144, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation (PubMed:32194978). {ECO:0000250|UniProtKB:Q8BYK6, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:28106076, ECO:0000269|PubMed:28281539, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:32194978, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: Has some antiviral activity against HIV-1 virus: incorporated into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity in the next cycle of infection (PubMed:32053707). May interfere with this early step of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome (PubMed:32053707). {ECO:0000269|PubMed:32053707}. |
| Q7Z7G8 | VPS13B | S105 | ochoa | Intermembrane lipid transfer protein VPS13B (Cohen syndrome protein 1) (Vacuolar protein sorting-associated protein 13B) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phosphatidylinositol 3-phosphate (By similarity). Functions as a tethering factor in the slow endocytic recycling pathway, to assist traffic between early and recycling endosomes (PubMed:24334764, PubMed:30962439, PubMed:32375900). Involved in the transport of proacrosomal vesicles to the nuclear dense lamina (NDL) during spermatid development (By similarity). Plays a role in the assembly of the Golgi apparatus, possibly by mediating trafficking to the Golgi membrane (PubMed:21865173). Plays a role in the development of the nervous system, and may be required for neuron projection development (PubMed:25492866, PubMed:32560273). May also play a role during adipose tissue development (PubMed:26358774). Required for maintenance of the ocular lens (By similarity). {ECO:0000250|UniProtKB:Q07878, ECO:0000250|UniProtKB:Q80TY5, ECO:0000269|PubMed:21865173, ECO:0000269|PubMed:24334764, ECO:0000269|PubMed:26358774, ECO:0000269|PubMed:30962439, ECO:0000269|PubMed:32375900, ECO:0000269|PubMed:32560273, ECO:0000305|PubMed:25492866, ECO:0000305|PubMed:32560273}. |
| Q86SQ0 | PHLDB2 | S524 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86T90 | KIAA1328 | S490 | ochoa | Protein hinderin | Competes with SMC1 for binding to SMC3. May affect the availability of SMC3 to engage in the formation of multimeric protein complexes. {ECO:0000269|PubMed:15656913}. |
| Q86UD5 | SLC9B2 | S49 | ochoa | Sodium/hydrogen exchanger 9B2 (Na(+)/H(+) exchanger NHA2) (Na(+)/H(+) exchanger-like domain-containing protein 2) (NHE domain-containing protein 2) (Sodium/hydrogen exchanger-like domain-containing protein 2) (Solute carrier family 9 subfamily B member 2) | Electroneutral Na(+) Li(+)/H(+) antiporter that extrudes Na(+) or Li(+) in exchange for external protons across the membrane (PubMed:18000046, PubMed:18508966, PubMed:22948142, PubMed:28154142, PubMed:36177733). Uses the proton gradient/membrane potential to extrude sodium (PubMed:22948142). Contributes to the regulation of intracellular pH and sodium homeostasis (By similarity). Also able to mediate Na(+)/Li(+) antiporter activity in kidney (PubMed:22948142). May play a physiological role in renal tubular function and blood pressure homeostasis (By similarity). Plays an important role for insulin secretion and clathrin-mediated endocytosis in beta-cells (By similarity). Involved in sperm motility and fertility (By similarity). It is controversial whether SLC9B2 plays a role in osteoclast differentiation or not (By similarity). {ECO:0000250|UniProtKB:Q5BKR2, ECO:0000269|PubMed:18000046, ECO:0000269|PubMed:18508966, ECO:0000269|PubMed:22948142, ECO:0000269|PubMed:28154142, ECO:0000269|PubMed:36177733}. |
| Q86UE4 | MTDH | S216 | ochoa | Protein LYRIC (3D3/LYRIC) (Astrocyte elevated gene-1 protein) (AEG-1) (Lysine-rich CEACAM1 co-isolated protein) (Metadherin) (Metastasis adhesion protein) | Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance. {ECO:0000269|PubMed:15927426, ECO:0000269|PubMed:16452207, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:19111877}. |
| Q86UE4 | MTDH | S351 | ochoa | Protein LYRIC (3D3/LYRIC) (Astrocyte elevated gene-1 protein) (AEG-1) (Lysine-rich CEACAM1 co-isolated protein) (Metadherin) (Metastasis adhesion protein) | Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance. {ECO:0000269|PubMed:15927426, ECO:0000269|PubMed:16452207, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:19111877}. |
| Q86UE8 | TLK2 | S44 | ochoa | Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) | Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}. |
| Q86UT8 | CENATAC | S182 | ochoa | Centrosomal AT-AC splicing factor (Coiled-coil domain-containing protein 84) | Component of the minor spliceosome that promotes splicing of a specific, rare minor intron subtype (PubMed:34009673). Negative regulator of centrosome duplication (PubMed:31722219). Constrains centriole number by modulating the degradation of the centrosome-duplication-associated protein SASS6 in an acetylation-dependent manner. SIRT1 deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly. The CENATAC acetylation level is restored in mitosis by NAT10, promoting SASS6 proteasome degradation by facilitating SASS6 binding to APC/C E3 ubiquitin-protein ligase complex/FZR1 (PubMed:31722219). {ECO:0000269|PubMed:31722219, ECO:0000269|PubMed:34009673}. |
| Q86V48 | LUZP1 | S518 | ochoa | Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) | F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}. |
| Q8IW52 | SLITRK4 | S663 | ochoa | SLIT and NTRK-like protein 4 | It is involved in synaptogenesis and promotes synapse differentiation (PubMed:27812321). Suppresses neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q810B8, ECO:0000269|PubMed:27812321}. |
| Q8IWC1 | MAP7D3 | S169 | ochoa | MAP7 domain-containing protein 3 | Promotes the assembly and stability of microtubules. {ECO:0000269|PubMed:22142902, ECO:0000269|PubMed:24927501}. |
| Q8IWY9 | CDAN1 | S285 | ochoa | Codanin-1 | May act as a negative regulator of ASF1 in chromatin assembly. {ECO:0000269|PubMed:22407294}. |
| Q8IXT5 | RBM12B | S377 | ochoa | RNA-binding protein 12B (RNA-binding motif protein 12B) | None |
| Q8IYD9 | LAS2 | S161 | ochoa | Lung adenoma susceptibility protein 2 | Might play a role in cell proliferation. {ECO:0000250}. |
| Q8N5S9 | CAMKK1 | S82 | ochoa | Calcium/calmodulin-dependent protein kinase kinase 1 (CaM-KK 1) (CaM-kinase kinase 1) (CaMKK 1) (EC 2.7.11.17) (CaM-kinase IV kinase) (Calcium/calmodulin-dependent protein kinase kinase alpha) (CaM-KK alpha) (CaM-kinase kinase alpha) (CaMKK alpha) | Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. {ECO:0000269|PubMed:12935886}. |
| Q8NCY6 | MSANTD4 | S137 | ochoa | Myb/SANT-like DNA-binding domain-containing protein 4 (Myb/SANT-like DNA-binding domain containing 4 with coiled-coils) | None |
| Q8NDV7 | TNRC6A | S878 | ochoa | Trinucleotide repeat-containing gene 6A protein (CAG repeat protein 26) (EMSY interactor protein) (GW182 autoantigen) (Protein GW1) (Glycine-tryptophan protein of 182 kDa) | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As a scaffolding protein, associates with argonaute proteins bound to partially complementary mRNAs, and can simultaneously recruit CCR4-NOT and PAN deadenylase complexes. {ECO:0000269|PubMed:16284622, ECO:0000269|PubMed:16284623, ECO:0000269|PubMed:17596515, ECO:0000269|PubMed:17671087, ECO:0000269|PubMed:19056672, ECO:0000269|PubMed:19304925}. |
| Q8NEM0 | MCPH1 | S548 | ochoa | Microcephalin | Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex. {ECO:0000269|PubMed:12046007, ECO:0000269|PubMed:15199523, ECO:0000269|PubMed:15220350}. |
| Q8NET4 | RTL9 | S1039 | ochoa | Retrotransposon Gag-like protein 9 (Retrotransposon gag domain-containing protein 1) (Tumor antigen BJ-HCC-23) | None |
| Q8NEY1 | NAV1 | S490 | ochoa | Neuron navigator 1 (Pore membrane and/or filament-interacting-like protein 3) (Steerin-1) (Unc-53 homolog 1) (unc53H1) | May be involved in neuronal migration. {ECO:0000250}. |
| Q8NFT2 | STEAP2 | S194 | ochoa | Metalloreductase STEAP2 (EC 1.16.1.-) (Prostate cancer-associated protein 1) (Protein up-regulated in metastatic prostate cancer) (PUMPCn) (Six-transmembrane epithelial antigen of prostate 2) (SixTransMembrane protein of prostate 1) | Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane (By similarity). Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (By similarity). Can also reduce Cu(2+) to Cu(1+) (By similarity). {ECO:0000250|UniProtKB:Q687X5, ECO:0000250|UniProtKB:Q8BWB6}. |
| Q8TDC0 | MYOZ3 | S49 | ochoa | Myozenin-3 (Calsarcin-3) (FATZ-related protein 3) | Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis. |
| Q8WUM0 | NUP133 | S489 | ochoa | Nuclear pore complex protein Nup133 (133 kDa nucleoporin) (Nucleoporin Nup133) | Involved in poly(A)+ RNA transport. Involved in nephrogenesis (PubMed:30179222). {ECO:0000269|PubMed:11684705, ECO:0000269|PubMed:30179222}. |
| Q8WUZ0 | BCL7C | S106 | ochoa | B-cell CLL/lymphoma 7 protein family member C | May play an anti-apoptotic role. {ECO:0000250}. |
| Q8WXE9 | STON2 | S272 | ochoa | Stonin-2 (Stoned B) | Adapter protein involved in endocytic machinery. Involved in the synaptic vesicle recycling. May facilitate clathrin-coated vesicle uncoating. {ECO:0000269|PubMed:11381094, ECO:0000269|PubMed:11454741, ECO:0000269|PubMed:21102408}. |
| Q8WXG6 | MADD | S762 | ochoa | MAP kinase-activating death domain protein (Differentially expressed in normal and neoplastic cells) (Insulinoma glucagonoma clone 20) (Rab3 GDP/GTP exchange factor) (RabGEF) (Rab3 GDP/GTP exchange protein) (Rab3GEP) | Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064). {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q80U28, ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:32761064, ECO:0000269|PubMed:9115275}. |
| Q8WY36 | BBX | S822 | ochoa | HMG box transcription factor BBX (Bobby sox homolog) (HMG box-containing protein 2) | Transcription factor that is necessary for cell cycle progression from G1 to S phase. {ECO:0000269|PubMed:11680820}. |
| Q8WYL5 | SSH1 | S583 | ochoa | Protein phosphatase Slingshot homolog 1 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 1) (SSH-1L) (hSSH-1L) | Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. {ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12684437, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:14531860, ECO:0000269|PubMed:14645219, ECO:0000269|PubMed:15056216, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:16230460}. |
| Q8WYL5 | SSH1 | S894 | ochoa | Protein phosphatase Slingshot homolog 1 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 1) (SSH-1L) (hSSH-1L) | Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. {ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12684437, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:14531860, ECO:0000269|PubMed:14645219, ECO:0000269|PubMed:15056216, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:16230460}. |
| Q92576 | PHF3 | S702 | ochoa | PHD finger protein 3 | None |
| Q92585 | MAML1 | S344 | ochoa | Mastermind-like protein 1 (Mam-1) | Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}. |
| Q92614 | MYO18A | S2002 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q96CP6 | GRAMD1A | S586 | ochoa | Protein Aster-A (GRAM domain-containing protein 1A) | Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). May play a role in tumor progression (By similarity). Plays a role in autophagy regulation and is required for biogenesis of the autophagosome (PubMed:31222192). This function in autophagy requires its cholesterol-transfer activity (PubMed:31222192). {ECO:0000250|UniProtKB:Q8VEF1, ECO:0000269|PubMed:31222192}. |
| Q96CX2 | KCTD12 | S151 | ochoa | BTB/POZ domain-containing protein KCTD12 (Pfetin) (Predominantly fetal expressed T1 domain) | Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). {ECO:0000250}. |
| Q96EX2 | RNFT2 | S125 | ochoa | E3 ubiquitin-protein ligase RNFT2 (RING finger and transmembrane domain-containing protein 2) (Transmembrane protein 118) | E3 ubiquitin-protein ligase that negatively regulates IL3-dependent cellular responses through IL3RA ubiquitination and degradation by the proteasome, having an anti-inflammatory effect. {ECO:0000269|PubMed:31990690}. |
| Q96FL8 | SLC47A1 | S23 | ochoa | Multidrug and toxin extrusion protein 1 (MATE-1) (hMATE-1) (Solute carrier family 47 member 1) | Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). {ECO:0000269|PubMed:16330770, ECO:0000269|PubMed:17495125, ECO:0000269|PubMed:17509534, ECO:0000269|PubMed:17582384, ECO:0000269|PubMed:18305230, ECO:0000269|PubMed:19158817, ECO:0000269|PubMed:21128598, ECO:0000269|PubMed:24961373, ECO:0000305|PubMed:35307651}. |
| Q96G01 | BICD1 | S548 | ochoa | Protein bicaudal D homolog 1 (Bic-D 1) | Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport by recruiting the dynein-dynactin motor complex. |
| Q96GG9 | DCUN1D1 | S59 | ochoa | DCN1-like protein 1 (DCNL1) (DCUN1 domain-containing protein 1) (Defective in cullin neddylation protein 1-like protein 1) (Squamous cell carcinoma-related oncogene) | Part of an E3 ubiquitin ligase complex for neddylation (PubMed:18826954). Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (PubMed:19617556, PubMed:23201271, PubMed:23401859, PubMed:26906416). Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (PubMed:25349211, PubMed:28581483). Also acts as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity). {ECO:0000250|UniProtKB:Q9QZ73, ECO:0000269|PubMed:18826954, ECO:0000269|PubMed:19617556, ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:23401859, ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26906416, ECO:0000269|PubMed:28581483}. |
| Q96HC4 | PDLIM5 | S134 | ochoa | PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) | May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}. |
| Q96IQ7 | VSIG2 | S281 | ochoa | V-set and immunoglobulin domain-containing protein 2 (Cortical thymocyte-like protein) (CT-like protein) | None |
| Q96MK2 | RIPOR3 | S340 | ochoa | RIPOR family member 3 | None |
| Q99490 | AGAP2 | S638 | ochoa | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 (AGAP-2) (Centaurin-gamma-1) (Cnt-g1) (GTP-binding and GTPase-activating protein 2) (GGAP2) (Phosphatidylinositol 3-kinase enhancer) (PIKE) | GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion. {ECO:0000269|PubMed:12640130, ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15118108, ECO:0000269|PubMed:16079295}. |
| Q99569 | PKP4 | S139 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99570 | PIK3R4 | S755 | ochoa | Phosphoinositide 3-kinase regulatory subunit 4 (PI3-kinase regulatory subunit 4) (EC 2.7.11.1) (PI3-kinase p150 subunit) (Phosphoinositide 3-kinase adaptor protein) | Regulatory subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123). {ECO:0000269|PubMed:20643123}. |
| Q99613 | EIF3C | S865 | ochoa | Eukaryotic translation initiation factor 3 subunit C (eIF3c) (Eukaryotic translation initiation factor 3 subunit 8) (eIF3 p110) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03002, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| Q99626 | CDX2 | S179 | ochoa | Homeobox protein CDX-2 (CDX-3) (Caudal-type homeobox protein 2) | Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium (By similarity). Binds to the promoter of the intestinal sucrase-isomaltase SI and activates SI transcription (By similarity). Binds to the DNA sequence 5'-ATAAAAACTTAT-3' in the promoter region of VDR and activates VDR transcription (By similarity). Binds to and activates transcription of LPH (By similarity). Activates transcription of CLDN2 and intestinal mucin MUC2 (By similarity). Binds to the 5'-AATTTTTTACAACACCT-3' DNA sequence in the promoter region of CA1 and activates CA1 transcription (By similarity). Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000250|UniProtKB:P43241, ECO:0000250|UniProtKB:Q04649, ECO:0000269|PubMed:28473536}. |
| Q99698 | LYST | S1054 | ochoa | Lysosomal-trafficking regulator (Beige homolog) | Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (PubMed:11984006, PubMed:25216107). Might regulate trafficking of effectors involved in exocytosis (PubMed:25425525). In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules (PubMed:26478006). In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes (By similarity). In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways (PubMed:27881733). {ECO:0000250|UniProtKB:P97412, ECO:0000269|PubMed:11984006, ECO:0000269|PubMed:25216107, ECO:0000269|PubMed:25425525, ECO:0000269|PubMed:26478006, ECO:0000269|PubMed:27881733}. |
| Q99856 | ARID3A | S357 | ochoa | AT-rich interactive domain-containing protein 3A (ARID domain-containing protein 3A) (B-cell regulator of IgH transcription) (Bright) (Dead ringer-like protein 1) (E2F-binding protein 1) | Transcription factor which may be involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation. {ECO:0000269|PubMed:11812999, ECO:0000269|PubMed:12692263}. |
| Q99959 | PKP2 | S650 | ochoa | Plakophilin-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297). {ECO:0000250|UniProtKB:F1M7L9, ECO:0000250|UniProtKB:Q9CQ73, ECO:0000269|PubMed:18662195, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:22781308, ECO:0000269|PubMed:23884246, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:28169297, ECO:0000269|PubMed:34368962, ECO:0000269|PubMed:35959657}. |
| Q9BQ61 | TRIR | S111 | ochoa | Telomerase RNA component interacting RNase (EC 3.1.13.-) (Exoribonuclease TRIR) | Exoribonuclease that is part of the telomerase RNA 3' end processing complex and which has the ability to cleave all four unpaired RNA nucleotides from the 5' end or 3' end with higher efficiency for purine bases (PubMed:28322335). {ECO:0000269|PubMed:28322335}. |
| Q9BR76 | CORO1B | S443 | ochoa | Coronin-1B (Coronin-2) | Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity). {ECO:0000250, ECO:0000269|PubMed:16027158}. |
| Q9BSQ5 | CCM2 | S181 | ochoa | Cerebral cavernous malformations 2 protein (Malcavernin) | Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity). {ECO:0000250}. |
| Q9BUZ4 | TRAF4 | S426 | ochoa|psp | TNF receptor-associated factor 4 (EC 2.3.2.27) (Cysteine-rich domain associated with RING and Traf domains protein 1) (Metastatic lymph node gene 62 protein) (MLN 62) (RING finger protein 83) | Adapter protein with E3 ligase activity that is involved in many diverse biological processes including cell proliferation, migration, differentiation, DNA repair, platelet activation or apoptosis (PubMed:30352854, PubMed:31076633, PubMed:32268273, PubMed:33991522). Promotes EGFR-mediated signaling by facilitating the dimerization of EGFR and downstream AKT activation thereby promoting cell proliferation (PubMed:30352854). Ubiquitinates SMURF2 through 'Lys-48'-linked ubiquitin chain leading to SMURF2 degradation through the proteasome and subsequently osteogenic differentiation (PubMed:31076633). Promotes 'Lys-63'-mediated ubiquitination of CHK1 which in turn activates cell cycle arrest and activation of DNA repair (PubMed:32357935). In addition, promotes an atypical 'Lys-29'-linked ubiquitination at the C-terminal end of IRS1 which is crucial for insulin-like growth factor (IGF) signal transduction (PubMed:33991522). Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions. Inhibits adipogenic differentiation by activating pyruvate kinase PKM activity and subsequently the beta-catenin signaling pathway (PubMed:32268273). {ECO:0000250, ECO:0000269|PubMed:12023963, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:16052631, ECO:0000269|PubMed:16157600, ECO:0000269|PubMed:18953416, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:30352854, ECO:0000269|PubMed:31076633, ECO:0000269|PubMed:32268273, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33991522}. |
| Q9BV73 | CEP250 | S2322 | ochoa | Centrosome-associated protein CEP250 (250 kDa centrosomal protein) (Cep250) (Centrosomal Nek2-associated protein 1) (C-Nap1) (Centrosomal protein 2) | Plays an important role in centrosome cohesion during interphase (PubMed:30404835, PubMed:36282799). Recruits CCDC102B to the proximal ends of centrioles (PubMed:30404835). Maintains centrosome cohesion by forming intercentriolar linkages (PubMed:36282799). Accumulates at the proximal end of each centriole, forming supramolecular assemblies with viscous material properties that promote organelle cohesion (PubMed:36282799). May be involved in ciliogenesis (PubMed:28005958). {ECO:0000269|PubMed:28005958, ECO:0000269|PubMed:30404835, ECO:0000269|PubMed:36282799}. |
| Q9BXF6 | RAB11FIP5 | S566 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BY11 | PACSIN1 | S346 | ochoa|psp | Protein kinase C and casein kinase substrate in neurons protein 1 (Syndapin-1) | Plays a role in the reorganization of the microtubule cytoskeleton via its interaction with MAPT; this decreases microtubule stability and inhibits MAPT-induced microtubule polymerization. Plays a role in cellular transport processes by recruiting DNM1, DNM2 and DNM3 to membranes. Plays a role in the reorganization of the actin cytoskeleton and in neuron morphogenesis via its interaction with COBL and WASL, and by recruiting COBL to the cell cortex. Plays a role in the regulation of neurite formation, neurite branching and the regulation of neurite length. Required for normal synaptic vesicle endocytosis; this process retrieves previously released neurotransmitters to accommodate multiple cycles of neurotransmission. Required for normal excitatory and inhibitory synaptic transmission (By similarity). Binds to membranes via its F-BAR domain and mediates membrane tubulation. {ECO:0000250, ECO:0000269|PubMed:19549836, ECO:0000269|PubMed:22573331, ECO:0000269|PubMed:23236520}. |
| Q9BYW2 | SETD2 | S705 | ochoa | Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) | Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. |
| Q9GZR1 | SENP6 | S606 | ochoa | Sentrin-specific protease 6 (EC 3.4.22.-) (SUMO-1-specific protease 1) (Sentrin/SUMO-specific protease SENP6) | Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Also desumoylates RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. {ECO:0000269|PubMed:16912044, ECO:0000269|PubMed:17000875, ECO:0000269|PubMed:18799455, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20705237, ECO:0000269|PubMed:21148299}. |
| Q9H2X9 | SLC12A5 | S963 | psp | Solute carrier family 12 member 5 (Electroneutral potassium-chloride cotransporter 2) (K-Cl cotransporter 2) (hKCC2) (Neuronal K-Cl cotransporter) | Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (PubMed:12106695). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262). {ECO:0000250|UniProtKB:Q63633, ECO:0000269|PubMed:12106695, ECO:0000269|PubMed:24668262}. |
| Q9H329 | EPB41L4B | S401 | ochoa | Band 4.1-like protein 4B (Erythrocyte membrane protein band 4.1-like 4B) (FERM-containing protein CG1) (Protein EHM2) | Up-regulates the activity of the Rho guanine nucleotide exchange factor ARHGEF18 (By similarity). Involved in the regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950). Promotes cellular adhesion, migration and motility in vitro and may play a role in wound healing (PubMed:23664528). May have a role in mediating cytoskeletal changes associated with steroid-induced cell differentiation (PubMed:14521927). {ECO:0000250|UniProtKB:Q9JMC8, ECO:0000269|PubMed:14521927, ECO:0000269|PubMed:22006950, ECO:0000269|PubMed:23664528}. |
| Q9H4I2 | ZHX3 | S708 | ochoa | Zinc fingers and homeoboxes protein 3 (Triple homeobox protein 1) (Zinc finger and homeodomain protein 3) | Acts as a transcriptional repressor. Involved in the early stages of mesenchymal stem cell (MSC) osteogenic differentiation. Is a regulator of podocyte gene expression during primary glomerula disease. Binds to promoter DNA. {ECO:0000269|PubMed:12659632, ECO:0000269|PubMed:21174497}. |
| Q9H4L5 | OSBPL3 | S262 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H6A9 | PCNX3 | S244 | ochoa | Pecanex-like protein 3 (Pecanex homolog protein 3) | None |
| Q9H6R7 | WDCP | S510 | ochoa | WD repeat and coiled-coil-containing protein | None |
| Q9H900 | ZWILCH | S572 | ochoa | Protein zwilch homolog (hZwilch) | Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (PubMed:15824131). {ECO:0000269|PubMed:15824131}. |
| Q9HB71 | CACYBP | S141 | ochoa|psp | Calcyclin-binding protein (CacyBP) (hCacyBP) (S100A6-binding protein) (Siah-interacting protein) | May be involved in calcium-dependent ubiquitination and subsequent proteasomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1). {ECO:0000269|PubMed:16085652}. |
| Q9HDC5 | JPH1 | S220 | ochoa | Junctophilin-1 (JP-1) (Junctophilin type 1) | Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes. |
| Q9NPA3 | MID1IP1 | S75 | ochoa | Mid1-interacting protein 1 (Gastrulation-specific G12-like protein) (Mid1-interacting G12-like protein) (Protein STRAIT11499) (Spot 14-related protein) (S14R) (Spot 14-R) | Plays a role in the regulation of lipogenesis in liver. Up-regulates ACACA enzyme activity. Required for efficient lipid biosynthesis, including triacylglycerol, diacylglycerol and phospholipid. Involved in stabilization of microtubules (By similarity). {ECO:0000250}. |
| Q9NQ39 | RPS10P5 | S157 | ochoa | Putative ribosomal protein eS10-like (Putative 40S ribosomal protein S10-like) | None |
| Q9NQU5 | PAK6 | S236 | ochoa | Serine/threonine-protein kinase PAK 6 (EC 2.7.11.1) (PAK-5) (p21-activated kinase 6) (PAK-6) | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Also inhibits ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}. |
| Q9NQW7 | XPNPEP1 | S556 | ochoa | Xaa-Pro aminopeptidase 1 (EC 3.4.11.9) (Aminoacylproline aminopeptidase) (Cytosolic aminopeptidase P) (Soluble aminopeptidase P) (sAmp) (X-Pro aminopeptidase 1) (X-prolyl aminopeptidase 1, soluble) | Metalloaminopeptidase that catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro (PubMed:11106490, PubMed:18515364, PubMed:35165443). Contributes to the degradation of bradykinin (PubMed:11106490). {ECO:0000269|PubMed:11106490, ECO:0000269|PubMed:18515364, ECO:0000269|PubMed:35165443}. |
| Q9NUE0 | ZDHHC18 | S61 | ochoa | Palmitoyltransferase ZDHHC18 (EC 2.3.1.225) (DHHC domain-containing cysteine-rich protein 18) (DHHC-18) (Zinc finger DHHC domain-containing protein 18) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates, such as CGAS, HRAS and LCK (PubMed:23034182, PubMed:27481942, PubMed:35438208). Acts as a negative regulator of the cGAS-STING pathway be mediating palmitoylation and inactivation of CGAS (PubMed:35438208). May also have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and therefore regulate G protein-coupled receptor signaling (PubMed:27481942). {ECO:0000269|PubMed:23034182, ECO:0000269|PubMed:27481942, ECO:0000269|PubMed:35438208}. |
| Q9NUQ8 | ABCF3 | S161 | ochoa | ATP-binding cassette sub-family F member 3 | Displays an antiviral effect against flaviviruses such as west Nile virus (WNV) in the presence of OAS1B. {ECO:0000250}. |
| Q9NV58 | RNF19A | S69 | ochoa | E3 ubiquitin-protein ligase RNF19A (EC 2.3.2.31) (Double ring-finger protein) (Dorfin) (RING finger protein 19A) (p38) | E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR. Specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation and to neuronal protection. {ECO:0000269|PubMed:11237715, ECO:0000269|PubMed:12145308, ECO:0000269|PubMed:12750386, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16513638}. |
| Q9NXR5 | ANKRD10 | S347 | ochoa | Ankyrin repeat domain-containing protein 10 | None |
| Q9NY59 | SMPD3 | S291 | ochoa | Sphingomyelin phosphodiesterase 3 (EC 3.1.4.12) (Neutral sphingomyelinase 2) (nSMase-2) (nSMase2) (Neutral sphingomyelinase II) | Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization (PubMed:10823942, PubMed:14741383, PubMed:15051724). Binds to anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) that modulate enzymatic activity and subcellular location. May be involved in IL-1-beta-induced JNK activation in hepatocytes (By similarity). May act as a mediator in transcriptional regulation of NOS2/iNOS via the NF-kappa-B activation under inflammatory conditions (By similarity). {ECO:0000250|UniProtKB:O35049, ECO:0000250|UniProtKB:Q9JJY3, ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:14741383, ECO:0000269|PubMed:15051724}. |
| Q9NYV4 | CDK12 | S1379 | ochoa | Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) | Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| Q9NZB2 | FAM120A | S925 | ochoa | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q9P212 | PLCE1 | S67 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (EC 3.1.4.11) (Pancreas-enriched phospholipase C) (Phosphoinositide phospholipase C-epsilon-1) (Phospholipase C-epsilon-1) (PLC-epsilon-1) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690). {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, ECO:0000269|PubMed:29058690}. |
| Q9P265 | DIP2B | S153 | ochoa | Disco-interacting protein 2 homolog B (DIP2 homolog B) | Negatively regulates axonal outgrowth and is essential for normal synaptic transmission. Not required for regulation of axon polarity. Promotes acetylation of alpha-tubulin. {ECO:0000250|UniProtKB:Q3UH60}. |
| Q9P2F8 | SIPA1L2 | S1552 | ochoa | Signal-induced proliferation-associated 1-like protein 2 (SIPA1-like protein 2) | None |
| Q9P2G1 | ANKIB1 | S443 | ochoa | Ankyrin repeat and IBR domain-containing protein 1 (EC 2.3.2.31) | Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. {ECO:0000250}. |
| Q9P2Y5 | UVRAG | S571 | ochoa|psp | UV radiation resistance-associated gene protein (p63) | Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P) (PubMed:16799551, PubMed:18552835, PubMed:20643123, PubMed:24056303, PubMed:28306502). During autophagy acts as a regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3 (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502). Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2 (PubMed:16799551, PubMed:20643123, PubMed:24056303). Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events (PubMed:18552835, PubMed:28306502). Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion (PubMed:24550300). In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly (PubMed:24550300). {ECO:0000269|PubMed:18552835, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:24056303, ECO:0000269|PubMed:28306502, ECO:0000305}.; FUNCTION: Involved in maintaining chromosomal stability. Promotes DNA double-strand break (DSB) repair by association with DNA-dependent protein kinase complex DNA-PK and activating it in non-homologous end joining (NHEJ) (PubMed:22542840). Required for centrosome stability and proper chromosome segregation (PubMed:22542840). {ECO:0000269|PubMed:22542840}. |
| Q9UBU7 | DBF4 | S357 | ochoa | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UBY5 | LPAR3 | S335 | ochoa | Lysophosphatidic acid receptor 3 (LPA receptor 3) (LPA-3) (Lysophosphatidic acid receptor Edg-7) | Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. May play a role in the development of ovarian cancer. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins. |
| Q9UGH3 | SLC23A2 | S81 | ochoa | Solute carrier family 23 member 2 (Na(+)/L-ascorbic acid transporter 2) (Nucleobase transporter-like 1 protein) (Sodium-dependent vitamin C transporter 2) (hSVCT2) (Yolk sac permease-like molecule 2) | Sodium/ascorbate cotransporter (PubMed:10471399, PubMed:10556521). Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate (PubMed:10471399). {ECO:0000269|PubMed:10471399, ECO:0000269|PubMed:10556521}. |
| Q9UGU0 | TCF20 | S810 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UHB7 | AFF4 | S161 | ochoa | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UKI2 | CDC42EP3 | S115 | ochoa | Cdc42 effector protein 3 (Binder of Rho GTPases 2) (MSE55-related Cdc42-binding protein) | Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts. {ECO:0000269|PubMed:10490598, ECO:0000269|PubMed:11035016}. |
| Q9UKI8 | TLK1 | S103 | ochoa | Serine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (PKU-beta) (Tousled-like kinase 1) | Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}. |
| Q9UKJ3 | GPATCH8 | S637 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKX7 | NUP50 | S115 | ochoa | Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) | Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}. |
| Q9ULU4 | ZMYND8 | S1126 | ochoa | MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) | Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}. |
| Q9ULV4 | CORO1C | S187 | ochoa | Coronin-1C (Coronin-3) (hCRNN4) | Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1 (PubMed:25074804, PubMed:25925950). Increases the presence of activated RAC1 at the leading edge of migrating cells (PubMed:25074804, PubMed:25925950). Required for normal organization of the cytoskeleton, including the actin cytoskeleton, microtubules and the vimentin intermediate filaments (By similarity). Plays a role in endoplasmic reticulum-associated endosome fission: localizes to endosome membrane tubules and promotes recruitment of TMCC1, leading to recruitment of the endoplasmic reticulum to endosome tubules for fission (PubMed:30220460). Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane (PubMed:30220460). Required for normal cell proliferation, cell migration, and normal formation of lamellipodia (By similarity). Required for normal distribution of mitochondria within cells (By similarity). {ECO:0000250|UniProtKB:Q9WUM4, ECO:0000269|PubMed:25074804, ECO:0000269|PubMed:25925950, ECO:0000269|PubMed:30220460, ECO:0000269|PubMed:34106209}.; FUNCTION: [Isoform 3]: Involved in myogenic differentiation. {ECO:0000269|PubMed:19651142}. |
| Q9ULW0 | TPX2 | S654 | ochoa | Targeting protein for Xklp2 (Differentially expressed in cancerous and non-cancerous lung cells 2) (DIL-2) (Hepatocellular carcinoma-associated antigen 519) (Hepatocellular carcinoma-associated antigen 90) (Protein fls353) (Restricted expression proliferation-associated protein 100) (p100) | Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules (PubMed:18663142, PubMed:19208764, PubMed:37728657). Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation (PubMed:18663142, PubMed:19208764). TPX2 is inactivated upon binding to importin-alpha (PubMed:26165940). At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation (PubMed:26165940). {ECO:0000269|PubMed:18663142, ECO:0000269|PubMed:19208764, ECO:0000269|PubMed:26165940}. |
| Q9UP65 | PLA2G4C | S337 | ochoa | Cytosolic phospholipase A2 gamma (cPLA2-gamma) (EC 3.1.1.4) (Cytosolic lysophospholipase) (EC 3.1.1.5) (Cytosolic lysophospholipid O-acyltransferase) (EC 2.3.1.-) (Phospholipase A2 group IVC) | Calcium-independent phospholipase, lysophospholipase and O-acyltransferase involved in phospholipid remodeling with implications in endoplasmic reticulum membrane homeostasis and lipid droplet biogenesis (PubMed:10085124, PubMed:10358058, PubMed:19501189, PubMed:28336330, PubMed:9705332). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at the sn-2 position of phospholipids with choline and ethanolamine head groups, producing lysophospholipids that are used in deacylation-reacylation cycles (PubMed:10085124, PubMed:10358058, PubMed:19501189, PubMed:28336330, PubMed:9705332). Transfers the sn-1 fatty acyl from one lysophospholipid molecule to the sn-2 position of another lysophospholipid to form diacyl, alkylacyl and alkenylacyl glycerophospholipids. Cleaves ester bonds but not alkyl or alkenyl ether bonds at sn-1 position of lysophospholipids (PubMed:15944408, PubMed:19501189). Catalyzes sn-2 fatty acyl transfer from phospholipids to the sn-2 position of 1-O-alkyl or 1-O-alkenyl lysophospholipids with lower efficiency (PubMed:15944408, PubMed:19501189). In response to dietary fatty acids, may play a role in the formation of nascent lipid droplets from the endoplasmic reticulum likely by regulating the phospholipid composition of these organelles (PubMed:28336330). {ECO:0000269|PubMed:10085124, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:15944408, ECO:0000269|PubMed:19501189, ECO:0000269|PubMed:28336330, ECO:0000269|PubMed:9705332}.; FUNCTION: (Microbial infection) May play a role in replication and assembly of human hepatitis C virus (HCV) (PubMed:23015700, PubMed:28336330). In response to HCV infection, promotes remodeling of host endoplasmic reticulum membranes to form organelle-like structures called membranous web, where HCV replication occur (PubMed:23015700). Can further mediate translocation of replication complexes to lipid droplets to enable virion assembly (PubMed:23015700, PubMed:28336330). {ECO:0000269|PubMed:23015700, ECO:0000269|PubMed:28336330}.; FUNCTION: (Microbial infection) May facilitate human T-lymphotropic virus type 1 (HTLV-1) infection by promoting leukotriene B4 (LTB4) biosynthesis. LTB4 acts as a chemoattractant for HTLV-1-infected CD4-positive T cells and favors cell to cell viral transmission. {ECO:0000269|PubMed:28639618}. |
| Q9UPN4 | CEP131 | S35 | ochoa|psp | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9UPN4 | CEP131 | S221 | ochoa | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9UPN4 | CEP131 | S247 | ochoa | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9UPQ0 | LIMCH1 | S898 | ochoa | LIM and calponin homology domains-containing protein 1 | Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration. {ECO:0000269|PubMed:28228547}. |
| Q9Y2K6 | USP20 | S304 | ochoa | Ubiquitin carboxyl-terminal hydrolase 20 (EC 3.4.19.12) (Deubiquitinating enzyme 20) (Ubiquitin thioesterase 20) (Ubiquitin-specific-processing protease 20) (VHL-interacting deubiquitinating enzyme 2) (hVDU2) | Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis (PubMed:27801882, PubMed:29487085). Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination (PubMed:26839314). Promotes cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'-linked ubiquitination of STING1 leading to its stabilization (PubMed:27801882). Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1 (PubMed:29487085). Acts as a positive regulator for NF-kappa-B activation by TNF-alpha through deubiquitinating 'Lys-48'-linked polyubiquitination of SQSTM1, leading to its increased stability (PubMed:32354117). Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2) (PubMed:19424180). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2 (PubMed:19424180). This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity (PubMed:15776016). Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability (PubMed:35063767). Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol (PubMed:33792613). {ECO:0000269|PubMed:12056827, ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:15776016, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:26839314, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:33792613, ECO:0000269|PubMed:35063767}. |
| Q9Y2X7 | GIT1 | S514 | ochoa | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y333 | LSM2 | S65 | ochoa | U6 snRNA-associated Sm-like protein LSm2 (Protein G7b) (Small nuclear ribonuclear protein D homolog) (snRNP core Sm-like protein Sm-x5) | Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320). {ECO:0000269|PubMed:10523320, ECO:0000269|PubMed:28781166}. |
| Q9Y4E8 | USP15 | S630 | ochoa | Ubiquitin carboxyl-terminal hydrolase 15 (EC 3.4.19.12) (Deubiquitinating enzyme 15) (Ubiquitin thioesterase 15) (Ubiquitin-specific-processing protease 15) (Unph-2) (Unph4) | Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004, PubMed:21947082, PubMed:22344298, PubMed:24852371). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:33093067). May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19576224, PubMed:19826004). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9 (PubMed:33093067). {ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689, ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:33093067}.; FUNCTION: (Microbial infection) Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway. {ECO:0000269|PubMed:19553310}. |
| Q9Y4F5 | CEP170B | S492 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y4F5 | CEP170B | S941 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y4F5 | CEP170B | S1040 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y4G8 | RAPGEF2 | S933 | ochoa | Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) | Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}. |
| Q9Y561 | LRP12 | S617 | ochoa | Low-density lipoprotein receptor-related protein 12 (LDLR-related protein 12) (LRP-12) (Suppressor of tumorigenicity 7 protein) | Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. May act as a tumor suppressor. {ECO:0000269|PubMed:12809483}. |
| Q9Y5B9 | SUPT16H | S360 | ochoa | FACT complex subunit SPT16 (Chromatin-specific transcription elongation factor 140 kDa subunit) (FACT 140 kDa subunit) (FACTp140) (Facilitates chromatin transcription complex subunit SPT16) (hSPT16) | Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9836642}. |
| Q9Y6D6 | ARFGEF1 | S1079 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (Brefeldin A-inhibited GEP 1) (ADP-ribosylation factor guanine nucleotide-exchange factor 1) (p200 ARF guanine nucleotide exchange factor) (p200 ARF-GEP1) | Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturation of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competitive RhoA binding. The function in the nucleus remains to be determined. {ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15644318, ECO:0000269|PubMed:17227842, ECO:0000269|PubMed:20360857, ECO:0000269|PubMed:22084092}. |
| Q06124 | PTPN11 | S134 | Sugiyama | Tyrosine-protein phosphatase non-receptor type 11 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1D) (PTP-1D) (Protein-tyrosine phosphatase 2C) (PTP-2C) (SH-PTP2) (SHP-2) (Shp2) (SH-PTP3) | Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:14739280, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity). Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L (PubMed:19275884). {ECO:0000250|UniProtKB:P35235, ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:14739280, ECO:0000269|PubMed:18559669, ECO:0000269|PubMed:18829466, ECO:0000269|PubMed:19275884, ECO:0000269|PubMed:26742426, ECO:0000269|PubMed:28074573}. |
| O00444 | PLK4 | S443 | Sugiyama | Serine/threonine-protein kinase PLK4 (EC 2.7.11.21) (Polo-like kinase 4) (PLK-4) (Serine/threonine-protein kinase 18) (Serine/threonine-protein kinase Sak) | Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:30804208}. |
| P78417 | GSTO1 | S23 | Sugiyama | Glutathione S-transferase omega-1 (GSTO-1) (EC 2.5.1.18) (Glutathione S-transferase omega 1-1) (GSTO 1-1) (Glutathione-dependent dehydroascorbate reductase) (EC 1.8.5.1) (Monomethylarsonic acid reductase) (MMA(V) reductase) (EC 1.20.4.2) (S-(Phenacyl)glutathione reductase) (SPG-R) | Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Also has glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. {ECO:0000269|PubMed:10783391, ECO:0000269|PubMed:11511179, ECO:0000269|PubMed:17226937, ECO:0000269|PubMed:18028863, ECO:0000269|PubMed:21106529}. |
| Q8TF68 | ZNF384 | S114 | Sugiyama | Zinc finger protein 384 (CAG repeat protein 1) (CAS-interacting zinc finger protein) (Nuclear matrix transcription factor 4) (Nuclear matrix protein 4) (Trinucleotide repeat-containing gene 1 protein) | Transcription factor that binds the consensus DNA sequence [GC]AAAAA. Seems to bind and regulate the promoters of MMP1, MMP3, MMP7 and COL1A1 (By similarity). {ECO:0000250}. |
| O00507 | USP9Y | S647 | Sugiyama | Ubiquitin carboxyl-terminal hydrolase 9Y (EC 3.4.19.12) (Deubiquitinating enzyme FAF-Y) (Fat facets protein-related, Y-linked) (Ubiquitin thioesterase FAF-Y) (Ubiquitin-specific protease 9, Y chromosome) (Ubiquitin-specific-processing protease FAF-Y) | Deubiquitinase that mediates deubiquitination of target proteins (PubMed:12895410). May stabilize target proteins that are important for male germ cell development (PubMed:12895410). {ECO:0000269|PubMed:12895410}. |
| Q7Z7G1 | CLNK | S331 | Sugiyama | Cytokine-dependent hematopoietic cell linker (Mast cell immunoreceptor signal transducer) | An adapter protein which plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation (By similarity). Together with FGR, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity). Acts as a positive regulator of both T-cell receptor and natural killer T (NKT) cell receptor signaling in CD4-positive NKT cells (By similarity). Together with MAP4K1, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity). May be involved in tumor necrosis factor induced cell death by promoting reactive oxidative species generation, and MLKL oligomerization, ultimately leading to necrosis (By similarity). Involved in phosphorylation of LAT (By similarity). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (By similarity). {ECO:0000250|UniProtKB:Q9QZE2}. |
| Q5SSJ5 | HP1BP3 | S227 | Sugiyama | Heterochromatin protein 1-binding protein 3 (Protein HP1-BP74) | Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity (PubMed:24830416). Mediates chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance and self-renewal (PubMed:25100860). {ECO:0000269|PubMed:24830416, ECO:0000269|PubMed:25100860}. |
| O15460 | P4HA2 | Y79 | Sugiyama | Prolyl 4-hydroxylase subunit alpha-2 (4-PH alpha-2) (EC 1.14.11.2) (Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-2) | Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. {ECO:0000269|PubMed:9211872}. |
| Q15067 | ACOX1 | Y239 | Sugiyama | Peroxisomal acyl-coenzyme A oxidase 1 (AOX) (EC 1.3.3.6) (Palmitoyl-CoA oxidase) (Peroxisomal fatty acyl-CoA oxidase) (Straight-chain acyl-CoA oxidase) (SCOX) [Cleaved into: Peroxisomal acyl-CoA oxidase 1, A chain; Peroxisomal acyl-CoA oxidase 1, B chain; Peroxisomal acyl-CoA oxidase 1, C chain] | Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids (PubMed:15060085, PubMed:17458872, PubMed:17603022, PubMed:32169171, PubMed:33234382, PubMed:7876265). Catalyzes the desaturation of fatty acyl-CoAs such as palmitoyl-CoA (hexadecanoyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs) such as (2E)-hexadecenoyl-CoA, and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)) (PubMed:17458872, PubMed:17603022, PubMed:7876265). {ECO:0000269|PubMed:15060085, ECO:0000269|PubMed:17458872, ECO:0000269|PubMed:17603022, ECO:0000269|PubMed:32169171, ECO:0000269|PubMed:33234382, ECO:0000269|PubMed:7876265}.; FUNCTION: [Isoform 1]: Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro. {ECO:0000269|PubMed:17603022}.; FUNCTION: [Isoform 2]: Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs. {ECO:0000269|PubMed:17603022}. |
| Q14203 | DCTN1 | S31 | Sugiyama | Dynactin subunit 1 (150 kDa dynein-associated polypeptide) (DAP-150) (DP-150) (p135) (p150-glued) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020). {ECO:0000250|UniProtKB:A0A287B8J2, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23386061, ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25774020}. |
| Q99426 | TBCB | S163 | Sugiyama | Tubulin-folding cofactor B (Cytoskeleton-associated protein 1) (Cytoskeleton-associated protein CKAPI) (Tubulin-specific chaperone B) | Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer (PubMed:9265649). Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth (By similarity). {ECO:0000250|UniProtKB:Q9D1E6, ECO:0000269|PubMed:9265649}. |
| Q6UVK1 | CSPG4 | S321 | Sugiyama | Chondroitin sulfate proteoglycan 4 (Chondroitin sulfate proteoglycan NG2) (Melanoma chondroitin sulfate proteoglycan) (Melanoma-associated chondroitin sulfate proteoglycan) | Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis. May also inhibit neurite outgrowth and growth cone collapse during axon regeneration. Cell surface receptor for collagen alpha 2(VI) which may confer cells ability to migrate on that substrate. Binds through its extracellular N-terminus growth factors, extracellular matrix proteases modulating their activity. May regulate MPP16-dependent degradation and invasion of type I collagen participating in melanoma cells invasion properties. May modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. Also functions as a signal transducing protein by binding through its cytoplasmic C-terminus scaffolding and signaling proteins. May promote retraction fiber formation and cell polarization through Rho GTPase activation. May stimulate alpha-4, beta-1 integrin-mediated adhesion and spreading by recruiting and activating a signaling cascade through CDC42, ACK1 and BCAR1. May activate FAK and ERK1/ERK2 signaling cascades. {ECO:0000269|PubMed:10587647, ECO:0000269|PubMed:11278606, ECO:0000269|PubMed:15210734}. |
| P35368 | ADRA1B | S396 | SIGNOR|iPTMNet|EPSD | Alpha-1B adrenergic receptor (Alpha-1B adrenoreceptor) (Alpha-1B adrenoceptor) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P24723 | PRKCH | S599 | Sugiyama | Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}. |
| O95456 | PSMG1 | S183 | Sugiyama | Proteasome assembly chaperone 1 (PAC-1) (Chromosome 21 leucine-rich protein) (C21-LRP) (Down syndrome critical region protein 2) (Proteasome chaperone homolog 1) (Pba1) | Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization. {ECO:0000269|PubMed:16251969, ECO:0000269|PubMed:17707236}. |
| Q15349 | RPS6KA2 | S425 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q13043 | STK4 | S43 | Sugiyama | Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. |
| Q13188 | STK3 | S40 | Sugiyama | Serine/threonine-protein kinase 3 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 2) (MST-2) (STE20-like kinase MST2) (Serine/threonine-protein kinase Krs-1) [Cleaved into: Serine/threonine-protein kinase 3 36kDa subunit (MST2/N); Serine/threonine-protein kinase 3 20kDa subunit (MST2/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation (PubMed:11278283, PubMed:8566796, PubMed:8816758). Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714, PubMed:29063833, PubMed:30622739). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714). STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250 (PubMed:21076410, PubMed:21723128). In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (PubMed:21104395). Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259' (PubMed:20212043). Phosphorylates MOBKL1A and RASSF2 (PubMed:19525978). Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 (PubMed:18328708, PubMed:18362890). {ECO:0000250|UniProtKB:Q9JI10, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:20212043, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:21723128, ECO:0000269|PubMed:23972470, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:8566796, ECO:0000269|PubMed:8816758}. |
| Q16512 | PKN1 | S374 | SIGNOR|EPSD|Sugiyama | Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) | PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. |
| P10636 | MAPT | S622 | SIGNOR | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| Q7KZI7 | MARK2 | S633 | Sugiyama | Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}. |
| P60520 | GABARAPL2 | S39 | Sugiyama | Gamma-aminobutyric acid receptor-associated protein-like 2 (GABA(A) receptor-associated protein-like 2) (Ganglioside expression factor 2) (GEF-2) (General protein transport factor p16) (Golgi-associated ATPase enhancer of 16 kDa) (GATE-16) (MAP1 light chain 3-related protein) | Ubiquitin-like modifier involved in intra-Golgi traffic (By similarity). Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation (By similarity). It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy (PubMed:20418806, PubMed:23209295). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (PubMed:20418806, PubMed:23209295). Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (PubMed:20418806, PubMed:23209295). {ECO:0000250|UniProtKB:P60519, ECO:0000269|PubMed:20418806, ECO:0000269|PubMed:23209295}. |
| Q8IWW6 | ARHGAP12 | S656 | Sugiyama | Rho GTPase-activating protein 12 (Rho-type GTPase-activating protein 12) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}. |
| Q96KB5 | PBK | S110 | Sugiyama | Lymphokine-activated killer T-cell-originated protein kinase (EC 2.7.12.2) (Cancer/testis antigen 84) (CT84) (MAPKK-like protein kinase) (Nori-3) (PDZ-binding kinase) (Spermatogenesis-related protein kinase) (SPK) (T-LAK cell-originated protein kinase) | Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage. {ECO:0000269|PubMed:10781613, ECO:0000269|PubMed:17482142}. |
| Q9UHD2 | TBK1 | S531 | Sugiyama | Serine/threonine-protein kinase TBK1 (EC 2.7.11.1) (NF-kappa-B-activating kinase) (T2K) (TANK-binding kinase 1) | Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:11839743, PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:15485837, PubMed:18583960, PubMed:21138416, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:25636800, PubMed:26611359, PubMed:32404352, PubMed:34363755, PubMed:32298923). Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X (PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:18583960, PubMed:25636800). This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB (PubMed:12702806, PubMed:15367631, PubMed:25636800, PubMed:32972995). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:23453971, PubMed:23453972, PubMed:23746807). Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800, PubMed:30842653, PubMed:37926288). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (PubMed:21931631). Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus (PubMed:10783893, PubMed:15489227). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (PubMed:31709703). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, which leads to a negative impact on insulin sensitivity (By similarity). Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system (PubMed:22851595). Acts both as a positive and negative regulator of the mTORC1 complex, depending on the context: activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR, while it limits the mTORC1 complex by promoting phosphorylation of RPTOR (PubMed:29150432, PubMed:31530866). Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR, leading to increased phosphorylation and activation of AKT1 (By similarity). Phosphorylates and activates AKT1 (PubMed:21464307). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (PubMed:34363755). Also participates in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed:27135603). {ECO:0000250|UniProtKB:Q9WUN2, ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:12692549, ECO:0000269|PubMed:12702806, ECO:0000269|PubMed:14703513, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:15489227, ECO:0000269|PubMed:16155125, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21270402, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:22851595, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:23746807, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:26611359, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27135603, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:31530866, ECO:0000269|PubMed:31709703, ECO:0000269|PubMed:32298923, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:34363755, ECO:0000269|PubMed:37926288}. |
| Q8WVK2 | SNRNP27 | S123 | Sugiyama | U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein (U4/U6.U5 snRNP 27 kDa protein) (U4/U6.U5-27K) (Nucleic acid-binding protein RY-1) (U4/U6.U5 tri-snRNP-associated 27 kDa protein) (27K) (U4/U6.U5 tri-snRNP-associated protein 3) | May play a role in mRNA splicing. |
| A0A0B4J1R7 | BORCS7-ASMT | S43 | ochoa | BLOC-1-related complex subunit 7 | None |
| A0A0C4DFX4 | None | S549 | ochoa | Snf2 related CREBBP activator protein | None |
| A0FGR8 | ESYT2 | S699 | ochoa | Extended synaptotagmin-2 (E-Syt2) (Chr2Syt) | Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}. |
| A0JNW5 | BLTP3B | S989 | ochoa | Bridge-like lipid transfer protein family member 3B (Syntaxin-6 Habc-interacting protein of 164 kDa) (UHRF1-binding protein 1-like) | Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:20163565, PubMed:35499567). {ECO:0000269|PubMed:20163565, ECO:0000269|PubMed:35499567}. |
| A1L170 | C1orf226 | S30 | ochoa | Uncharacterized protein C1orf226 | None |
| A1L170 | C1orf226 | S35 | ochoa | Uncharacterized protein C1orf226 | None |
| A1L390 | PLEKHG3 | S827 | ochoa | Pleckstrin homology domain-containing family G member 3 (PH domain-containing family G member 3) | Plays a role in controlling cell polarity and cell motility by selectively binding newly polymerized actin and activating RAC1 and CDC42 to enhance local actin polymerization. {ECO:0000269|PubMed:27555588}. |
| A3KN83 | SBNO1 | S904 | ochoa | Protein strawberry notch homolog 1 (Monocyte protein 3) (MOP-3) | Plays a crucial role in the regulation of neural stem cells (NSCs) proliferation. Enhances the phosphorylation of GSK3B through the PI3K-Akt signaling pathway, thereby upregulating the Wnt/beta-catenin signaling pathway and promoting the proliferation of NSCs. Improves ischemic stroke recovery while inhibiting neuroinflammation through small extracellular vesicles (sEVs)-mediated mechanism. Enhances the secretion of sEVs from NSCs, which in turn inhibit both the MAPK and NF-kappaB pathways in microglia. This inhibition suppresses the pro-inflammatory M1 polarization of microglia, promoting a shift towards the M2 anti-inflammatory phenotype, which is beneficial for reducing neuroinflammation. {ECO:0000250|UniProtKB:Q689Z5}. |
| A4D2B0 | MBLAC1 | S65 | ochoa | Metallo-beta-lactamase domain-containing protein 1 (EC 3.1.27.-) (Endoribonuclease MBLAC1) | Endoribonuclease that catalyzes the hydrolysis of histone-coding pre-mRNA 3'-end. Involved in histone pre-mRNA processing during the S-phase of the cell cycle, which is required for entering/progressing through S-phase (PubMed:30507380). Cleaves histone pre-mRNA at a major and a minor cleavage site after the 5'-ACCCA-3' and the 5'-ACCCACA-3' sequence, respectively, and located downstream of the stem-loop (PubMed:30507380). May require the presence of the HDE element located at the histone pre-RNA 3'-end to avoid non-specific cleavage (PubMed:30507380). {ECO:0000269|PubMed:30507380}. |
| A4D2H0 | CTAGE15 | S656 | ochoa | cTAGE family member 15 (Protein cTAGE-15) | None |
| A4UGR9 | XIRP2 | S2643 | ochoa | Xin actin-binding repeat-containing protein 2 (Beta-xin) (Cardiomyopathy-associated protein 3) (Xeplin) | Protects actin filaments from depolymerization (PubMed:15454575). Required for correct morphology of cell membranes and maturation of intercalated disks of cardiomyocytes via facilitating localization of XIRP1 and CDH2 to the termini of aligned mature cardiomyocytes (By similarity). Thereby required for correct postnatal heart development and growth regulation that is crucial for overall heart morphology and diastolic function (By similarity). Required for normal electrical conduction in the heart including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with the cardiac ion channel components Scn5a/Nav1.5 and Kcna5/Kv1.5 (By similarity). Required for regular actin filament spacing of the paracrystalline array in both inner and outer hair cells of the cochlea, thereby required for maintenance of stereocilia morphology (By similarity). {ECO:0000250|UniProtKB:Q4U4S6, ECO:0000269|PubMed:15454575}. |
| A5YKK6 | CNOT1 | S1008 | ochoa | CCR4-NOT transcription complex subunit 1 (CCR4-associated factor 1) (Negative regulator of transcription subunit 1 homolog) (NOT1H) (hNOT1) | Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity. Plays a role in rapid sperm motility via mediating timely mRNA turnover (By similarity). {ECO:0000250|UniProtKB:Q6ZQ08, ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:32354837}. |
| A5YKK6 | CNOT1 | S1014 | ochoa | CCR4-NOT transcription complex subunit 1 (CCR4-associated factor 1) (Negative regulator of transcription subunit 1 homolog) (NOT1H) (hNOT1) | Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity. Plays a role in rapid sperm motility via mediating timely mRNA turnover (By similarity). {ECO:0000250|UniProtKB:Q6ZQ08, ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:32354837}. |
| A6ND36 | FAM83G | S666 | ochoa | Protein FAM83G (Protein associated with SMAD1) | Substrate for type I BMP receptor kinase involved in regulation of some target genes of the BMP signaling pathway. Also regulates the expression of several non-BMP target genes, suggesting a role in other signaling pathways. {ECO:0000269|PubMed:24554596}. |
| A6NDB9 | PALM3 | S284 | ochoa | Paralemmin-3 | ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling. {ECO:0000269|PubMed:21187075}. |
| A6NEQ0 | RBMY1E | S473 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member E | RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis. |
| A6NI28 | ARHGAP42 | S797 | ochoa | Rho GTPase-activating protein 42 (Rho GTPase-activating protein 10-like) (Rho-type GTPase-activating protein 42) | May influence blood pressure by functioning as a GTPase-activating protein for RHOA in vascular smooth muscle. {ECO:0000269|PubMed:24335996}. |
| A6NIX2 | WTIP | S96 | ochoa | Wilms tumor protein 1-interacting protein (WT1-interacting protein) | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates Hippo signaling pathway and antagonizes phosphorylation of YAP1. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. In podocytes, may play a role in the regulation of actin dynamics and/or foot process cytoarchitecture (By similarity). In the course of podocyte injury, shuttles into the nucleus and acts as a transcription regulator that represses WT1-dependent transcription regulation, thereby translating changes in slit diaphragm structure into altered gene expression and a less differentiated phenotype. Involved in the organization of the basal body (By similarity). Involved in cilia growth and positioning (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:A9LS46, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| A7XYQ1 | SOBP | S629 | ochoa | Sine oculis-binding protein homolog (Jackson circler protein 1) | Implicated in development of the cochlea. {ECO:0000250|UniProtKB:Q0P5V2}. |
| A8CG34 | POM121C | S325 | ochoa | Nuclear envelope pore membrane protein POM 121C (Nuclear pore membrane protein 121-2) (POM121-2) (Pore membrane protein of 121 kDa C) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| A8MV72 | None | S204 | ochoa | Putative UPF0607 protein ENSP00000382826 | None |
| C9JH25 | PRRT4 | S533 | ochoa | Proline-rich transmembrane protein 4 | None |
| C9JVG2 | ZNF775 | S71 | ochoa | Zinc finger protein 775 | None |
| H0YC42 | None | S159 | ochoa | Tumor protein D52 | None |
| K7ENP7 | None | S32 | ochoa | INO80 complex subunit C | None |
| K7EQG2 | None | S49 | ochoa | Uncharacterized protein | None |
| K7EQG2 | None | S133 | ochoa | Uncharacterized protein | None |
| M0QYT0 | None | S206 | ochoa | RRM domain-containing protein | None |
| M0QZ92 | None | S40 | ochoa | SEC7 domain-containing protein | None |
| O00139 | KIF2A | S135 | ochoa|psp | Kinesin-like protein KIF2A (Kinesin-2) (hK2) | Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity. {ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:30785839}. |
| O00192 | ARVCF | S606 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00193 | SMAP | S24 | ochoa | Small acidic protein | None |
| O00267 | SUPT5H | S158 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00267 | SUPT5H | S780 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00267 | SUPT5H | S789 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00267 | SUPT5H | S797 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00267 | SUPT5H | S812 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00268 | TAF4 | S1027 | ochoa | Transcription initiation factor TFIID subunit 4 (RNA polymerase II TBP-associated factor subunit C) (TBP-associated factor 4) (Transcription initiation factor TFIID 130 kDa subunit) (TAF(II)130) (TAFII-130) (TAFII130) (Transcription initiation factor TFIID 135 kDa subunit) (TAF(II)135) (TAFII-135) (TAFII135) | The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:10594036, PubMed:33795473, PubMed:8942982). TAF4 may maintain an association between the TFIID and TFIIA complexes, while bound to the promoter, together with TBP, during PIC assembly (PubMed:33795473). Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone (PubMed:9192867). {ECO:0000269|PubMed:10594036, ECO:0000269|PubMed:33795473, ECO:0000269|PubMed:8942982, ECO:0000269|PubMed:9192867}. |
| O00425 | IGF2BP3 | S179 | ochoa | Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2 mRNA-binding protein 3) (IMP-3) (IGF-II mRNA-binding protein 3) (KH domain-containing protein overexpressed in cancer) (hKOC) (VICKZ family member 3) | RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (PubMed:29476152). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (PubMed:29476152). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. {ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:23640942, ECO:0000269|PubMed:29476152}. |
| O00458 | IFRD1 | S21 | ochoa | Interferon-related developmental regulator 1 (Nerve growth factor-inducible protein PC4) | Could play a role in regulating gene activity in the proliferative and/or differentiative pathways induced by NGF. May be an autocrine factor that attenuates or amplifies the initial ligand-induced signal (By similarity). {ECO:0000250}. |
| O00512 | BCL9 | S321 | ochoa | B-cell CLL/lymphoma 9 protein (B-cell lymphoma 9 protein) (Bcl-9) (Protein legless homolog) | Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:11955446}. |
| O00567 | NOP56 | S528 | ochoa | Nucleolar protein 56 (Nucleolar protein 5A) | Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs (PubMed:12777385, PubMed:15574333). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:12777385, PubMed:39570315). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| O14490 | DLGAP1 | S346 | psp | Disks large-associated protein 1 (DAP-1) (Guanylate kinase-associated protein) (hGKAP) (PSD-95/SAP90-binding protein 1) (SAP90/PSD-95-associated protein 1) (SAPAP1) | Part of the postsynaptic scaffold in neuronal cells. |
| O14497 | ARID1A | S610 | ochoa | AT-rich interactive domain-containing protein 1A (ARID domain-containing protein 1A) (B120) (BRG1-associated factor 250) (BAF250) (BRG1-associated factor 250a) (BAF250A) (Osa homolog 1) (hOSA1) (SWI-like protein) (SWI/SNF complex protein p270) (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1) (hELD) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:A2BH40, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| O14523 | C2CD2L | S623 | ochoa | Phospholipid transfer protein C2CD2L (C2 domain-containing protein 2-like) (C2CD2-like) (Transmembrane protein 24) | Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}. |
| O14640 | DVL1 | S600 | ochoa | Segment polarity protein dishevelled homolog DVL-1 (Dishevelled-1) (DSH homolog 1) | Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). |
| O14640 | DVL1 | S602 | ochoa | Segment polarity protein dishevelled homolog DVL-1 (Dishevelled-1) (DSH homolog 1) | Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). |
| O14641 | DVL2 | S618 | psp | Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) | Plays a role in the signal transduction pathways mediated by multiple Wnt genes (PubMed:24616100). Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499, ECO:0000269|PubMed:24616100}. |
| O14641 | DVL2 | S620 | ochoa | Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) | Plays a role in the signal transduction pathways mediated by multiple Wnt genes (PubMed:24616100). Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499, ECO:0000269|PubMed:24616100}. |
| O14646 | CHD1 | S1085 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O14654 | IRS4 | S463 | ochoa | Insulin receptor substrate 4 (IRS-4) (160 kDa phosphotyrosine protein) (py160) (Phosphoprotein of 160 kDa) (pp160) | Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2. {ECO:0000269|PubMed:10531310, ECO:0000269|PubMed:10594015, ECO:0000269|PubMed:12639902, ECO:0000269|PubMed:17408801, ECO:0000269|PubMed:9553137}. |
| O14654 | IRS4 | S465 | ochoa | Insulin receptor substrate 4 (IRS-4) (160 kDa phosphotyrosine protein) (py160) (Phosphoprotein of 160 kDa) (pp160) | Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2. {ECO:0000269|PubMed:10531310, ECO:0000269|PubMed:10594015, ECO:0000269|PubMed:12639902, ECO:0000269|PubMed:17408801, ECO:0000269|PubMed:9553137}. |
| O14654 | IRS4 | S863 | ochoa | Insulin receptor substrate 4 (IRS-4) (160 kDa phosphotyrosine protein) (py160) (Phosphoprotein of 160 kDa) (pp160) | Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2. {ECO:0000269|PubMed:10531310, ECO:0000269|PubMed:10594015, ECO:0000269|PubMed:12639902, ECO:0000269|PubMed:17408801, ECO:0000269|PubMed:9553137}. |
| O14686 | KMT2D | S2654 | ochoa | Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}. |
| O14715 | RGPD8 | S1223 | ochoa | RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) | None |
| O14908 | GIPC1 | S232 | ochoa | PDZ domain-containing protein GIPC1 (GAIP C-terminus-interacting protein) (RGS-GAIP-interacting protein) (RGS19-interacting protein 1) (Synectin) (Tax interaction protein 2) (TIP-2) | May be involved in G protein-linked signaling. |
| O14920 | IKBKB | S177 | psp | Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK-2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:9346484}. |
| O14974 | PPP1R12A | S877 | ochoa | Protein phosphatase 1 regulatory subunit 12A (Myosin phosphatase-targeting subunit 1) (Myosin phosphatase target subunit 1) (Protein phosphatase myosin-binding subunit) | Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity. {ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:20354225}. |
| O15020 | SPTBN2 | S2171 | ochoa | Spectrin beta chain, non-erythrocytic 2 (Beta-III spectrin) (Spinocerebellar ataxia 5 protein) | Probably plays an important role in neuronal membrane skeleton. |
| O15027 | SEC16A | S561 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15047 | SETD1A | S528 | ochoa | Histone-lysine N-methyltransferase SETD1A (EC 2.1.1.364) (Lysine N-methyltransferase 2F) (SET domain-containing protein 1A) (hSET1A) (Set1/Ash2 histone methyltransferase complex subunit SET1) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism (PubMed:12670868, PubMed:25561738). Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:29937342, PubMed:31197650, PubMed:32346159). Responsible for H3K4me3 enriched promoters and transcriptional programming of inner mass stem cells and neuron progenitors during embryogenesis (By similarity) (PubMed:31197650). Required for H3K4me1 mark at stalled replication forks. Mediates FANCD2-dependent nucleosome remodeling and RAD51 nucleofilaments stabilization at reversed forks, protecting them from nucleolytic degradation (PubMed:29937342, PubMed:32346159). Does not methylate 'Lys-4' of histone H3 if the neighboring 'Lys-9' residue is already methylated (PubMed:12670868). Binds RNAs involved in RNA processing and the DNA damage response (PubMed:38003223). {ECO:0000250|UniProtKB:E9PYH6, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:29937342, ECO:0000269|PubMed:31197650, ECO:0000269|PubMed:32346159, ECO:0000269|PubMed:38003223}. |
| O15047 | SETD1A | S534 | ochoa | Histone-lysine N-methyltransferase SETD1A (EC 2.1.1.364) (Lysine N-methyltransferase 2F) (SET domain-containing protein 1A) (hSET1A) (Set1/Ash2 histone methyltransferase complex subunit SET1) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism (PubMed:12670868, PubMed:25561738). Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:29937342, PubMed:31197650, PubMed:32346159). Responsible for H3K4me3 enriched promoters and transcriptional programming of inner mass stem cells and neuron progenitors during embryogenesis (By similarity) (PubMed:31197650). Required for H3K4me1 mark at stalled replication forks. Mediates FANCD2-dependent nucleosome remodeling and RAD51 nucleofilaments stabilization at reversed forks, protecting them from nucleolytic degradation (PubMed:29937342, PubMed:32346159). Does not methylate 'Lys-4' of histone H3 if the neighboring 'Lys-9' residue is already methylated (PubMed:12670868). Binds RNAs involved in RNA processing and the DNA damage response (PubMed:38003223). {ECO:0000250|UniProtKB:E9PYH6, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:29937342, ECO:0000269|PubMed:31197650, ECO:0000269|PubMed:32346159, ECO:0000269|PubMed:38003223}. |
| O15061 | SYNM | S384 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15063 | GARRE1 | S210 | ochoa | Granule associated Rac and RHOG effector protein 1 (GARRE1) | Acts as an effector of RAC1 (PubMed:31871319). Associates with CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation (PubMed:29395067). May also play a role in miRNA silencing machinery (PubMed:29395067). {ECO:0000269|PubMed:29395067, ECO:0000269|PubMed:31871319}. |
| O15068 | MCF2L | S589 | ochoa | Guanine nucleotide exchange factor DBS (DBL's big sister) (MCF2-transforming sequence-like protein) | Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways (By similarity). Seems to lack activity with RAC1. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). Isoform 5 activates CDC42 (PubMed:15157669). {ECO:0000250|UniProtKB:Q63406, ECO:0000269|PubMed:15157669}.; FUNCTION: [Isoform 3]: Does not catalyze guanine nucleotide exchange on CDC42 (PubMed:15157669). {ECO:0000269|PubMed:15157669}. |
| O15085 | ARHGEF11 | S271 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15085 | ARHGEF11 | S1135 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15209 | ZBTB22 | S599 | ochoa | Zinc finger and BTB domain-containing protein 22 (Protein BING1) (Zinc finger and BTB domain-containing protein 22A) (Zinc finger protein 297) | May be involved in transcriptional regulation. |
| O15234 | CASC3 | S23 | ochoa | Protein CASC3 (Cancer susceptibility candidate gene 3 protein) (Metastatic lymph node gene 51 protein) (MLN 51) (Protein barentsz) (Btz) | Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homomer. {ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:17652158, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}. |
| O15327 | INPP4B | S549 | ochoa | Inositol polyphosphate 4-phosphatase type II (Type II inositol 3,4-bisphosphate 4-phosphatase) (EC 3.1.3.66) | Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-trisphosphate (PubMed:24070612, PubMed:24591580). Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles (PubMed:24591580). The lipid phosphatase activity is critical for tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:19647222, PubMed:24070612). {ECO:0000269|PubMed:19647222, ECO:0000269|PubMed:24070612, ECO:0000269|PubMed:24591580}. |
| O15355 | PPM1G | S325 | ochoa | Protein phosphatase 1G (EC 3.1.3.16) (Protein phosphatase 1C) (Protein phosphatase 2C isoform gamma) (PP2C-gamma) (Protein phosphatase magnesium-dependent 1 gamma) | None |
| O15511 | ARPC5 | S77 | psp | Actin-related protein 2/3 complex subunit 5 (Arp2/3 complex 16 kDa subunit) (p16-ARC) | Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}. |
| O15516 | CLOCK | S408 | ochoa | Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 8) (bHLHe8) | Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). {ECO:0000250|UniProtKB:O08785, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}. |
| O15530 | PDPK1 | S64 | ochoa|psp | 3-phosphoinositide-dependent protein kinase 1 (hPDK1) (EC 2.7.11.1) | Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9445477, PubMed:9707564, PubMed:9768361). Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), TSSK3, protein kinase PKN (PKN1 and PKN2) (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9707564, PubMed:9768361). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage (PubMed:10226025, PubMed:12167717, PubMed:9094314). Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta (PubMed:17327236). Activates PPARG transcriptional activity and promotes adipocyte differentiation (By similarity). Activates the NF-kappa-B pathway via phosphorylation of IKKB (PubMed:16207722). The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II (PubMed:14585963). Controls proliferation, survival, and growth of developing pancreatic cells (By similarity). Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells (By similarity). Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis (PubMed:17371830). Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response (By similarity). Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses (By similarity). Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages (By similarity). {ECO:0000250|UniProtKB:Q9Z2A0, ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9368760, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9445477, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.; FUNCTION: [Isoform 3]: Catalytically inactive. {ECO:0000269|PubMed:9445477}. |
| O15534 | PER1 | S601 | ochoa | Period circadian protein homolog 1 (hPER1) (Circadian clock protein PERIOD 1) (Circadian pacemaker protein Rigui) | Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by BMAL1:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:24005054}. |
| O43159 | RRP8 | S124 | ochoa | Ribosomal RNA-processing protein 8 (EC 2.1.1.-) (Cerebral protein 1) (Nucleomethylin) | Essential component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the complex, RRP8 binds to H3K9me2 and probably acts as a methyltransferase. Its substrates are however unknown. {ECO:0000269|PubMed:18485871}. |
| O43182 | ARHGAP6 | S754 | ochoa | Rho GTPase-activating protein 6 (Rho-type GTPase-activating protein 6) (Rho-type GTPase-activating protein RhoGAPX-1) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Could regulate the interactions of signaling molecules with the actin cytoskeleton. Promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. {ECO:0000269|PubMed:10699171}. |
| O43242 | PSMD3 | S47 | ochoa | 26S proteasome non-ATPase regulatory subunit 3 (26S proteasome regulatory subunit RPN3) (26S proteasome regulatory subunit S3) (Proteasome subunit p58) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}. |
| O43294 | TGFB1I1 | S46 | ochoa | Transforming growth factor beta-1-induced transcript 1 protein (Androgen receptor coactivator 55 kDa protein) (Androgen receptor-associated protein of 55 kDa) (Hydrogen peroxide-inducible clone 5 protein) (Hic-5) | Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity. {ECO:0000269|PubMed:10075738, ECO:0000269|PubMed:11463817, ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12445807, ECO:0000269|PubMed:12700349, ECO:0000269|PubMed:15211577, ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:16141357, ECO:0000269|PubMed:16624805, ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536, ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9032249}. |
| O43314 | PPIP5K2 | S646 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}. |
| O43390 | HNRNPR | S252 | ochoa | Heterogeneous nuclear ribonucleoprotein R (hnRNP R) | Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus. |
| O43491 | EPB41L2 | S47 | ochoa | Band 4.1-like protein 2 (Erythrocyte membrane protein band 4.1-like 2) (Generally expressed protein 4.1) (4.1G) | Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}. |
| O43491 | EPB41L2 | S718 | ochoa | Band 4.1-like protein 2 (Erythrocyte membrane protein band 4.1-like 2) (Generally expressed protein 4.1) (4.1G) | Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}. |
| O43493 | TGOLN2 | S221 | ochoa | Trans-Golgi network integral membrane protein 2 (Trans-Golgi network glycoprotein 46) (TGN38 homolog) (hTGN46) (Trans-Golgi network glycoprotein 48) (hTGN48) (Trans-Golgi network glycoprotein 51) (hTGN51) (Trans-Golgi network protein 2) | May be involved in regulating membrane traffic to and from trans-Golgi network. |
| O43524 | FOXO3 | S75 | ochoa | Forkhead box protein O3 (AF6q21 protein) (Forkhead in rhabdomyosarcoma-like 1) | Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882, PubMed:30513302). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (PubMed:30513302). {ECO:0000250|UniProtKB:Q9WVH4, ECO:0000269|PubMed:10102273, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:30513302}. |
| O43561 | LAT | S91 | ochoa | Linker for activation of T-cells family member 1 (36 kDa phosphotyrosine adapter protein) (pp36) (p36-38) | Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. {ECO:0000269|PubMed:10072481, ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:25907557}. |
| O43566 | RGS14 | S198 | ochoa | Regulator of G-protein signaling 14 (RGS14) | Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o)-alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory. {ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:17635935}. |
| O43566 | RGS14 | S291 | ochoa | Regulator of G-protein signaling 14 (RGS14) | Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o)-alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory. {ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:17635935}. |
| O43572 | AKAP10 | S540 | ochoa | A-kinase anchor protein 10, mitochondrial (AKAP-10) (Dual specificity A kinase-anchoring protein 2) (D-AKAP-2) (Protein kinase A-anchoring protein 10) (PRKA10) | Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase (By similarity). {ECO:0000250}. |
| O43663 | PRC1 | S267 | ochoa | Protein regulator of cytokinesis 1 | Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}. |
| O43663 | PRC1 | S466 | ochoa | Protein regulator of cytokinesis 1 | Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}. |
| O43683 | BUB1 | S331 | ochoa|psp | Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) | Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}. |
| O43707 | ACTN4 | S608 | ochoa | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| O43823 | AKAP8 | S112 | ochoa | A-kinase anchor protein 8 (AKAP-8) (A-kinase anchor protein 95 kDa) (AKAP 95) | Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II) (PubMed:9473338). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (PubMed:10601332, PubMed:10791967, PubMed:11964380). May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794). May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381). Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation (PubMed:23995757). May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274). May play a repressive role in the regulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and transcribed regions (PubMed:26683827). Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (By similarity). {ECO:0000250|UniProtKB:Q63014, ECO:0000250|UniProtKB:Q9DBR0, ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:10791967, ECO:0000269|PubMed:11964380, ECO:0000269|PubMed:16980585, ECO:0000269|PubMed:22130794, ECO:0000269|PubMed:26683827, ECO:0000269|PubMed:26880274, ECO:0000305|PubMed:14641107, ECO:0000305|PubMed:9473338}. |
| O43823 | AKAP8 | S165 | ochoa | A-kinase anchor protein 8 (AKAP-8) (A-kinase anchor protein 95 kDa) (AKAP 95) | Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II) (PubMed:9473338). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (PubMed:10601332, PubMed:10791967, PubMed:11964380). May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794). May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381). Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation (PubMed:23995757). May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274). May play a repressive role in the regulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and transcribed regions (PubMed:26683827). Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (By similarity). {ECO:0000250|UniProtKB:Q63014, ECO:0000250|UniProtKB:Q9DBR0, ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:10791967, ECO:0000269|PubMed:11964380, ECO:0000269|PubMed:16980585, ECO:0000269|PubMed:22130794, ECO:0000269|PubMed:26683827, ECO:0000269|PubMed:26880274, ECO:0000305|PubMed:14641107, ECO:0000305|PubMed:9473338}. |
| O43829 | ZBTB14 | S233 | ochoa | Zinc finger and BTB domain-containing protein 14 (Zinc finger protein 161 homolog) (Zfp-161) (Zinc finger protein 478) (Zinc finger protein 5 homolog) (ZF5) (Zfp-5) (hZF5) | Transcriptional activator of the dopamine transporter (DAT), binding it's promoter at the consensus sequence 5'-CCTGCACAGTTCACGGA-3'. Binds to 5'-d(GCC)(n)-3' trinucleotide repeats in promoter regions and acts as a repressor of the FMR1 gene. Transcriptional repressor of MYC and thymidine kinase promoters. {ECO:0000269|PubMed:17714511}. |
| O43829 | ZBTB14 | S393 | ochoa | Zinc finger and BTB domain-containing protein 14 (Zinc finger protein 161 homolog) (Zfp-161) (Zinc finger protein 478) (Zinc finger protein 5 homolog) (ZF5) (Zfp-5) (hZF5) | Transcriptional activator of the dopamine transporter (DAT), binding it's promoter at the consensus sequence 5'-CCTGCACAGTTCACGGA-3'. Binds to 5'-d(GCC)(n)-3' trinucleotide repeats in promoter regions and acts as a repressor of the FMR1 gene. Transcriptional repressor of MYC and thymidine kinase promoters. {ECO:0000269|PubMed:17714511}. |
| O43847 | NRDC | S94 | ochoa | Nardilysin (EC 3.4.24.61) (N-arginine dibasic convertase) (NRD convertase) (NRD-C) (Nardilysin convertase) | Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs. Is a critical activator of BACE1- and ADAM17-mediated pro-neuregulin ectodomain shedding, involved in the positive regulation of axonal maturation and myelination. Required for proper functioning of 2-oxoglutarate dehydrogenase (OGDH) (By similarity). {ECO:0000250|UniProtKB:Q8BHG1}. |
| O43896 | KIF1C | S817 | ochoa | Kinesin-like protein KIF1C | Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:9685376}. |
| O60237 | PPP1R12B | S842 | ochoa | Protein phosphatase 1 regulatory subunit 12B (Myosin phosphatase-targeting subunit 2) (Myosin phosphatase target subunit 2) | Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus. {ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:9570949}. |
| O60271 | SPAG9 | S272 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60271 | SPAG9 | S391 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60279 | SUSD5 | S105 | ochoa | Sushi domain-containing protein 5 | None |
| O60341 | KDM1A | S93 | ochoa | Lysine-specific histone demethylase 1A (EC 1.14.99.66) (BRAF35-HDAC complex protein BHC110) (Flavin-containing amine oxidase domain-containing protein 2) ([histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A) | Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:16079795, PubMed:16140033, PubMed:16223729, PubMed:27292636). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16079794, PubMed:16140033). Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636). Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). Required for the repression of GIPR expression (PubMed:34655521, PubMed:34906447). {ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:15620353, ECO:0000269|PubMed:15811342, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:16140033, ECO:0000269|PubMed:16223729, ECO:0000269|PubMed:16885027, ECO:0000269|PubMed:16956976, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:23721412, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:29358331, ECO:0000269|PubMed:29691401, ECO:0000269|PubMed:34655521, ECO:0000269|PubMed:34906447}. |
| O60447 | EVI5 | S765 | ochoa | Ecotropic viral integration site 5 protein homolog (EVI-5) (Neuroblastoma stage 4S gene protein) | Functions as a regulator of cell cycle progression by stabilizing the FBXO5 protein and promoting cyclin-A accumulation during interphase. May play a role in cytokinesis. {ECO:0000269|PubMed:16439210}. |
| O60506 | SYNCRIP | S249 | ochoa | Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) (Glycine- and tyrosine-rich RNA-binding protein) (GRY-RBP) (NS1-associated protein 1) (Synaptotagmin-binding, cytoplasmic RNA-interacting protein) | Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; seems not to be essential for GAIT complex function. {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:11134005, ECO:0000269|PubMed:11352648, ECO:0000269|PubMed:11574476, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:23071094}. |
| O60658 | PDE8A | S59 | ochoa | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC 3.1.4.53) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299). {ECO:0000269|PubMed:18983167, ECO:0000269|PubMed:23509299}. |
| O60884 | DNAJA2 | S78 | ochoa | DnaJ homolog subfamily A member 2 (Cell cycle progression restoration gene 3 protein) (Dnj3) (Dj3) (HIRA-interacting protein 4) (Renal carcinoma antigen NY-REN-14) | Co-chaperone of Hsc70. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro) (PubMed:24318877). {ECO:0000269|PubMed:24318877}. |
| O60884 | DNAJA2 | S382 | ochoa | DnaJ homolog subfamily A member 2 (Cell cycle progression restoration gene 3 protein) (Dnj3) (Dj3) (HIRA-interacting protein 4) (Renal carcinoma antigen NY-REN-14) | Co-chaperone of Hsc70. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro) (PubMed:24318877). {ECO:0000269|PubMed:24318877}. |
| O75061 | DNAJC6 | S662 | ochoa | Auxilin (EC 3.1.3.-) (DnaJ homolog subfamily C member 6) | May act as a protein phosphatase and/or a lipid phosphatase. Co-chaperone that recruits HSPA8/HSC70 to clathrin-coated vesicles (CCVs) and promotes the ATP-dependent dissociation of clathrin from CCVs and participates in clathrin-mediated endocytosis of synaptic vesicles and their recycling and also in intracellular trafficking (PubMed:18489706). Firstly, binds tightly to the clathrin cages, at a ratio of one DNAJC6 per clathrin triskelion. The HSPA8:ATP complex then binds to the clathrin-auxilin cage, initially at a ratio of one HSPA8 per triskelion leading to ATP hydrolysis stimulation and causing a conformational change in the HSPA8. This cycle is repeated three times to drive to a complex containing the clathrin-auxilin cage associated to three HSPA8:ADP complex. The ATP hydrolysis of the third HSPA8:ATP complex leads to a concerted dismantling of the cage into component triskelia. Then, dissociates from the released triskelia and be recycled to initiate another cycle of HSPA8's recruitment. Also acts during the early steps of clathrin-coated vesicle (CCV) formation through its interaction with the GTP bound form of DNM1 (By similarity). {ECO:0000250|UniProtKB:Q27974, ECO:0000269|PubMed:18489706}. |
| O75069 | TMCC2 | S438 | ochoa | Transmembrane and coiled-coil domains protein 2 (Cerebral protein 11) | May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE. {ECO:0000269|PubMed:21593558}. |
| O75069 | TMCC2 | S464 | ochoa | Transmembrane and coiled-coil domains protein 2 (Cerebral protein 11) | May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE. {ECO:0000269|PubMed:21593558}. |
| O75069 | TMCC2 | S491 | ochoa | Transmembrane and coiled-coil domains protein 2 (Cerebral protein 11) | May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE. {ECO:0000269|PubMed:21593558}. |
| O75146 | HIP1R | S1017 | ochoa | Huntingtin-interacting protein 1-related protein (HIP1-related protein) (Huntingtin-interacting protein 12) (HIP-12) | Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. {ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:14732715}. |
| O75150 | RNF40 | S525 | ochoa | E3 ubiquitin-protein ligase BRE1B (BRE1-B) (EC 2.3.2.27) (95 kDa retinoblastoma-associated protein) (RBP95) (RING finger protein 40) (RING-type E3 ubiquitin transferase BRE1B) | Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively). It thereby plays a central role in histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes. {ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19410543}.; FUNCTION: (Microbial infection) Promotes the human herpesvirus 8 (KSHV) lytic cycle by inducing the expression of lytic viral genes including the latency switch gene RTA/ORF50. {ECO:0000269|PubMed:37888983}. |
| O75153 | CLUH | S669 | ochoa | Clustered mitochondria protein homolog | mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria. Specifically binds mRNAs of nuclear-encoded mitochondrial proteins in the cytoplasm and regulates transport or translation of these transcripts close to mitochondria, playing a role in mitochondrial biogenesis. {ECO:0000255|HAMAP-Rule:MF_03013, ECO:0000269|PubMed:25349259}. |
| O75334 | PPFIA2 | S260 | ochoa | Liprin-alpha-2 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-2) (PTPRF-interacting protein alpha-2) | Alters PTPRF cellular localization and induces PTPRF clustering. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. In neuronal cells, is a scaffolding protein in the dendritic spines which acts as immobile postsynaptic post able to recruit KIF1A-driven dense core vesicles to dendritic spines (PubMed:30021165). {ECO:0000269|PubMed:30021165, ECO:0000269|PubMed:9624153}. |
| O75348 | ATP6V1G1 | S65 | ochoa | V-type proton ATPase subunit G 1 (V-ATPase subunit G 1) (V-ATPase 13 kDa subunit 1) (Vacuolar proton pump subunit G 1) (Vacuolar proton pump subunit M16) | Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:32001091, PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). {ECO:0000269|PubMed:28296633, ECO:0000269|PubMed:33065002, ECO:0000303|PubMed:32001091}. |
| O75376 | NCOR1 | S1750 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75376 | NCOR1 | S1952 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75381 | PEX14 | S286 | ochoa | Peroxisomal membrane protein PEX14 (PTS1 receptor-docking protein) (Peroxin-14) (Peroxisomal membrane anchor protein PEX14) | Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (PubMed:24235149, PubMed:28765278, PubMed:9653144). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix (PubMed:24235149, PubMed:28765278). Plays a key role for peroxisome movement through a direct interaction with tubulin (PubMed:21525035). {ECO:0000250|UniProtKB:P53112, ECO:0000269|PubMed:21525035, ECO:0000269|PubMed:24235149, ECO:0000269|PubMed:28765278, ECO:0000269|PubMed:9653144}. |
| O75385 | ULK1 | S538 | ochoa | Serine/threonine-protein kinase ULK1 (EC 2.7.11.1) (Autophagy-related protein 1 homolog) (ATG1) (hATG1) (Unc-51-like kinase 1) | Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708). {ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:20921139, ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:37306101}. |
| O75385 | ULK1 | S781 | ochoa | Serine/threonine-protein kinase ULK1 (EC 2.7.11.1) (Autophagy-related protein 1 homolog) (ATG1) (hATG1) (Unc-51-like kinase 1) | Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708). {ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:20921139, ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:37306101}. |
| O75396 | SEC22B | S137 | ochoa | Vesicle-trafficking protein SEC22b (ER-Golgi SNARE of 24 kDa) (ERS-24) (ERS24) (SEC22 vesicle-trafficking protein homolog B) (SEC22 vesicle-trafficking protein-like 1) | SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER. {ECO:0000269|PubMed:15272311}. |
| O75420 | GIGYF1 | S411 | ochoa | GRB10-interacting GYF protein 1 (PERQ amino acid-rich with GYF domain-containing protein 1) | May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:12771153}. |
| O75427 | LRCH4 | S267 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 4 (Leucine-rich repeat neuronal protein 4) (Leucine-rich neuronal protein) | Accessory protein that regulates signaling by multiple TLRs, acting as a broad-spanning regulator of the innate immune response. In macrophages, binds LPS and promotes proper docking of LPS in lipid raft membrane. May be required for lipid raft maintenance. {ECO:0000250|UniProtKB:Q921G6}. |
| O75427 | LRCH4 | S346 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 4 (Leucine-rich repeat neuronal protein 4) (Leucine-rich neuronal protein) | Accessory protein that regulates signaling by multiple TLRs, acting as a broad-spanning regulator of the innate immune response. In macrophages, binds LPS and promotes proper docking of LPS in lipid raft membrane. May be required for lipid raft maintenance. {ECO:0000250|UniProtKB:Q921G6}. |
| O75533 | SF3B1 | S349 | ochoa | Splicing factor 3B subunit 1 (Pre-mRNA-splicing factor SF3b 155 kDa subunit) (SF3b155) (Spliceosome-associated protein 155) (SAP 155) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B1 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92 (By similarity). {ECO:0000250|UniProtKB:Q99NB9, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| O75604 | USP2 | S207 | ochoa|psp | Ubiquitin carboxyl-terminal hydrolase 2 (EC 3.4.19.12) (41 kDa ubiquitin-specific protease) (Deubiquitinating enzyme 2) (Ubiquitin thioesterase 2) (Ubiquitin-specific-processing protease 2) | Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19838211, PubMed:19917254). Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211). Has no deubiquitinase activity against p53/TP53 (PubMed:17290220). Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and BMAL1 (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity). {ECO:0000250|UniProtKB:O88623, ECO:0000250|UniProtKB:Q5U349, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:19917254}.; FUNCTION: [Isoform 4]: Circadian clock output effector that regulates Ca(2+) absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine. {ECO:0000250|UniProtKB:O88623}. |
| O75643 | SNRNP200 | S756 | ochoa | U5 small nuclear ribonucleoprotein 200 kDa helicase (EC 3.6.4.13) (Activating signal cointegrator 1 complex subunit 3-like 1) (BRR2 homolog) (U5 snRNP-specific 200 kDa protein) (U5-200KD) | Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome (PubMed:35241646). Plays a role in pre-mRNA splicing as a core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154, PubMed:30728453). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:23045696, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:35241646, ECO:0000269|PubMed:8670905, ECO:0000269|PubMed:9539711, ECO:0000305|PubMed:33509932}. |
| O75792 | RNASEH2A | S208 | psp | Ribonuclease H2 subunit A (RNase H2 subunit A) (EC 3.1.26.4) (Aicardi-Goutieres syndrome 4 protein) (AGS4) (RNase H(35)) (Ribonuclease HI large subunit) (RNase HI large subunit) (Ribonuclease HI subunit A) | Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:21177858}. |
| O75955 | FLOT1 | S385 | ochoa | Flotillin-1 | May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. |
| O75962 | TRIO | S2499 | ochoa | Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein) | Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity). {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}. |
| O75970 | MPDZ | S224 | ochoa | Multiple PDZ domain protein (Multi-PDZ domain protein 1) | Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses (PubMed:11150294, PubMed:15312654). Promotes clustering of HT2RC at the cell surface (By similarity). {ECO:0000250|UniProtKB:O55164, ECO:0000269|PubMed:11150294, ECO:0000269|PubMed:15312654}. |
| O76094 | SRP72 | S630 | ochoa | Signal recognition particle subunit SRP72 (SRP72) (Signal recognition particle 72 kDa protein) | Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (PubMed:34020957). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER (PubMed:34020957). The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER (PubMed:34020957). Binds the signal recognition particle RNA (7SL RNA) in presence of SRP68 (PubMed:21073748, PubMed:27899666). Can bind 7SL RNA with low affinity (PubMed:21073748, PubMed:27899666). The SRP complex possibly participates in the elongation arrest function (By similarity). {ECO:0000250|UniProtKB:P38688, ECO:0000269|PubMed:21073748, ECO:0000269|PubMed:27899666, ECO:0000269|PubMed:34020957}. |
| O94762 | RECQL5 | S488 | ochoa | ATP-dependent DNA helicase Q5 (EC 5.6.2.4) (DNA 3'-5' helicase RecQ5) (DNA helicase, RecQ-like type 5) (RecQ5) (RecQ protein-like 5) | DNA helicase that plays an important role in DNA replication, transcription and repair (PubMed:20643585, PubMed:22973052, PubMed:28100692). Probably unwinds DNA in a 3'-5' direction (Probable) (PubMed:28100692). Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability (PubMed:20231364). Also associates with POLR1A and enforces the stability of ribosomal DNA arrays (PubMed:27502483). Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress (PubMed:22013166). Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis (PubMed:28575661). Required for efficient DNA repair, including repair of inter-strand cross-links (PubMed:23715498). Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination. A core helicase fragment (residues 11-609) binds preferentially to splayed duplex, looped and ssDNA (PubMed:28100692). {ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20643585, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22973052, ECO:0000269|PubMed:23715498, ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:27502483, ECO:0000269|PubMed:28100692, ECO:0000269|PubMed:28575661, ECO:0000305|PubMed:28100692}. |
| O94762 | RECQL5 | S491 | ochoa | ATP-dependent DNA helicase Q5 (EC 5.6.2.4) (DNA 3'-5' helicase RecQ5) (DNA helicase, RecQ-like type 5) (RecQ5) (RecQ protein-like 5) | DNA helicase that plays an important role in DNA replication, transcription and repair (PubMed:20643585, PubMed:22973052, PubMed:28100692). Probably unwinds DNA in a 3'-5' direction (Probable) (PubMed:28100692). Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability (PubMed:20231364). Also associates with POLR1A and enforces the stability of ribosomal DNA arrays (PubMed:27502483). Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress (PubMed:22013166). Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis (PubMed:28575661). Required for efficient DNA repair, including repair of inter-strand cross-links (PubMed:23715498). Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination. A core helicase fragment (residues 11-609) binds preferentially to splayed duplex, looped and ssDNA (PubMed:28100692). {ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20643585, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22973052, ECO:0000269|PubMed:23715498, ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:27502483, ECO:0000269|PubMed:28100692, ECO:0000269|PubMed:28575661, ECO:0000305|PubMed:28100692}. |
| O94763 | URI1 | S375 | ochoa | Unconventional prefoldin RPB5 interactor 1 (Protein NNX3) (Protein phosphatase 1 regulatory subunit 19) (RNA polymerase II subunit 5-mediating protein) (RPB5-mediating protein) | Involved in gene transcription regulation. Acts as a transcriptional repressor in concert with the corepressor UXT to regulate androgen receptor (AR) transcription. May act as a tumor suppressor to repress AR-mediated gene transcription and to inhibit anchorage-independent growth in prostate cancer cells. Required for cell survival in ovarian cancer cells. Together with UXT, associates with chromatin to the NKX3-1 promoter region. Antagonizes transcriptional modulation via hepatitis B virus X protein.; FUNCTION: Plays a central role in maintaining S6K1 signaling and BAD phosphorylation under normal growth conditions thereby protecting cells from potential deleterious effects of sustained S6K1 signaling. The URI1-PPP1CC complex acts as a central component of a negative feedback mechanism that counteracts excessive S6K1 survival signaling to BAD in response to growth factors. Mediates inhibition of PPP1CC phosphatase activity in mitochondria. Coordinates the regulation of nutrient-sensitive gene expression availability in a mTOR-dependent manner. Seems to be a scaffolding protein able to assemble a prefoldin-like complex that contains PFDs and proteins with roles in transcription and ubiquitination. |
| O94819 | KBTBD11 | S82 | ochoa | Kelch repeat and BTB domain-containing protein 11 (Chronic myelogenous leukemia-associated protein) (Kelch domain-containing protein 7B) | None |
| O94819 | KBTBD11 | S510 | ochoa | Kelch repeat and BTB domain-containing protein 11 (Chronic myelogenous leukemia-associated protein) (Kelch domain-containing protein 7B) | None |
| O94876 | TMCC1 | S382 | ochoa | Transmembrane and coiled-coil domains protein 1 | Endoplasmic reticulum membrane protein that promotes endoplasmic reticulum-associated endosome fission (PubMed:30220460). Localizes to contact sites between the endoplasmic reticulum and endosomes and acts by promoting recruitment of the endoplasmic reticulum to endosome tubules for fission (PubMed:30220460). Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane (PubMed:30220460). {ECO:0000269|PubMed:30220460}. |
| O94880 | PHF14 | S244 | ochoa | PHD finger protein 14 | Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}. |
| O94929 | ABLIM3 | S286 | ochoa | Actin-binding LIM protein 3 (abLIM-3) (Actin-binding LIM protein family member 3) | May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity. {ECO:0000269|PubMed:17194709}. |
| O94964 | MTCL2 | S1320 | ochoa | Microtubule cross-linking factor 2 (SOGA family member 1) (Suppressor of glucose by autophagy) (Suppressor of glucose, autophagy-associated protein 1) [Cleaved into: N-terminal form; C-terminal 80 kDa form (80-kDa SOGA fragment)] | Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Preferentially acts on the perinuclear microtubules accumulated around the Golgi. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain (By similarity). Required for faithful chromosome segregation during mitosis (PubMed:33587225). Regulates autophagy by playing a role in the reduction of glucose production in an adiponectin- and insulin-dependent manner (By similarity). {ECO:0000250|UniProtKB:E1U8D0, ECO:0000269|PubMed:33587225}. |
| O94966 | USP19 | S897 | ochoa | Ubiquitin carboxyl-terminal hydrolase 19 (EC 3.4.19.12) (Deubiquitinating enzyme 19) (Ubiquitin thioesterase 19) (Ubiquitin-specific-processing protease 19) (Zinc finger MYND domain-containing protein 9) | Deubiquitinating enzyme that regulates the degradation of various proteins by removing ubiquitin moieties, thereby preventing their proteasomal degradation. Stabilizes RNF123, which promotes CDKN1B degradation and contributes to cell proliferation (By similarity). Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates (PubMed:19465887, PubMed:24356957). Mechanistically, deubiquitinates and thereby stabilizes several E3 ligases involved in the ERAD pathway including SYVN1 or MARCHF6 (PubMed:24356957). Regulates the stability of other E3 ligases including BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination (PubMed:21849505). Required for cells to mount an appropriate response to hypoxia by rescuing HIF1A from degradation in a non-catalytic manner and by mediating the deubiquitination of FUNDC1 (PubMed:22128162, PubMed:33978709). Attenuates mitochondrial damage and ferroptosis by targeting and stabilizing NADPH oxidase 4/NOX4 (PubMed:38943386). Negatively regulates TNF-alpha- and IL-1beta-triggered NF-kappa-B activation by hydrolyzing 'Lys-27'- and 'Lys-63'-linked polyubiquitin chains from MAP3K7 (PubMed:31127032). Modulates also the protein level and aggregation of polyQ-expanded huntingtin/HTT through HSP90AA1 (PubMed:33094816). {ECO:0000250|UniProtKB:Q3UJD6, ECO:0000250|UniProtKB:Q6J1Y9, ECO:0000269|PubMed:19465887, ECO:0000269|PubMed:21849505, ECO:0000269|PubMed:22128162, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:24356957, ECO:0000269|PubMed:31127032, ECO:0000269|PubMed:33094816, ECO:0000269|PubMed:33978709, ECO:0000269|PubMed:38943386}. |
| O94972 | TRIM37 | S817 | ochoa | E3 ubiquitin-protein ligase TRIM37 (EC 2.3.2.27) (Mulibrey nanism protein) (RING-type E3 ubiquitin transferase TRIM37) (Tripartite motif-containing protein 37) | E3 ubiquitin-protein ligase required to prevent centriole reduplication (PubMed:15885686, PubMed:23769972). Probably acts by ubiquitinating positive regulators of centriole reduplication (PubMed:23769972). Mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression: associates with some Polycomb group (PcG) multiprotein PRC2-like complex and mediates repression of target genes (PubMed:25470042). Also acts as a positive regulator of peroxisome import by mediating monoubiquitination of PEX5 at 'Lys-472': monoubiquitination promotes PEX5 stabilitation by preventing its polyubiquitination and degradation by the proteasome (PubMed:28724525). Has anti-HIV activity (PubMed:24317724). {ECO:0000269|PubMed:15885686, ECO:0000269|PubMed:23769972, ECO:0000269|PubMed:24317724, ECO:0000269|PubMed:25470042, ECO:0000269|PubMed:28724525}. |
| O94986 | CEP152 | S130 | ochoa | Centrosomal protein of 152 kDa (Cep152) | Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). Acts as a molecular scaffold facilitating the interaction of PLK4 and CPAP, 2 molecules involved in centriole formation (PubMed:20852615, PubMed:21059844). Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure (PubMed:24997597). Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (By similarity). Overexpression of CEP152 can drive amplification of centrioles (PubMed:20852615). {ECO:0000250|UniProtKB:A2AUM9, ECO:0000250|UniProtKB:Q498G2, ECO:0000269|PubMed:20852615, ECO:0000269|PubMed:21059844, ECO:0000269|PubMed:21131973}. |
| O94988 | FAM13A | S888 | ochoa | Protein FAM13A | None |
| O94992 | HEXIM1 | S252 | psp | Protein HEXIM1 (Cardiac lineage protein 1) (Estrogen down-regulated gene 1 protein) (Hexamethylene bis-acetamide-inducible protein 1) (Menage a quatre protein 1) | Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:14580347, PubMed:15201869, PubMed:15713661). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:12832472, PubMed:14580347, PubMed:15201869, PubMed:15713661). May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity (PubMed:15940264, PubMed:15941832, PubMed:17088550). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:12581153, ECO:0000269|PubMed:12832472, ECO:0000269|PubMed:14580347, ECO:0000269|PubMed:15201869, ECO:0000269|PubMed:15713661, ECO:0000269|PubMed:15940264, ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:17088550, ECO:0000269|PubMed:28712728}. |
| O95049 | TJP3 | S159 | ochoa | Tight junction protein ZO-3 (Tight junction protein 3) (Zona occludens protein 3) (Zonula occludens protein 3) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}. |
| O95071 | UBR5 | S143 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95071 | UBR5 | S169 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95163 | ELP1 | S173 | ochoa | Elongator complex protein 1 (ELP1) (IkappaB kinase complex-associated protein) (IKK complex-associated protein) (p150) | Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (By similarity). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (PubMed:9751059). {ECO:0000250|UniProtKB:Q06706, ECO:0000250|UniProtKB:Q7TT37, ECO:0000269|PubMed:9751059, ECO:0000303|PubMed:29332244}. |
| O95163 | ELP1 | S471 | ochoa | Elongator complex protein 1 (ELP1) (IkappaB kinase complex-associated protein) (IKK complex-associated protein) (p150) | Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (By similarity). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (PubMed:9751059). {ECO:0000250|UniProtKB:Q06706, ECO:0000250|UniProtKB:Q7TT37, ECO:0000269|PubMed:9751059, ECO:0000303|PubMed:29332244}. |
| O95197 | RTN3 | S395 | ochoa | Reticulon-3 (Homolog of ASY protein) (HAP) (Neuroendocrine-specific protein-like 2) (NSP-like protein 2) (Neuroendocrine-specific protein-like II) (NSP-like protein II) (NSPLII) | May be involved in membrane trafficking in the early secretory pathway. Inhibits BACE1 activity and amyloid precursor protein processing. May induce caspase-8 cascade and apoptosis. May favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress. Induces the formation of endoplasmic reticulum tubules (PubMed:25612671). Also acts as an inflammation-resolving regulator by interacting with both TRIM25 and RIGI, subsequently impairing RIGI 'Lys-63'-linked polyubiquitination leading to IRF3 and NF-kappa-B inhibition. {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16054885, ECO:0000269|PubMed:17031492, ECO:0000269|PubMed:17191123, ECO:0000269|PubMed:25612671}.; FUNCTION: (Microbial infection) Plays a positive role in viral replication and pathogenesis of enteroviruses. {ECO:0000269|PubMed:17182608}. |
| O95235 | KIF20A | S33 | ochoa | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95251 | KAT7 | S164 | ochoa | Histone acetyltransferase KAT7 (EC 2.3.1.48) (Histone acetyltransferase binding to ORC1) (Lysine acetyltransferase 7) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 2) (MYST-2) | Catalytic subunit of histone acetyltransferase HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby regulating various processes, such as gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance and embryonic development (PubMed:16387653, PubMed:21753189, PubMed:24065767, PubMed:26620551, PubMed:31767635, PubMed:31827282). Some complexes also catalyze acetylation of histone H4 at 'Lys-5', 'Lys-8' and 'Lys-12' (H4K5ac, H4K8ac and H4K12ac, respectively), regulating DNA replication initiation, regulating DNA replication initiation (PubMed:10438470, PubMed:19187766, PubMed:20129055, PubMed:24065767). Specificity of the HBO1 complexes is determined by the scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE (JADE1, JADE2 and JADE3) scaffold direct KAT7/HBO1 specificity towards histone H4 (PubMed:19187766, PubMed:20129055, PubMed:24065767, PubMed:26620551). H3K14ac promotes transcriptional elongation by facilitating the processivity of RNA polymerase II (PubMed:31827282). Acts as a key regulator of hematopoiesis by forming a complex with BRD1/BRPF2, directing KAT7/HBO1 specificity towards H3K14ac and promoting erythroid differentiation (PubMed:21753189). H3K14ac is also required for T-cell development (By similarity). KAT7/HBO1-mediated acetylation facilitates two consecutive steps, licensing and activation, in DNA replication initiation: H3K14ac facilitates the activation of replication origins, and histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac) facilitates chromatin loading of MCM complexes, promoting DNA replication licensing (PubMed:10438470, PubMed:11278932, PubMed:18832067, PubMed:19187766, PubMed:20129055, PubMed:21856198, PubMed:24065767, PubMed:26620551). Acts as a positive regulator of centromeric CENPA assembly: recruited to centromeres and mediates histone acetylation, thereby preventing centromere inactivation mediated by SUV39H1, possibly by increasing histone turnover/exchange (PubMed:27270040). Involved in nucleotide excision repair: phosphorylation by ATR in response to ultraviolet irradiation promotes its localization to DNA damage sites, where it mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites (PubMed:28719581). Acts as an inhibitor of NF-kappa-B independently of its histone acetyltransferase activity (PubMed:16997280). {ECO:0000250|UniProtKB:Q5SVQ0, ECO:0000269|PubMed:10438470, ECO:0000269|PubMed:11278932, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:16997280, ECO:0000269|PubMed:18832067, ECO:0000269|PubMed:19187766, ECO:0000269|PubMed:20129055, ECO:0000269|PubMed:21753189, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:26620551, ECO:0000269|PubMed:27270040, ECO:0000269|PubMed:28719581, ECO:0000269|PubMed:31767635, ECO:0000269|PubMed:31827282}.; FUNCTION: Plays a central role in the maintenance of leukemia stem cells in acute myeloid leukemia (AML) (PubMed:31827282). Acts by mediating acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby facilitating the processivity of RNA polymerase II to maintain the high expression of key genes, such as HOXA9 and HOXA10 that help to sustain the functional properties of leukemia stem cells (PubMed:31827282). {ECO:0000269|PubMed:31827282}. |
| O95260 | ATE1 | S179 | ochoa | Arginyl-tRNA--protein transferase 1 (Arginyltransferase 1) (R-transferase 1) (EC 2.3.2.8) (Arginine-tRNA--protein transferase 1) | Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein (PubMed:34893540). This arginylation is required for degradation of the protein via the ubiquitin pathway (PubMed:34893540). Does not arginylate cysteine residues (By similarity). {ECO:0000250|UniProtKB:Q9Z2A5, ECO:0000269|PubMed:34893540}. |
| O95359 | TACC2 | S749 | ochoa | Transforming acidic coiled-coil-containing protein 2 (Anti-Zuai-1) (AZU-1) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). May play a role in organizing centrosomal microtubules. May act as a tumor suppressor protein. May represent a tumor progression marker. {ECO:0000250, ECO:0000269|PubMed:10749935}. |
| O95400 | CD2BP2 | S34 | ochoa | CD2 antigen cytoplasmic tail-binding protein 2 (CD2 cytoplasmic domain-binding protein 2) (CD2 tail-binding protein 2) (U5 snRNP 52K protein) (U5-52K) | Involved in pre-mRNA splicing as component of the U5 snRNP complex that is involved in spliceosome assembly. {ECO:0000269|PubMed:15840814}. |
| O95425 | SVIL | S90 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95425 | SVIL | S193 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95571 | ETHE1 | S19 | ochoa | Persulfide dioxygenase ETHE1, mitochondrial (EC 1.13.11.18) (Ethylmalonic encephalopathy protein 1) (Hepatoma subtracted clone one protein) (Sulfur dioxygenase ETHE1) | Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase. First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (PubMed:12398897). {ECO:0000269|PubMed:12398897, ECO:0000269|PubMed:14732903, ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}. |
| O95613 | PCNT | S2345 | ochoa | Pericentrin (Kendrin) (Pericentrin-B) | Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:30420784}. |
| O95613 | PCNT | S2355 | ochoa | Pericentrin (Kendrin) (Pericentrin-B) | Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:30420784}. |
| O95747 | OXSR1 | S324 | ochoa | Serine/threonine-protein kinase OSR1 (EC 2.7.11.1) (Oxidative stress-responsive 1 protein) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:17721439, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:17721439). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (PubMed:23386621, PubMed:25362046). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (PubMed:29581290). Phosphorylates RELL1, RELL2 and RELT (PubMed:16389068, PubMed:28688764). Phosphorylates PAK1 (PubMed:14707132). Phosphorylates PLSCR1 in the presence of RELT (PubMed:22052202). {ECO:0000269|PubMed:14707132, ECO:0000269|PubMed:16389068, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:17721439, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:23386621, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:28688764, ECO:0000269|PubMed:29581290, ECO:0000269|PubMed:34289367}. |
| O95747 | OXSR1 | S425 | ochoa | Serine/threonine-protein kinase OSR1 (EC 2.7.11.1) (Oxidative stress-responsive 1 protein) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:17721439, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:17721439). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (PubMed:23386621, PubMed:25362046). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (PubMed:29581290). Phosphorylates RELL1, RELL2 and RELT (PubMed:16389068, PubMed:28688764). Phosphorylates PAK1 (PubMed:14707132). Phosphorylates PLSCR1 in the presence of RELT (PubMed:22052202). {ECO:0000269|PubMed:14707132, ECO:0000269|PubMed:16389068, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:17721439, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:23386621, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:28688764, ECO:0000269|PubMed:29581290, ECO:0000269|PubMed:34289367}. |
| O95793 | STAU1 | S390 | ochoa | Double-stranded RNA-binding protein Staufen homolog 1 | Binds double-stranded RNA (regardless of the sequence) and tubulin. May play a role in specific positioning of mRNAs at given sites in the cell by cross-linking cytoskeletal and RNA components, and in stimulating their translation at the site.; FUNCTION: (Microbial infection) Plays a role in virus particles production of many viruses including of HIV-1, HERV-K, ebola virus and influenza virus. Acts by interacting with various viral proteins involved in particle budding process. {ECO:0000269|PubMed:10325410, ECO:0000269|PubMed:18498651, ECO:0000269|PubMed:23926355, ECO:0000269|PubMed:30301857}. |
| O95810 | CAVIN2 | S364 | ochoa | Caveolae-associated protein 2 (Cavin-2) (PS-p68) (Phosphatidylserine-binding protein) (Serum deprivation-response protein) | Plays an important role in caveolar biogenesis and morphology. Regulates caveolae morphology by inducing membrane curvature within caveolae (PubMed:19525939). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in the lung and fat endothelia but not in the heart endothelia. Negatively regulates the size or stability of CAVIN complexes in the lung endothelial cells. May play a role in targeting PRKCA to caveolae (By similarity). {ECO:0000250|UniProtKB:Q66H98, ECO:0000269|PubMed:19525939}. |
| O95810 | CAVIN2 | S398 | ochoa | Caveolae-associated protein 2 (Cavin-2) (PS-p68) (Phosphatidylserine-binding protein) (Serum deprivation-response protein) | Plays an important role in caveolar biogenesis and morphology. Regulates caveolae morphology by inducing membrane curvature within caveolae (PubMed:19525939). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in the lung and fat endothelia but not in the heart endothelia. Negatively regulates the size or stability of CAVIN complexes in the lung endothelial cells. May play a role in targeting PRKCA to caveolae (By similarity). {ECO:0000250|UniProtKB:Q66H98, ECO:0000269|PubMed:19525939}. |
| O95997 | PTTG1 | S28 | ochoa | Securin (Esp1-associated protein) (Pituitary tumor-transforming gene 1 protein) (Tumor-transforming protein 1) (hPTTG) | Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11238996, ECO:0000269|PubMed:11371342, ECO:0000269|PubMed:12355087}. |
| O96011 | PEX11B | S160 | ochoa | Peroxisomal membrane protein 11B (Peroxin-11B) (Peroxisomal biogenesis factor 11B) (Protein PEX11 homolog beta) (PEX11-beta) | Involved in peroxisomal proliferation (PubMed:9792670). May regulate peroxisome division by recruiting the dynamin-related GTPase DNM1L to the peroxisomal membrane (PubMed:12618434). Promotes membrane protrusion and elongation on the peroxisomal surface (PubMed:20826455). {ECO:0000269|PubMed:12618434, ECO:0000269|PubMed:20826455, ECO:0000269|PubMed:9792670}. |
| O96013 | PAK4 | S167 | ochoa | Serine/threonine-protein kinase PAK 4 (EC 2.7.11.1) (p21-activated kinase 4) (PAK-4) | Serine/threonine-protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell adhesion turnover, cell migration, growth, proliferation or cell survival (PubMed:26598620). Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Promotes kinase-independent stabilization of RHOU, thereby contributing to focal adhesion disassembly during cell migration (PubMed:26598620). {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26598620, ECO:0000269|PubMed:26607847}. |
| P00367 | GLUD1 | S128 | ochoa | Glutamate dehydrogenase 1, mitochondrial (GDH 1) (EC 1.4.1.3) | Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:11254391, PubMed:16023112, PubMed:16959573). Plays a role in insulin homeostasis (PubMed:11297618, PubMed:9571255). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:9571255}. |
| P00533 | EGFR | S1162 | ochoa | Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}. |
| P00533 | EGFR | S1190 | ochoa|psp | Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}. |
| P01008 | SERPINC1 | S68 | ochoa | Antithrombin-III (ATIII) (Serpin C1) | Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade (PubMed:15140129, PubMed:15853774). AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa (PubMed:15140129). Its inhibitory activity is greatly enhanced in the presence of heparin. {ECO:0000269|PubMed:15140129, ECO:0000269|PubMed:15853774}. |
| P01275 | GCG | S150 | ochoa | Pro-glucagon [Cleaved into: Glicentin; Glicentin-related polypeptide (GRPP); Oxyntomodulin (OXM) (OXY); Glucagon; Glucagon-like peptide 1 (GLP-1) (Incretin hormone); Glucagon-like peptide 1(7-37) (GLP-1(7-37)); Glucagon-like peptide 1(7-36) (GLP-1(7-36)); Glucagon-like peptide 2 (GLP-2)] | [Glucagon]: Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. {ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12626323}.; FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6 (PubMed:22037645). Plays important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Has growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis (Probable). {ECO:0000269|PubMed:22037645, ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744, ECO:0000305|PubMed:14719035}.; FUNCTION: [Glucagon-like peptide 2]: Stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. {ECO:0000305|PubMed:10322410, ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744, ECO:0000305|PubMed:14719035}.; FUNCTION: [Oxyntomodulin]: Significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. {ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744}.; FUNCTION: [Glicentin]: May modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life. {ECO:0000305|PubMed:10605628, ECO:0000305|PubMed:12554744}. |
| P02545 | LMNA | S414 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02545 | LMNA | S632 | ochoa|psp | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02545 | LMNA | S636 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02671 | FGA | S274 | ochoa | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P02671 | FGA | S609 | ochoa|psp | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P02765 | AHSG | S328 | ochoa|psp | Alpha-2-HS-glycoprotein (Alpha-2-Z-globulin) (Ba-alpha-2-glycoprotein) (Fetuin-A) [Cleaved into: Alpha-2-HS-glycoprotein chain A; Alpha-2-HS-glycoprotein chain B] | Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions. |
| P04049 | RAF1 | S357 | ochoa|psp | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. |
| P04075 | ALDOA | S39 | ochoa | Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) | Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}. |
| P04439 | HLA-A | S343 | psp | HLA class I histocompatibility antigen, A alpha chain (Human leukocyte antigen A) (HLA-A) | Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:1402688, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:24395804, PubMed:2456340, PubMed:2784196, PubMed:28250417, PubMed:7504010, PubMed:7694806, PubMed:9862734). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728, PubMed:7679507). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17079320, PubMed:17189421, PubMed:20364150, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734). {ECO:0000269|PubMed:10449296, ECO:0000269|PubMed:12138174, ECO:0000269|PubMed:12393434, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:1402688, ECO:0000269|PubMed:15893615, ECO:0000269|PubMed:17079320, ECO:0000269|PubMed:17189421, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:19543285, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:21498667, ECO:0000269|PubMed:24192765, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:2456340, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:26929325, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7506728, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:9862734}.; FUNCTION: Allele A*01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus (PubMed:1402688, PubMed:17189421, PubMed:19177349, PubMed:20364150, PubMed:24395804, PubMed:25880248, PubMed:26758806, PubMed:30530481, PubMed:32887977, PubMed:7504010). A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413). {ECO:0000269|PubMed:1402688, ECO:0000269|PubMed:17189421, ECO:0000269|PubMed:18779413, ECO:0000269|PubMed:19177349, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:24395804, ECO:0000269|PubMed:25880248, ECO:0000269|PubMed:26758806, ECO:0000269|PubMed:30530481, ECO:0000269|PubMed:7504010}.; FUNCTION: Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors. {ECO:0000269|PubMed:11502003, ECO:0000269|PubMed:12138174, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:17079320, ECO:0000269|PubMed:18275829, ECO:0000269|PubMed:19542454, ECO:0000269|PubMed:20619457, ECO:0000269|PubMed:22245737, ECO:0000269|PubMed:26929325, ECO:0000269|PubMed:2784196, ECO:0000269|PubMed:28250417, ECO:0000269|PubMed:7694806, ECO:0000269|PubMed:7935798, ECO:0000269|PubMed:8630735, ECO:0000269|PubMed:8805302, ECO:0000269|PubMed:8906788, ECO:0000269|PubMed:9177355}.; FUNCTION: Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus (PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977, PubMed:7504010, PubMed:7679507, PubMed:9862734). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119). {ECO:0000269|PubMed:19543285, ECO:0000269|PubMed:21943705, ECO:0000269|PubMed:2456340, ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:7504010, ECO:0000269|PubMed:7679507, ECO:0000269|PubMed:9862734}.; FUNCTION: Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977). {ECO:0000269|PubMed:10449296, ECO:0000269|PubMed:32887977}.; FUNCTION: Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. {ECO:0000269|PubMed:17182537}.; FUNCTION: Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:12393434, PubMed:20844028, PubMed:24192765, PubMed:9047241). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829). {ECO:0000269|PubMed:12393434, ECO:0000269|PubMed:17182537, ECO:0000269|PubMed:18502829, ECO:0000269|PubMed:20844028, ECO:0000269|PubMed:24192765, ECO:0000269|PubMed:9047241}.; FUNCTION: Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus. {ECO:0000269|PubMed:15893615}.; FUNCTION: Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus. {ECO:0000269|PubMed:8622959}.; FUNCTION: Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response. {ECO:0000269|PubMed:17182537}.; FUNCTION: Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor. {ECO:0000269|PubMed:1448153, ECO:0000269|PubMed:1448154, ECO:0000269|PubMed:2784196}.; FUNCTION: Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection. {ECO:0000269|PubMed:21498667}. |
| P04626 | ERBB2 | S728 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P04626 | ERBB2 | S1083 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P04843 | RPN1 | S62 | ochoa | Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1 (Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 67 kDa subunit) (Ribophorin I) (RPN-I) (Ribophorin-1) | Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (PubMed:31831667). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (By similarity). {ECO:0000250|UniProtKB:E2RQ08, ECO:0000269|PubMed:31831667, ECO:0000269|PubMed:39567208}. |
| P04920 | SLC4A2 | S446 | ochoa | Anion exchange protein 2 (AE 2) (Anion exchanger 2) (Non-erythroid band 3-like protein) (BND3L) (Solute carrier family 4 member 2) | Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15184086, PubMed:34668226). Plays an important role in osteoclast differentiation and function (PubMed:34668226). Regulates bone resorption and calpain-dependent actin cytoskeleton organization in osteoclasts via anion exchange-dependent control of pH (By similarity). Essential for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation, modulating CD8(+) T-cell responses (By similarity). {ECO:0000250|UniProtKB:P13808, ECO:0000269|PubMed:15184086, ECO:0000269|PubMed:34668226}. |
| P05023 | ATP1A1 | S668 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P05060 | CHGB | S367 | ochoa | Secretogranin-1 (Chromogranin-B) (CgB) (Secretogranin I) (SgI) [Cleaved into: PE-11; GAWK peptide; CCB peptide] | Secretogranin-1 is a neuroendocrine secretory granule protein, which may be the precursor for other biologically active peptides. |
| P05455 | SSB | S350 | ochoa | Lupus La protein (La autoantigen) (La ribonucleoprotein) (Sjoegren syndrome type B antigen) (SS-B) | Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation (PubMed:2470590, PubMed:3192525). In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12384597). {ECO:0000269|PubMed:12384597, ECO:0000269|PubMed:2470590, ECO:0000269|PubMed:3192525}. |
| P06213 | INSR | S1033 | psp | Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta] | Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity). {ECO:0000250|UniProtKB:P15208, ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}. |
| P06239 | LCK | S54 | ochoa | Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) | Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}. |
| P06576 | ATP5F1B | S415 | ochoa | ATP synthase F(1) complex subunit beta, mitochondrial (EC 7.1.2.2) (ATP synthase F1 subunit beta) | Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable) (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain (PubMed:37244256). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:25168243, ECO:0000305|PubMed:36239646, ECO:0000305|PubMed:37244256}. |
| P06734 | FCER2 | S265 | psp | Low affinity immunoglobulin epsilon Fc receptor (BLAST-2) (C-type lectin domain family 4 member J) (Fc-epsilon-RII) (Immunoglobulin E-binding factor) (Lymphocyte IgE receptor) (CD antigen CD23) [Cleaved into: Low affinity immunoglobulin epsilon Fc receptor membrane-bound form; Low affinity immunoglobulin epsilon Fc receptor soluble form] | Low-affinity receptor for immunoglobulin E (IgE) and CR2/CD21. Has essential roles in the regulation of IgE production and in the differentiation of B cells. On B cells, initiates IgE-dependent antigen uptake and presentation to T cells (PubMed:2167225). On macrophages, upon IgE binding and antigen cross-linking induces intracellular killing of parasites through activation of L-Arginine-nitric oxide pathway (PubMed:7544003). {ECO:0000269|PubMed:2167225, ECO:0000269|PubMed:7544003}. |
| P06748 | NPM1 | S106 | ochoa|psp | Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) | Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}. |
| P07384 | CAPN1 | S379 | psp | Calpain-1 catalytic subunit (EC 3.4.22.52) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (Calpain-1 large subunit) (Cell proliferation-inducing gene 30 protein) (Micromolar-calpain) (muCANP) | Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:19617626, PubMed:21531719, PubMed:2400579). Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409' (PubMed:23707407). Cleaves and activates caspase-7 (CASP7) (PubMed:19617626). {ECO:0000269|PubMed:19617626, ECO:0000269|PubMed:21531719, ECO:0000269|PubMed:23707407, ECO:0000269|PubMed:2400579}. |
| P07910 | HNRNPC | S107 | ochoa | Heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C1/C2) | Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). {ECO:0000269|PubMed:12509468, ECO:0000269|PubMed:16010978, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:7567451, ECO:0000269|PubMed:8264621}. |
| P08047 | SP1 | S732 | psp | Transcription factor Sp1 | Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}. |
| P08069 | IGF1R | S1009 | ochoa | Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain] | Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. |
| P09651 | HNRNPA1 | S142 | ochoa | Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) (Helix-destabilizing protein) (Single-strand RNA-binding protein) (hnRNP core protein A1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed] | Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection (PubMed:17371836). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1 (PubMed:31498791). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:20010808, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:31498791}.; FUNCTION: (Microbial infection) May play a role in HCV RNA replication. {ECO:0000269|PubMed:17229681}.; FUNCTION: (Microbial infection) Cleavage by Enterovirus 71 protease 3C results in increased translation of apoptosis protease activating factor APAF1, leading to apoptosis. {ECO:0000269|PubMed:17229681}. |
| P09972 | ALDOC | S39 | ochoa | Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) | None |
| P0C7P1 | RBMY1D | S473 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member D | RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis. |
| P0C7T5 | ATXN1L | S615 | ochoa | Ataxin-1-like (Brother of ataxin-1) (Brother of ATXN1) | Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression (PubMed:21475249). Can suppress ATXN1 cytotoxicity in spinocerebellar ataxia type 1 (SCA1). In concert with CIC and ATXN1, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P0C7T6, ECO:0000269|PubMed:21475249}. |
| P0DJ93 | SMIM13 | S50 | ochoa | Small integral membrane protein 13 | None |
| P0DJD0 | RGPD1 | S1208 | ochoa | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P0DJD1 | RGPD2 | S1216 | ochoa | RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) | None |
| P0DJD3 | RBMY1A1 | S473 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member A1 (RNA-binding motif protein 1) (RNA-binding motif protein 2) (Y chromosome RNA recognition motif 1) (hRBMY) | RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:8269511}. |
| P0DJD4 | RBMY1C | S473 | ochoa | RNA-binding motif protein, Y chromosome, family 1 member C | RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs. |
| P10244 | MYBL2 | S401 | ochoa | Myb-related protein B (B-Myb) (Myb-like protein 2) | Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene. {ECO:0000269|PubMed:10770937}. |
| P10398 | ARAF | S165 | ochoa | Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks) | Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789). {ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:36402789}.; FUNCTION: [Isoform 2]: Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. {ECO:0000269|PubMed:22609986}. |
| P10398 | ARAF | S250 | ochoa | Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks) | Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789). {ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:36402789}.; FUNCTION: [Isoform 2]: Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. {ECO:0000269|PubMed:22609986}. |
| P10588 | NR2F6 | S149 | ochoa | Nuclear receptor subfamily 2 group F member 6 (V-erbA-related protein 2) (EAR-2) | Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). {ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:10713182, ECO:0000269|PubMed:11682620, ECO:0000269|PubMed:18701084}. |
| P10589 | NR2F1 | S77 | ochoa | COUP transcription factor 1 (COUP-TF1) (COUP transcription factor I) (COUP-TF I) (Nuclear receptor subfamily 2 group F member 1) (V-erbA-related protein 3) (EAR-3) | Coup (chicken ovalbumin upstream promoter) transcription factor binds to the ovalbumin promoter and, in conjunction with another protein (S300-II) stimulates initiation of transcription. Binds to both direct repeats and palindromes of the 5'-AGGTCA-3' motif. Represses transcriptional activity of LHCG. {ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:11682620}. |
| P10636 | MAPT | S56 | ochoa | Microtubule-associated protein tau (Neurofibrillary tangle protein) (Paired helical filament-tau) (PHF-tau) | Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both (PubMed:21985311, PubMed:32961270). Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization. {ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:32961270}. |
| P10721 | KIT | S746 | psp | Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117) | Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12511554, ECO:0000269|PubMed:12878163, ECO:0000269|PubMed:17904548, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:9528781}. |
| P11274 | BCR | S221 | ochoa | Breakpoint cluster region protein (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-26) | Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. |
| P11274 | BCR | S429 | ochoa | Breakpoint cluster region protein (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-26) | Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. |
| P11413 | G6PD | S486 | psp | Glucose-6-phosphate 1-dehydrogenase (G6PD) (EC 1.1.1.49) | Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:35122041, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:743300}. |
| P12830 | CDH1 | S838 | psp | Cadherin-1 (CAM 120/80) (Epithelial cadherin) (E-cadherin) (Uvomorulin) (CD antigen CD324) [Cleaved into: E-Cad/CTF1; E-Cad/CTF2; E-Cad/CTF3] | Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells (PubMed:11976333). Promotes organization of radial actin fiber structure and cellular response to contractile forces, via its interaction with AMOTL2 which facilitates anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane (By similarity). Plays a role in the early stages of desmosome cell-cell junction formation via facilitating the recruitment of DSG2 and DSP to desmosome plaques (PubMed:29999492). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7. {ECO:0000250|UniProtKB:F1PAA9, ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:16417575, ECO:0000269|PubMed:29999492}.; FUNCTION: E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production. {ECO:0000269|PubMed:16417575}.; FUNCTION: (Microbial infection) Serves as a receptor for Listeria monocytogenes; internalin A (InlA) binds to this protein and promotes uptake of the bacteria. {ECO:0000269|PubMed:10406800, ECO:0000269|PubMed:17540170, ECO:0000269|PubMed:8601315}. |
| P12883 | MYH7 | S1102 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P12883 | MYH7 | S1518 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P13349 | MYF5 | S49 | psp | Myogenic factor 5 (Myf-5) (Class C basic helix-loop-helix protein 2) (bHLHc2) | Transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation (PubMed:29887215). Together with MYOG and MYOD1, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein. {ECO:0000269|PubMed:2721498, ECO:0000269|PubMed:29887215}. |
| P13804 | ETFA | S182 | ochoa | Electron transfer flavoprotein subunit alpha, mitochondrial (Alpha-ETF) | Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:10356313, PubMed:15159392, PubMed:15975918, PubMed:27499296, PubMed:9334218). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:9334218). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:1430199, PubMed:1882842). {ECO:0000269|PubMed:10356313, ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:1430199, ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:27499296, ECO:0000269|PubMed:9334218, ECO:0000303|PubMed:17941859, ECO:0000305|PubMed:1882842}. |
| P13994 | YJU2B | S366 | ochoa | Probable splicing factor YJU2B (Coiled-coil domain-containing protein 130) | May be involved in mRNA splicing. {ECO:0000250|UniProtKB:Q9BW85}. |
| P14618 | PKM | S205 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P15056 | BRAF | S465 | ochoa|psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P15170 | GSPT1 | S36 | ochoa | Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (Eukaryotic peptide chain release factor subunit 3a) (eRF3a) (EC 3.6.5.-) (G1 to S phase transition protein 1 homolog) | GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA (PubMed:15987998, PubMed:19417105, PubMed:2511002, PubMed:27863242). GSPT1/ERF3A mediates ETF1/ERF1 delivery to stop codons: The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site (PubMed:27863242). GTP hydrolysis by GSPT1/ERF3A induces a conformational change that leads to its dissociation, permitting ETF1/ERF1 to accommodate fully in the A-site (PubMed:16777602, PubMed:27863242). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:24486019). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371). {ECO:0000269|PubMed:15987998, ECO:0000269|PubMed:16777602, ECO:0000269|PubMed:19417105, ECO:0000269|PubMed:24486019, ECO:0000269|PubMed:2511002, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:30682371}. |
| P15260 | IFNGR1 | S391 | ochoa | Interferon gamma receptor 1 (IFN-gamma receptor 1) (IFN-gamma-R1) (CDw119) (Interferon gamma receptor alpha-chain) (IFN-gamma-R-alpha) (CD antigen CD119) | Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:20015550). Associates with transmembrane accessory factor IFNGR2 to form a functional receptor (PubMed:10986460, PubMed:2971451, PubMed:7615558, PubMed:7617032, PubMed:7673114). Upon ligand binding, the intracellular domain of IFNGR1 opens out to allow association of downstream signaling components JAK1 and JAK2. In turn, activated JAK1 phosphorylates IFNGR1 to form a docking site for STAT1. Subsequent phosphorylation of STAT1 leads to dimerization, translocation to the nucleus, and stimulation of target gene transcription (PubMed:28883123). STAT3 can also be activated in a similar manner although activation seems weaker. IFNGR1 intracellular domain phosphorylation also provides a docking site for SOCS1 that regulates the JAK-STAT pathway by competing with STAT1 binding to IFNGR1 (By similarity). {ECO:0000250|UniProtKB:P15261, ECO:0000269|PubMed:10986460, ECO:0000269|PubMed:20015550, ECO:0000269|PubMed:28883123, ECO:0000269|PubMed:2971451, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7617032, ECO:0000269|PubMed:7673114}. |
| P15391 | CD19 | S342 | ochoa | B-lymphocyte antigen CD19 (B-lymphocyte surface antigen B4) (Differentiation antigen CD19) (T-cell surface antigen Leu-12) (CD antigen CD19) | Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:1373518, PubMed:16672701, PubMed:2463100). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:12387743, PubMed:16672701, PubMed:9317126, PubMed:9382888). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:1373518, PubMed:2463100). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:12387743, PubMed:16672701, PubMed:9317126). {ECO:0000250|UniProtKB:P25918, ECO:0000269|PubMed:12387743, ECO:0000269|PubMed:1373518, ECO:0000269|PubMed:16672701, ECO:0000269|PubMed:2463100, ECO:0000269|PubMed:29523808, ECO:0000269|PubMed:9317126, ECO:0000269|PubMed:9382888}. |
| P15884 | TCF4 | S312 | ochoa | Transcription factor 4 (TCF-4) (Class B basic helix-loop-helix protein 19) (bHLHb19) (Immunoglobulin transcription factor 2) (ITF-2) (SL3-3 enhancer factor 2) (SEF-2) | Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'. {ECO:0000250}. |
| P15884 | TCF4 | S317 | ochoa | Transcription factor 4 (TCF-4) (Class B basic helix-loop-helix protein 19) (bHLHb19) (Immunoglobulin transcription factor 2) (ITF-2) (SL3-3 enhancer factor 2) (SEF-2) | Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'. {ECO:0000250}. |
| P15924 | DSP | S178 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P16144 | ITGB4 | S1360 | psp | Integrin beta-4 (GP150) (CD antigen CD104) | Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}. |
| P16150 | SPN | S322 | ochoa | Leukosialin (GPL115) (Galactoglycoprotein) (GALGP) (Leukocyte sialoglycoprotein) (Sialophorin) (CD antigen CD43) [Cleaved into: CD43 cytoplasmic tail (CD43-ct) (CD43ct)] | Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells (PubMed:18036228). Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (PubMed:24328034). Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1 (By similarity). {ECO:0000250|UniProtKB:P15702, ECO:0000269|PubMed:18036228, ECO:0000269|PubMed:24328034}.; FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic signals, promoting cell survival. {ECO:0000250|UniProtKB:P15702}. |
| P16150 | SPN | S328 | ochoa | Leukosialin (GPL115) (Galactoglycoprotein) (GALGP) (Leukocyte sialoglycoprotein) (Sialophorin) (CD antigen CD43) [Cleaved into: CD43 cytoplasmic tail (CD43-ct) (CD43ct)] | Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells (PubMed:18036228). Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (PubMed:24328034). Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1 (By similarity). {ECO:0000250|UniProtKB:P15702, ECO:0000269|PubMed:18036228, ECO:0000269|PubMed:24328034}.; FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic signals, promoting cell survival. {ECO:0000250|UniProtKB:P15702}. |
| P16150 | SPN | S355 | ochoa | Leukosialin (GPL115) (Galactoglycoprotein) (GALGP) (Leukocyte sialoglycoprotein) (Sialophorin) (CD antigen CD43) [Cleaved into: CD43 cytoplasmic tail (CD43-ct) (CD43ct)] | Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells (PubMed:18036228). Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (PubMed:24328034). Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1 (By similarity). {ECO:0000250|UniProtKB:P15702, ECO:0000269|PubMed:18036228, ECO:0000269|PubMed:24328034}.; FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic signals, promoting cell survival. {ECO:0000250|UniProtKB:P15702}. |
| P16885 | PLCG2 | S677 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-gamma-2) (Phospholipase C-IV) (PLC-IV) (Phospholipase C-gamma-2) (PLC-gamma-2) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. {ECO:0000269|PubMed:23000145}. |
| P16989 | YBX3 | S201 | ochoa | Y-box-binding protein 3 (Cold shock domain-containing protein A) (DNA-binding protein A) (Single-strand DNA-binding protein NF-GMB) | Binds to the GM-CSF promoter. Seems to act as a repressor. Also binds to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression (By similarity). {ECO:0000250}. |
| P16989 | YBX3 | S203 | ochoa | Y-box-binding protein 3 (Cold shock domain-containing protein A) (DNA-binding protein A) (Single-strand DNA-binding protein NF-GMB) | Binds to the GM-CSF promoter. Seems to act as a repressor. Also binds to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression (By similarity). {ECO:0000250}. |
| P17096 | HMGA1 | S44 | ochoa|psp | High mobility group protein HMG-I/HMG-Y (HMG-I(Y)) (High mobility group AT-hook protein 1) (High mobility group protein A1) (High mobility group protein R) | HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions. |
| P17600 | SYN1 | S390 | ochoa | Synapsin-1 (Brain protein 4.1) (Synapsin I) | Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (PubMed:21441247, PubMed:23406870). Also involved in the regulation of axon outgrowth and synaptogenesis (By similarity). The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level (By similarity). {ECO:0000250|UniProtKB:O88935, ECO:0000250|UniProtKB:P09951, ECO:0000269|PubMed:21441247, ECO:0000269|PubMed:23406870}. |
| P17600 | SYN1 | S432 | ochoa | Synapsin-1 (Brain protein 4.1) (Synapsin I) | Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (PubMed:21441247, PubMed:23406870). Also involved in the regulation of axon outgrowth and synaptogenesis (By similarity). The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level (By similarity). {ECO:0000250|UniProtKB:O88935, ECO:0000250|UniProtKB:P09951, ECO:0000269|PubMed:21441247, ECO:0000269|PubMed:23406870}. |
| P17661 | DES | S438 | ochoa | Desmin | Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Required for nuclear membrane integrity, via anchoring at the cell tip and nuclear envelope, resulting in maintenance of microtubule-derived intracellular mechanical forces (By similarity). Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity). {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190, ECO:0000303|PubMed:25358400}. |
| P17844 | DDX5 | S24 | ochoa | Probable ATP-dependent RNA helicase DDX5 (EC 3.6.4.13) (DEAD box protein 5) (RNA helicase p68) | Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as a transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. {ECO:0000269|PubMed:12527917, ECO:0000269|PubMed:15298701, ECO:0000269|PubMed:15660129, ECO:0000269|PubMed:17011493, ECO:0000269|PubMed:17960593, ECO:0000269|PubMed:18829551, ECO:0000269|PubMed:19718048, ECO:0000269|PubMed:21343338}. |
| P17844 | DDX5 | S480 | ochoa | Probable ATP-dependent RNA helicase DDX5 (EC 3.6.4.13) (DEAD box protein 5) (RNA helicase p68) | Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as a transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. {ECO:0000269|PubMed:12527917, ECO:0000269|PubMed:15298701, ECO:0000269|PubMed:15660129, ECO:0000269|PubMed:17011493, ECO:0000269|PubMed:17960593, ECO:0000269|PubMed:18829551, ECO:0000269|PubMed:19718048, ECO:0000269|PubMed:21343338}. |
| P18583 | SON | S2181 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P18887 | XRCC1 | S234 | ochoa | DNA repair protein XRCC1 (X-ray repair cross-complementing protein 1) | Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes (PubMed:11163244, PubMed:28002403). Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity (PubMed:28002403, PubMed:34102106, PubMed:34811483). Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity (PubMed:14500814, PubMed:34102106, PubMed:34811483). {ECO:0000269|PubMed:11163244, ECO:0000269|PubMed:14500814, ECO:0000269|PubMed:28002403, ECO:0000269|PubMed:34102106, ECO:0000269|PubMed:34811483}. |
| P19174 | PLCG1 | S1233 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (EC 3.1.4.11) (PLC-148) (Phosphoinositide phospholipase C-gamma-1) (Phospholipase C-II) (PLC-II) (Phospholipase C-gamma-1) (PLC-gamma-1) | Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin reorganization and cell migration (PubMed:17229814). Guanine nucleotide exchange factor that binds the GTPase DNM1 and catalyzes the dissociation of GDP, allowing a GTP molecule to bind in its place, therefore enhancing DNM1-dependent endocytosis (By similarity). {ECO:0000250|UniProtKB:P10686, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:37422272}. |
| P19174 | PLCG1 | S1248 | ochoa|psp | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (EC 3.1.4.11) (PLC-148) (Phosphoinositide phospholipase C-gamma-1) (Phospholipase C-II) (PLC-II) (Phospholipase C-gamma-1) (PLC-gamma-1) | Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin reorganization and cell migration (PubMed:17229814). Guanine nucleotide exchange factor that binds the GTPase DNM1 and catalyzes the dissociation of GDP, allowing a GTP molecule to bind in its place, therefore enhancing DNM1-dependent endocytosis (By similarity). {ECO:0000250|UniProtKB:P10686, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:37422272}. |
| P19971 | TYMP | S23 | ochoa | Thymidine phosphorylase (TP) (EC 2.4.2.4) (Gliostatin) (Platelet-derived endothelial cell growth factor) (PD-ECGF) (TdRPase) | May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro. {ECO:0000269|PubMed:1590793}.; FUNCTION: Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. {ECO:0000269|PubMed:1590793}. |
| P20338 | RAB4A | S190 | ochoa | Ras-related protein Rab-4A (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:15907487, PubMed:16034420). RAB4A is involved in protein transport (PubMed:29425100). Also plays a role in vesicular traffic. Mediates VEGFR2 endosomal trafficking to enhance VEGFR2 signaling (PubMed:29425100). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (By similarity). {ECO:0000250|UniProtKB:P56371, ECO:0000269|PubMed:15907487, ECO:0000269|PubMed:16034420, ECO:0000269|PubMed:29425100}. |
| P20393 | NR1D1 | S59 | psp | Nuclear receptor subfamily 1 group D member 1 (Rev-erbA-alpha) (V-erbA-related protein 1) (EAR-1) | Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity). {ECO:0000250|UniProtKB:Q3UV55, ECO:0000269|PubMed:12021280, ECO:0000269|PubMed:15761026, ECO:0000269|PubMed:16968709, ECO:0000269|PubMed:18006707, ECO:0000269|PubMed:19710360, ECO:0000269|PubMed:1971514, ECO:0000269|PubMed:21479263, ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:2539258}. |
| P20839 | IMPDH1 | S416 | ochoa | Inosine-5'-monophosphate dehydrogenase 1 (IMP dehydrogenase 1) (IMPD 1) (IMPDH 1) (EC 1.1.1.205) (IMPDH-I) | Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors. |
| P21333 | FLNA | S1081 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | S1084 | ochoa|psp | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21399 | ACO1 | S778 | ochoa | Cytoplasmic aconitate hydratase (Aconitase) (EC 4.2.1.3) (Citrate hydro-lyase) (Ferritin repressor protein) (Iron regulatory protein 1) (IRP1) (Iron-responsive element-binding protein 1) (IRE-BP 1) | Bifunctional iron sensor that switches between 2 activities depending on iron availability (PubMed:1281544, PubMed:1946430, PubMed:8041788). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization (PubMed:1281544, PubMed:1946430, PubMed:23891004, PubMed:8041788). Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA (PubMed:1281544, PubMed:1946430, PubMed:23891004, PubMed:8041788). {ECO:0000269|PubMed:1281544, ECO:0000269|PubMed:1946430, ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:8041788}.; FUNCTION: Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate. {ECO:0000269|PubMed:1281544, ECO:0000269|PubMed:1946430, ECO:0000269|PubMed:8041788}. |
| P21709 | EPHA1 | S910 | ochoa | Ephrin type-A receptor 1 (hEpha1) (EC 2.7.10.1) (EPH tyrosine kinase) (EPH tyrosine kinase 1) (Erythropoietin-producing hepatoma receptor) (Tyrosine-protein kinase receptor EPH) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217, ECO:0000269|PubMed:20043122}. |
| P21860 | ERBB3 | S1104 | ochoa | Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-3) (Tyrosine kinase-type cell surface receptor HER3) | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908). {ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:27416908}. |
| P22059 | OSBP | S338 | ochoa | Oxysterol-binding protein 1 | Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum (PubMed:24209621). Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol (PubMed:15746430, PubMed:17428193). Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly (PubMed:15746430). Regulates cholesterol efflux by decreasing ABCA1 stability (PubMed:18450749). {ECO:0000269|PubMed:15746430, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18450749, ECO:0000269|PubMed:24209621}. |
| P22681 | CBL | S439 | ochoa | E3 ubiquitin-protein ligase CBL (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene) (Proto-oncogene c-Cbl) (RING finger protein 55) (RING-type E3 ubiquitin transferase CBL) (Signal transduction protein CBL) | E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, PubMed:19689429, PubMed:21596750, PubMed:28381567). Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signaling (PubMed:15190072, PubMed:18374639, PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates NECTIN1 following association between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, leading to NECTIN1 removal from cell surface (PubMed:28381567). Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis (PubMed:15190072, PubMed:18374639). Essential for osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:P22682, ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17094949, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:28381567}. |
| P22681 | CBL | S441 | ochoa | E3 ubiquitin-protein ligase CBL (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene) (Proto-oncogene c-Cbl) (RING finger protein 55) (RING-type E3 ubiquitin transferase CBL) (Signal transduction protein CBL) | E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, PubMed:19689429, PubMed:21596750, PubMed:28381567). Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signaling (PubMed:15190072, PubMed:18374639, PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates NECTIN1 following association between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, leading to NECTIN1 removal from cell surface (PubMed:28381567). Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis (PubMed:15190072, PubMed:18374639). Essential for osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:P22682, ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17094949, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:28381567}. |
| P22735 | TGM1 | S95 | ochoa | Protein-glutamine gamma-glutamyltransferase K (EC 2.3.2.13) (Epidermal TGase) (Transglutaminase K) (TG(K)) (TGK) (TGase K) (Transglutaminase-1) (TGase-1) | Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Responsible for cross-linking epidermal proteins during formation of the stratum corneum. Involved in cell proliferation (PubMed:26220141). {ECO:0000269|PubMed:26220141}. |
| P23588 | EIF4B | S283 | ochoa | Eukaryotic translation initiation factor 4B (eIF-4B) | Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F. |
| P25054 | APC | S127 | ochoa | Adenomatous polyposis coli protein (Protein APC) (Deleted in polyposis 2.5) | Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization. {ECO:0000250|UniProtKB:Q61315, ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:17293347, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19151759, ECO:0000269|PubMed:19893577, ECO:0000269|PubMed:20937854}. |
| P25440 | BRD2 | S597 | ochoa | Bromodomain-containing protein 2 (O27.1.1) | Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures (PubMed:17148447, PubMed:17848202, PubMed:18406326, PubMed:20048151, PubMed:20709061, PubMed:20871596). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:28262505). Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation (PubMed:35410381). Also recognizes and binds acetylated non-histone proteins, such as STAT3 (PubMed:28262505). Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin (PubMed:28262505). In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). {ECO:0000269|PubMed:17148447, ECO:0000269|PubMed:17848202, ECO:0000269|PubMed:18406326, ECO:0000269|PubMed:20048151, ECO:0000269|PubMed:20709061, ECO:0000269|PubMed:20871596, ECO:0000269|PubMed:28262505, ECO:0000269|PubMed:35410381, ECO:0000269|PubMed:37731000}. |
| P26639 | TARS1 | S39 | ochoa | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P27816 | MAP4 | S94 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P27987 | ITPKB | S31 | ochoa | Inositol-trisphosphate 3-kinase B (EC 2.7.1.127) (Inositol 1,4,5-trisphosphate 3-kinase B) (IP3 3-kinase B) (IP3K B) (InsP 3-kinase B) | Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis. {ECO:0000269|PubMed:11846419, ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:1654894}. |
| P27987 | ITPKB | S456 | ochoa | Inositol-trisphosphate 3-kinase B (EC 2.7.1.127) (Inositol 1,4,5-trisphosphate 3-kinase B) (IP3 3-kinase B) (IP3K B) (InsP 3-kinase B) | Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis. {ECO:0000269|PubMed:11846419, ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:1654894}. |
| P28290 | ITPRID2 | S111 | ochoa | Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) | None |
| P28290 | ITPRID2 | S366 | ochoa | Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) | None |
| P28290 | ITPRID2 | S1165 | ochoa | Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) | None |
| P29274 | ADORA2A | S329 | ochoa | Adenosine receptor A2a | Receptor for adenosine (By similarity). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity). {ECO:0000250|UniProtKB:P11617}. |
| P29353 | SHC1 | S80 | ochoa | SHC-transforming protein 1 (SHC-transforming protein 3) (SHC-transforming protein A) (Src homology 2 domain-containing-transforming protein C1) (SH2 domain protein C1) | Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. {ECO:0000250, ECO:0000269|PubMed:14665640}. |
| P29353 | SHC1 | S453 | ochoa | SHC-transforming protein 1 (SHC-transforming protein 3) (SHC-transforming protein A) (Src homology 2 domain-containing-transforming protein C1) (SH2 domain protein C1) | Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. {ECO:0000250, ECO:0000269|PubMed:14665640}. |
| P29536 | LMOD1 | S44 | ochoa | Leiomodin-1 (64 kDa autoantigen 1D) (64 kDa autoantigen 1D3) (64 kDa autoantigen D1) (Leiomodin, muscle form) (Smooth muscle leiomodin) (SM-Lmod) (Thyroid-associated ophthalmopathy autoantigen) | Required for proper contractility of visceral smooth muscle cells (PubMed:28292896). Mediates nucleation of actin filaments. {ECO:0000269|PubMed:26370058, ECO:0000269|PubMed:28292896}. |
| P29590 | PML | S535 | ochoa | Protein PML (E3 SUMO-protein ligase PML) (EC 2.3.2.-) (Promyelocytic leukemia protein) (RING finger protein 71) (RING-type E3 SUMO transferase PML) (Tripartite motif-containing protein 19) (TRIM19) | Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration. {ECO:0000269|PubMed:11500381, ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:18391071}.; FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HHV-5) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. Functions as an E3 SUMO-protein ligase that sumoylates (HHV-5) immediate early protein IE1, thereby participating in the antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 and PML-6 display the highest levels of sumoylation activity (PubMed:20972456, PubMed:28250117). {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}. |
| P29692 | EEF1D | S64 | ochoa | Elongation factor 1-delta (EF-1-delta) (Antigen NY-CO-4) | [Isoform 1]: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.; FUNCTION: [Isoform 2]: Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE). |
| P29728 | OAS2 | S396 | ochoa | 2'-5'-oligoadenylate synthase 2 ((2-5')oligo(A) synthase 2) (2-5A synthase 2) (EC 2.7.7.84) (p69 OAS / p71 OAS) (p69OAS / p71OAS) | Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:10464285, PubMed:9880569). Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation (PubMed:10464285, PubMed:11682059, PubMed:9880569). Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:10464285, PubMed:9880569). Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL (PubMed:21142819). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation (PubMed:21142819). May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates (By similarity). Non-infected lobules would not be affected, allowing efficient pup feeding during infection (By similarity). {ECO:0000250|UniProtKB:E9Q9A9, ECO:0000269|PubMed:10464285, ECO:0000269|PubMed:11682059, ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:9880569, ECO:0000303|PubMed:21142819}. |
| P30305 | CDC25B | S42 | ochoa|psp | M-phase inducer phosphatase 2 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25B) | Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression (PubMed:1836978, PubMed:20360007). Directly dephosphorylates CDK1 and stimulates its kinase activity (PubMed:20360007). Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner (PubMed:17332740). The three isoforms seem to have a different level of activity (PubMed:1836978). {ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:1836978, ECO:0000269|PubMed:20360007}. |
| P30518 | AVPR2 | S255 | psp | Vasopressin V2 receptor (V2R) (AVPR V2) (Antidiuretic hormone receptor) (Renal-type arginine vasopressin receptor) | Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption. {ECO:0000269|PubMed:19440390}. |
| P31040 | SDHA | S530 | ochoa | Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (EC 1.3.5.1) (Flavoprotein subunit of complex II) (Fp) (Malate dehydrogenase [quinone] flavoprotein subunit) (EC 1.1.5.-) | Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:10746566, PubMed:24781757). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate (By similarity). Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate (By similarity). Can act as a tumor suppressor (PubMed:20484225). {ECO:0000250|UniProtKB:P31039, ECO:0000269|PubMed:10746566, ECO:0000269|PubMed:20484225, ECO:0000269|PubMed:24781757}. |
| P31277 | HOXD11 | S241 | ochoa | Homeobox protein Hox-D11 (Homeobox protein Hox-4F) | Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. |
| P33240 | CSTF2 | S518 | ochoa | Cleavage stimulation factor subunit 2 (CF-1 64 kDa subunit) (Cleavage stimulation factor 64 kDa subunit) (CSTF 64 kDa subunit) (CstF-64) | One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs. {ECO:0000269|PubMed:32816001, ECO:0000269|PubMed:9199325}. |
| P34932 | HSPA4 | S414 | ochoa | Heat shock 70 kDa protein 4 (HSP70RY) (Heat shock 70-related protein APG-2) (Heat shock protein family H member 2) | None |
| P34932 | HSPA4 | S556 | ochoa | Heat shock 70 kDa protein 4 (HSP70RY) (Heat shock 70-related protein APG-2) (Heat shock protein family H member 2) | None |
| P35250 | RFC2 | S30 | ochoa | Replication factor C subunit 2 (Activator 1 40 kDa subunit) (A1 40 kDa subunit) (Activator 1 subunit 2) (Replication factor C 40 kDa subunit) (RF-C 40 kDa subunit) (RFC40) | Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA (PubMed:9488738). This subunit binds ATP (By similarity). {ECO:0000250, ECO:0000269|PubMed:9488738}. |
| P35348 | ADRA1A | S246 | psp | Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P35348 | ADRA1A | S381 | psp | Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P35520 | CBS | S27 | ochoa | Cystathionine beta-synthase (EC 4.2.1.22) (Beta-thionase) (Serine sulfhydrase) | Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (PubMed:20506325, PubMed:23974653, PubMed:23981774). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (By similarity). {ECO:0000250|UniProtKB:P32232, ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774}. |
| P35568 | IRS1 | S323 | ochoa|psp | Insulin receptor substrate 1 (IRS-1) | Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:11171109, PubMed:8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}. |
| P35568 | IRS1 | S629 | ochoa|psp | Insulin receptor substrate 1 (IRS-1) | Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:11171109, PubMed:8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}. |
| P35680 | HNF1B | S52 | ochoa | Hepatocyte nuclear factor 1-beta (HNF-1-beta) (HNF-1B) (Homeoprotein LFB3) (Transcription factor 2) (TCF-2) (Variant hepatic nuclear factor 1) (vHNF1) | Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:17924661, PubMed:7900999). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity). Transcriptional activity is increased by coactivator PCBD1 (PubMed:24204001). {ECO:0000250|UniProtKB:Q03365, ECO:0000269|PubMed:17924661, ECO:0000269|PubMed:24204001, ECO:0000269|PubMed:7900999}. |
| P36382 | GJA5 | S120 | ochoa | Gap junction alpha-5 protein (Connexin-40) (Cx40) | One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. |
| P36897 | TGFBR1 | S189 | psp | TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I) | Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis (PubMed:33914044). The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:33914044, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}. |
| P36956 | SREBF1 | S448 | ochoa | Sterol regulatory element-binding protein 1 (SREBP-1) (Class D basic helix-loop-helix protein 1) (bHLHd1) (Sterol regulatory element-binding transcription factor 1) [Cleaved into: Processed sterol regulatory element-binding protein 1 (Transcription factor SREBF1)] | [Sterol regulatory element-binding protein 1]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:32322062}.; FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:12177166, PubMed:32322062, PubMed:8402897). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:12177166, PubMed:8402897). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:12177166, PubMed:32322062, PubMed:8402897). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8402897}.; FUNCTION: [Isoform SREBP-1A]: Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166, PubMed:32497488). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32497488}.; FUNCTION: [Isoform SREBP-1C]: Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166}.; FUNCTION: [Isoform SREBP-1aDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}.; FUNCTION: [Isoform SREBP-1cDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}. |
| P37275 | ZEB1 | S693 | ochoa | Zinc finger E-box-binding homeobox 1 (NIL-2-A zinc finger protein) (Negative regulator of IL2) (Transcription factor 8) (TCF-8) | Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (By similarity). {ECO:0000250|UniProtKB:Q64318, ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. |
| P38159 | RBMX | S307 | ochoa | RNA-binding motif protein, X chromosome (Glycoprotein p43) (Heterogeneous nuclear ribonucleoprotein G) (hnRNP G) [Cleaved into: RNA-binding motif protein, X chromosome, N-terminally processed] | RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Also plays a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:12761049, ECO:0000269|PubMed:16707624, ECO:0000269|PubMed:18445477, ECO:0000269|PubMed:18541147, ECO:0000269|PubMed:19282290, ECO:0000269|PubMed:21327109}. |
| P38398 | BRCA1 | S708 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P39880 | CUX1 | S1312 | ochoa | Homeobox protein cut-like 1 (CCAAT displacement protein) (CDP) (CDP/Cux p200) (Homeobox protein cux-1) [Cleaved into: CDP/Cux p110] | Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}. |
| P40818 | USP8 | S599 | ochoa | Ubiquitin carboxyl-terminal hydrolase 8 (EC 3.4.19.12) (Deubiquitinating enzyme 8) (Ubiquitin isopeptidase Y) (hUBPy) (Ubiquitin thioesterase 8) (Ubiquitin-specific-processing protease 8) | Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (PubMed:27302062). {ECO:0000269|PubMed:16520378, ECO:0000269|PubMed:17711858, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:27302062, ECO:0000269|PubMed:9628861}. |
| P40926 | MDH2 | S246 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P41231 | P2RY2 | S355 | ochoa | P2Y purinoceptor 2 (P2Y2) (ATP receptor) (P2U purinoceptor 1) (P2U1) (P2U receptor 1) (Purinergic receptor) | Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. The affinity range is UTP = ATP > ATP-gamma-S >> 2-methylthio-ATP = ADP. |
| P41743 | PRKCI | S19 | ochoa | Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) | Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}. |
| P42285 | MTREX | S40 | ochoa | Exosome RNA helicase MTR4 (EC 3.6.4.13) (ATP-dependent RNA helicase DOB1) (ATP-dependent RNA helicase SKIV2L2) (Superkiller viralicidic activity 2-like 2) (TRAMP-like complex helicase) | Catalyzes the ATP-dependent unwinding of RNA duplexes with a single-stranded 3' RNA extension (PubMed:27871484, PubMed:29844170, PubMed:29906447). Central subunit of many protein complexes, namely TRAMP-like, nuclear exosome targeting (NEXT) and poly(A) tail exosome targeting (PAXT) (PubMed:21855801, PubMed:27871484, PubMed:29844170). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484, PubMed:29844170). PAXT directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor ZCCHC8, which links to RNA-binding protein adapters (PubMed:27871484). Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA (PubMed:17412707, PubMed:29107693). May be involved in pre-mRNA splicing. In the context of NEXT complex can also in vitro unwind DNA:RNA heteroduplexes with a 3' poly (A) RNA tracking strand (PubMed:29844170). Can promote unwinding and degradation of structured RNA substrates when associated with the nuclear exosome and its cofactors. Can displace a DNA strand while translocating on RNA to ultimately degrade the RNA within a DNA/RNA heteroduplex (PubMed:29906447). Plays a role in DNA damage response (PubMed:29902117). {ECO:0000269|PubMed:17412707, ECO:0000269|PubMed:21855801, ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:29107693, ECO:0000269|PubMed:29844170, ECO:0000269|PubMed:29902117, ECO:0000269|PubMed:29906447}. |
| P42574 | CASP3 | S24 | ochoa | Caspase-3 (CASP-3) (EC 3.4.22.56) (Apopain) (Cysteine protease CPP32) (CPP-32) (Protein Yama) (SREBP cleavage activity 1) (SCA-1) [Cleaved into: Caspase-3 subunit p17; Caspase-3 subunit p12] | Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:7596430). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond (PubMed:10497198, PubMed:16374543, PubMed:7596430, PubMed:7774019). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively) (PubMed:7596430). Cleaves and inactivates interleukin-18 (IL18) (PubMed:37993714, PubMed:9334240). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (PubMed:35338844, PubMed:35446120). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106). {ECO:0000250|UniProtKB:Q60431, ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:16374543, ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:23152800, ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23845944, ECO:0000269|PubMed:30878284, ECO:0000269|PubMed:33725486, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106, ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:7596430, ECO:0000269|PubMed:7774019, ECO:0000269|PubMed:8696339, ECO:0000269|PubMed:9334240}. |
| P42858 | HTT | S419 | ochoa|psp | Huntingtin (Huntington disease protein) (HD protein) [Cleaved into: Huntingtin, myristoylated N-terminal fragment] | [Huntingtin]: May play a role in microtubule-mediated transport or vesicle function.; FUNCTION: [Huntingtin, myristoylated N-terminal fragment]: Promotes the formation of autophagic vesicles. {ECO:0000269|PubMed:24459296}. |
| P43121 | MCAM | S627 | ochoa | Cell surface glycoprotein MUC18 (Cell surface glycoprotein P1H12) (Melanoma cell adhesion molecule) (Melanoma-associated antigen A32) (Melanoma-associated antigen MUC18) (S-endo 1 endothelial-associated antigen) (CD antigen CD146) | Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as a surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration. {ECO:0000269|PubMed:11036077, ECO:0000269|PubMed:8292890}. |
| P43243 | MATR3 | S206 | ochoa | Matrin-3 | May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}. |
| P43243 | MATR3 | S615 | ochoa | Matrin-3 | May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}. |
| P43354 | NR4A2 | S256 | ochoa | Nuclear receptor subfamily 4 group A member 2 (Immediate-early response protein NOT) (Orphan nuclear receptor NURR1) (Transcriptionally-inducible nuclear receptor) | Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development (PubMed:15716272, PubMed:17184956). It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity). {ECO:0000250|UniProtKB:Q06219, ECO:0000269|PubMed:15716272, ECO:0000269|PubMed:17184956}. |
| P43364 | MAGEA11 | S199 | psp | Melanoma-associated antigen 11 (Cancer/testis antigen 1.11) (CT1.11) (MAGE-11 antigen) | Acts as androgen receptor coregulator that increases androgen receptor activity by modulating the receptors interdomain interaction. May play a role in embryonal development and tumor transformation or aspects of tumor progression. {ECO:0000269|PubMed:15684378}. |
| P45974 | USP5 | S710 | ochoa | Ubiquitin carboxyl-terminal hydrolase 5 (EC 3.4.19.12) (Deubiquitinating enzyme 5) (Isopeptidase T) (Ubiquitin thioesterase 5) (Ubiquitin-specific-processing protease 5) | Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter (PubMed:26912724). Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains (PubMed:29567855). Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein (PubMed:37534934). Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1 (PubMed:37208329). Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels (PubMed:37607937). Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3 (PubMed:39761299). Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4 (PubMed:39032648). Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination (PubMed:39900921). May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity). {ECO:0000250|UniProtKB:P56399, ECO:0000269|PubMed:19098288, ECO:0000269|PubMed:26912724, ECO:0000269|PubMed:29567855, ECO:0000269|PubMed:37208329, ECO:0000269|PubMed:37534934, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:39761299, ECO:0000269|PubMed:39900921}. |
| P46013 | MKI67 | S299 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S425 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2901 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46527 | CDKN1B | S178 | ochoa|psp | Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1) | Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. {ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:28666995}. |
| P46821 | MAP1B | S1190 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P46821 | MAP1B | S1330 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P46821 | MAP1B | S1406 | ochoa | Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] | Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}. |
| P47712 | PLA2G4A | S454 | ochoa|psp | Cytosolic phospholipase A2 (cPLA2) (Phospholipase A2 group IVA) [Includes: Phospholipase A2 (EC 3.1.1.4) (Phosphatidylcholine 2-acylhydrolase); Lysophospholipase (EC 3.1.1.5)] | Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891). {ECO:0000250|UniProtKB:P47713, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:12672805, ECO:0000269|PubMed:14709560, ECO:0000269|PubMed:16617059, ECO:0000269|PubMed:17472963, ECO:0000269|PubMed:18451993, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7794891, ECO:0000269|PubMed:8619991, ECO:0000269|PubMed:8702602, ECO:0000269|PubMed:9425121}. |
| P48163 | ME1 | S219 | ochoa | NADP-dependent malic enzyme (NADP-ME) (EC 1.1.1.40) (Malic enzyme 1) | Catalyzes the oxidative decarboxylation of (S)-malate in the presence of NADP(+) and divalent metal ions, and decarboxylation of oxaloacetate. {ECO:0000269|PubMed:7622060, ECO:0000269|PubMed:7757881, ECO:0000269|PubMed:8187880, ECO:0000269|PubMed:8804575}. |
| P48382 | RFX5 | S476 | ochoa | DNA-binding protein RFX5 (Regulatory factor X 5) | Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters. |
| P48382 | RFX5 | S505 | ochoa | DNA-binding protein RFX5 (Regulatory factor X 5) | Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters. |
| P48444 | ARCN1 | S188 | ochoa | Coatomer subunit delta (Archain) (Delta-coat protein) (Delta-COP) | Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| P48444 | ARCN1 | S195 | ochoa | Coatomer subunit delta (Archain) (Delta-coat protein) (Delta-COP) | Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| P48634 | PRRC2A | S908 | ochoa | Protein PRRC2A (HLA-B-associated transcript 2) (Large proline-rich protein BAT2) (Proline-rich and coiled-coil-containing protein 2A) (Protein G2) | May play a role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:14667819}. |
| P48634 | PRRC2A | S932 | ochoa | Protein PRRC2A (HLA-B-associated transcript 2) (Large proline-rich protein BAT2) (Proline-rich and coiled-coil-containing protein 2A) (Protein G2) | May play a role in the regulation of pre-mRNA splicing. {ECO:0000269|PubMed:14667819}. |
| P48681 | NES | S346 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P48681 | NES | S487 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P48681 | NES | S1445 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P48681 | NES | S1585 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P49023 | PXN | S533 | ochoa | Paxillin | Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion. {ECO:0000269|PubMed:25015296}. |
| P49069 | CAMLG | S20 | ochoa | Guided entry of tail-anchored proteins factor CAMLG (Calcium signal-modulating cyclophilin ligand) | Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (PubMed:23041287, PubMed:24392163, PubMed:27226539). Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (PubMed:23041287, PubMed:24392163, PubMed:27226539). Required for the stability of GET1 (PubMed:32187542). Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium (PubMed:7522304). Essential for the survival of peripheral follicular B cells (By similarity). {ECO:0000250|UniProtKB:P49070, ECO:0000269|PubMed:23041287, ECO:0000269|PubMed:24392163, ECO:0000269|PubMed:27226539, ECO:0000269|PubMed:32187542, ECO:0000269|PubMed:7522304}. |
| P49069 | CAMLG | S148 | ochoa | Guided entry of tail-anchored proteins factor CAMLG (Calcium signal-modulating cyclophilin ligand) | Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (PubMed:23041287, PubMed:24392163, PubMed:27226539). Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (PubMed:23041287, PubMed:24392163, PubMed:27226539). Required for the stability of GET1 (PubMed:32187542). Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium (PubMed:7522304). Essential for the survival of peripheral follicular B cells (By similarity). {ECO:0000250|UniProtKB:P49070, ECO:0000269|PubMed:23041287, ECO:0000269|PubMed:24392163, ECO:0000269|PubMed:27226539, ECO:0000269|PubMed:32187542, ECO:0000269|PubMed:7522304}. |
| P49247 | RPIA | S104 | ochoa | Ribose-5-phosphate isomerase (EC 5.3.1.6) (Phosphoriboisomerase) | Catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate and participates in the first step of the non-oxidative branch of the pentose phosphate pathway. {ECO:0000269|PubMed:14988808}. |
| P49321 | NASP | S689 | ochoa | Nuclear autoantigenic sperm protein (NASP) | Component of the histone chaperone network (PubMed:22195965). Binds and stabilizes histone H3-H4 not bound to chromatin to maintain a soluble reservoir and modulate degradation by chaperone-mediated autophagy (PubMed:22195965). Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. {ECO:0000250|UniProtKB:Q99MD9, ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 1]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 2]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}. |
| P49411 | TUFM | S222 | psp | Elongation factor Tu, mitochondrial (EF-Tu) (EC 3.6.5.3) (P43) | GTP hydrolase that promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. Also plays a role in the regulation of autophagy and innate immunity. Recruits ATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint of the RIGI-MAVS pathway. In turn, inhibits RLR-mediated type I interferon while promoting autophagy. {ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:28407488}. |
| P49448 | GLUD2 | S128 | ochoa | Glutamate dehydrogenase 2, mitochondrial (GDH 2) (EC 1.4.1.3) | Important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission. |
| P49674 | CSNK1E | S323 | ochoa|psp | Casein kinase I isoform epsilon (CKI-epsilon) (CKIe) (EC 2.7.11.1) | Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (Probable). Participates in Wnt signaling (PubMed:12556519, PubMed:23413191). Phosphorylates DVL1 (PubMed:12556519). Phosphorylates DVL2 (PubMed:23413191). Phosphorylates NEDD9/HEF1 (By similarity). Central component of the circadian clock (PubMed:16790549). In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:15917222, PubMed:16790549). Controls PER1 and PER2 nuclear transport and degradation (By similarity). Inhibits cytokine-induced granuloytic differentiation (PubMed:15070676). {ECO:0000250|UniProtKB:Q9JMK2, ECO:0000269|PubMed:12556519, ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:23413191, ECO:0000305|PubMed:7797465}. |
| P49736 | MCM2 | S700 | ochoa | DNA replication licensing factor MCM2 (EC 3.6.4.12) (Minichromosome maintenance protein 2 homolog) (Nuclear protein BM28) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (PubMed:8175912). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (PubMed:26196677). {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:8175912}. |
| P49759 | CLK1 | S328 | ochoa | Dual specificity protein kinase CLK1 (EC 2.7.12.1) (CDC-like kinase 1) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1 (PubMed:10480872, PubMed:19168442). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (PubMed:19168442). {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442}. |
| P49773 | HINT1 | S102 | ochoa | Adenosine 5'-monophosphoramidase HINT1 (EC 3.9.1.-) (Desumoylating isopeptidase HINT1) (EC 3.4.22.-) (Histidine triad nucleotide-binding protein 1) (Protein kinase C inhibitor 1) (Protein kinase C-interacting protein 1) (PKCI-1) | Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:15703176, PubMed:16835243, PubMed:17217311, PubMed:17337452, PubMed:22329685, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367). Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176, PubMed:16835243). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester (PubMed:15703176, PubMed:17337452, PubMed:22329685). Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17217311, PubMed:17337452, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367). Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide (PubMed:30772266). In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1 (PubMed:16014379, PubMed:22647378). Modulates p53/TP53 levels and p53/TP53-mediated apoptosis (PubMed:16835243). Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177). Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17 (PubMed:31088288). Deconjugates SUMO1 from RANGAP1 (By similarity). {ECO:0000250|UniProtKB:P80912, ECO:0000269|PubMed:15703176, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:17217311, ECO:0000269|PubMed:17337452, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:22329685, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:23614568, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:30772266, ECO:0000269|PubMed:31088288, ECO:0000269|PubMed:31990367}. |
| P49792 | RANBP2 | S1117 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S1160 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S1835 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S2199 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S2693 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S2844 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49916 | LIG3 | S847 | ochoa | DNA ligase 3 (EC 6.5.1.1) (DNA ligase III) (Polydeoxyribonucleotide synthase [ATP] 3) | Isoform 3 functions as a heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as a DNA ligase in mitochondrial base-excision DNA repair (PubMed:10207110, PubMed:24674627). {ECO:0000269|PubMed:10207110, ECO:0000269|PubMed:24674627}. |
| P49959 | MRE11 | S268 | ochoa | Double-strand break repair protein MRE11 (EC 3.1.-.-) (Meiotic recombination 11 homolog 1) (MRE11 homolog 1) (Meiotic recombination 11 homolog A) (MRE11 homolog A) | Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:11741547, PubMed:14657032, PubMed:22078559, PubMed:23080121, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:28867292, PubMed:29670289, PubMed:30464262, PubMed:30612738, PubMed:31353207, PubMed:37696958, PubMed:38128537, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:24316220, PubMed:28867292, PubMed:31353207, PubMed:38128537). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:24316220, PubMed:27889449, PubMed:28867292, PubMed:36050397, PubMed:38128537). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:11741547, PubMed:22078559, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:29670289, PubMed:31353207, PubMed:36563124, PubMed:9590181, PubMed:9651580, PubMed:9705271). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (PubMed:24316220). It then generates a single-stranded DNA gap via 3' to 5' exonucleolytic degradation to create entry sites for EXO1- and DNA2-mediated 5' to 3' long-range resection, which is required for single-strand invasion and recombination (PubMed:24316220, PubMed:28867292). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 endonuclease activity is also enhanced by AGER/RAGE (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:14657032, PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). The MRN complex is involved in the activation of the cGAS-STING pathway induced by DNA damage during tumorigenesis: the MRN complex acts by displacing CGAS from nucleosome sequestration, thereby activating it (By similarity). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q61216, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:14657032, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:22078559, ECO:0000269|PubMed:23080121, ECO:0000269|PubMed:24316220, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:29670289, ECO:0000269|PubMed:30464262, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:31353207, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:36050397, ECO:0000269|PubMed:36563124, ECO:0000269|PubMed:37696958, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}.; FUNCTION: MRE11 contains two DNA-binding domains (DBDs), enabling it to bind both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). {ECO:0000305}. |
| P50548 | ERF | S185 | ochoa | ETS domain-containing transcription factor ERF (Ets2 repressor factor) (PE-2) | Potent transcriptional repressor that binds to the H1 element of the Ets2 promoter. May regulate other genes involved in cellular proliferation. Required for extraembryonic ectoderm differentiation, ectoplacental cone cavity closure, and chorioallantoic attachment (By similarity). May be important for regulating trophoblast stem cell differentiation (By similarity). {ECO:0000250}. |
| P50747 | HLCS | S79 | ochoa | Biotin--protein ligase (EC 6.3.4.-) (Biotin apo-protein ligase) [Includes: Biotin--[methylmalonyl-CoA-carboxytransferase] ligase (EC 6.3.4.9); Biotin--[propionyl-CoA-carboxylase [ATP-hydrolyzing]] ligase (EC 6.3.4.10) (Holocarboxylase synthetase) (HCS); Biotin--[methylcrotonoyl-CoA-carboxylase] ligase (EC 6.3.4.11); Biotin--[acetyl-CoA-carboxylase] ligase (EC 6.3.4.15)] | Biotin--protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase. {ECO:0000269|PubMed:10590022, ECO:0000269|PubMed:7753853, ECO:0000269|PubMed:7842009}. |
| P50748 | KNTC1 | S1034 | ochoa | Kinetochore-associated protein 1 (Rough deal homolog) (HsROD) (Rod) (hRod) | Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores (PubMed:11146660, PubMed:11590237, PubMed:15824131). Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex. {ECO:0000269|PubMed:11146660, ECO:0000269|PubMed:11590237, ECO:0000269|PubMed:15824131, ECO:0000305}. |
| P50993 | ATP1A2 | S665 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-2) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P51608 | MECP2 | S274 | ochoa | Methyl-CpG-binding protein 2 (MeCp-2 protein) (MeCp2) | Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC). {ECO:0000250|UniProtKB:Q9Z2D6}. |
| P51659 | HSD17B4 | S198 | ochoa | Peroxisomal multifunctional enzyme type 2 (MFE-2) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) (D-bifunctional protein) (DBP) (Multifunctional protein 2) (MFP-2) (Short chain dehydrogenase/reductase family 8C member 1) [Cleaved into: (3R)-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.n12); Enoyl-CoA hydratase 2 (EC 4.2.1.107) (EC 4.2.1.119) (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase)] | Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway. Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates. {ECO:0000269|PubMed:10671535, ECO:0000269|PubMed:15060085, ECO:0000269|PubMed:8902629, ECO:0000269|PubMed:9089413}. |
| P51659 | HSD17B4 | S294 | ochoa | Peroxisomal multifunctional enzyme type 2 (MFE-2) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) (D-bifunctional protein) (DBP) (Multifunctional protein 2) (MFP-2) (Short chain dehydrogenase/reductase family 8C member 1) [Cleaved into: (3R)-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.n12); Enoyl-CoA hydratase 2 (EC 4.2.1.107) (EC 4.2.1.119) (3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase)] | Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway. Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates. {ECO:0000269|PubMed:10671535, ECO:0000269|PubMed:15060085, ECO:0000269|PubMed:8902629, ECO:0000269|PubMed:9089413}. |
| P51784 | USP11 | S942 | ochoa | Ubiquitin carboxyl-terminal hydrolase 11 (EC 3.4.19.12) (Deubiquitinating enzyme 11) (Ubiquitin thioesterase 11) (Ubiquitin-specific-processing protease 11) | Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains (PubMed:12084015, PubMed:15314155, PubMed:17897950, PubMed:19874889, PubMed:20233726, PubMed:24724799, PubMed:28992046). Inhibits the degradation of target proteins by the proteasome (PubMed:12084015). Cleaves preferentially 'Lys-6' and 'Lys-63'-linked ubiquitin chains. Has lower activity with 'Lys-11' and 'Lys-33'-linked ubiquitin chains, and extremely low activity with 'Lys-27', 'Lys-29' and 'Lys-48'-linked ubiquitin chains (in vitro) (PubMed:24724799). Plays a role in the regulation of pathways leading to NF-kappa-B activation (PubMed:17897950, PubMed:19874889). Plays a role in the regulation of DNA repair after double-stranded DNA breaks (PubMed:15314155, PubMed:20233726). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). Promotes cell proliferation by deubiquitinating phosphorylated E2F1 (PubMed:28992046). {ECO:0000269|PubMed:15314155, ECO:0000269|PubMed:17897950, ECO:0000269|PubMed:18408009, ECO:0000269|PubMed:19874889, ECO:0000269|PubMed:20233726, ECO:0000269|PubMed:24724799, ECO:0000269|PubMed:28992046}. |
| P51787 | KCNQ1 | S27 | psp | Potassium voltage-gated channel subfamily KQT member 1 (IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1) (KQT-like 1) (Voltage-gated potassium channel subunit Kv7.1) | Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Also promotes a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation, participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.; FUNCTION: [Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269|PubMed:9305853}. |
| P52272 | HNRNPM | S204 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52272 | HNRNPM | S452 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52272 | HNRNPM | S481 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52272 | HNRNPM | S513 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52272 | HNRNPM | S637 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P52565 | ARHGDIA | S148 | ochoa | Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) | Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}. |
| P52565 | ARHGDIA | S174 | psp | Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) | Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}. |
| P52566 | ARHGDIB | S145 | ochoa | Rho GDP-dissociation inhibitor 2 (Rho GDI 2) (Ly-GDI) (Rho-GDI beta) | Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them (PubMed:7512369, PubMed:8356058). Regulates reorganization of the actin cytoskeleton mediated by Rho family members (PubMed:8262133). {ECO:0000269|PubMed:7512369, ECO:0000269|PubMed:8262133, ECO:0000269|PubMed:8356058}. |
| P53367 | ARFIP1 | S93 | ochoa | Arfaptin-1 (ADP-ribosylation factor-interacting protein 1) | Plays a role in controlling biogenesis of secretory granules at the trans-Golgi network (PubMed:22981988). Mechanistically, binds ARF-GTP at the neck of a growing secretory granule precursor and forms a protective scaffold (PubMed:22981988, PubMed:9038142). Once the granule precursor has been completely loaded, active PRKD1 phosphorylates ARFIP1 and releases it from ARFs (PubMed:22981988). In turn, ARFs induce fission (PubMed:22981988). Through this mechanism, ensures proper secretory granule formation at the Golgi of pancreatic beta cells (PubMed:22981988). {ECO:0000269|PubMed:22981988, ECO:0000269|PubMed:9038142}. |
| P53396 | ACLY | S444 | ochoa | ATP-citrate synthase (EC 2.3.3.8) (ATP-citrate (pro-S-)-lyase) (ACL) (Citrate cleavage enzyme) | Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism. {ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:39881208, ECO:0000269|PubMed:9116495}. |
| P53814 | SMTN | S779 | ochoa | Smoothelin | Structural protein of the cytoskeleton. |
| P54821 | PRRX1 | S74 | ochoa | Paired mesoderm homeobox protein 1 (Homeobox protein PHOX1) (Paired-related homeobox protein 1) (PRX-1) | Master transcription factor of stromal fibroblasts for myofibroblastic lineage progression. Orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-beta signaling by remodeling a super-enhancer landscape. Through this function, plays an essential role in wound healing process (PubMed:35589735). Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer (By similarity). May play a role in homeostasis and regeneration of bone, white adipose tissue and derm (By similarity). {ECO:0000250|UniProtKB:P63013, ECO:0000269|PubMed:35589735}.; FUNCTION: [Isoform 1]: Transcriptional activator, when transfected in fibroblastic or myoblastic cell lines. This activity may be masked by the C-terminal OAR domain. {ECO:0000250|UniProtKB:P63013}.; FUNCTION: [Isoform 2]: Transcriptional repressor, when transfected in fibroblastic or myoblastic cell lines. {ECO:0000250|UniProtKB:P63013}. |
| P54886 | ALDH18A1 | S79 | ochoa | Delta-1-pyrroline-5-carboxylate synthase (P5CS) (Aldehyde dehydrogenase family 18 member A1) [Includes: Glutamate 5-kinase (GK) (EC 2.7.2.11) (Gamma-glutamyl kinase); Gamma-glutamyl phosphate reductase (GPR) (EC 1.2.1.41) (Glutamate-5-semialdehyde dehydrogenase) (Glutamyl-gamma-semialdehyde dehydrogenase)] | Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine. {ECO:0000269|PubMed:10037775, ECO:0000269|PubMed:11092761, ECO:0000269|PubMed:26297558, ECO:0000269|PubMed:26320891, ECO:0000269|PubMed:39506109}. |
| P55042 | RRAD | S85 | ochoa | GTP-binding protein RAD (RAD1) (Ras associated with diabetes) | May regulate basal voltage-dependent L-type Ca(2+) currents and be required for beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (By similarity). May play an important role in cardiac antiarrhythmia via the strong suppression of voltage-gated L-type Ca(2+) currents (By similarity). Regulates voltage-dependent L-type calcium channel subunit alpha-1C trafficking to the cell membrane (By similarity). Inhibits cardiac hypertrophy through the calmodulin-dependent kinase II (CaMKII) pathway (PubMed:18056528). Inhibits phosphorylation and activation of CAMK2D (PubMed:18056528). {ECO:0000250|UniProtKB:O88667, ECO:0000269|PubMed:18056528}. |
| P55198 | MLLT6 | S435 | ochoa | Protein AF-17 (ALL1-fused gene from chromosome 17 protein) | None |
| P55201 | BRPF1 | S452 | ochoa | Peregrin (Bromodomain and PHD finger-containing protein 1) (Protein Br140) | Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:24065767, PubMed:27939640). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac) (PubMed:24065767). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (PubMed:18794358). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:27939640}. |
| P55201 | BRPF1 | S844 | ochoa | Peregrin (Bromodomain and PHD finger-containing protein 1) (Protein Br140) | Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:24065767, PubMed:27939640). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac) (PubMed:24065767). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (PubMed:18794358). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:27939640}. |
| P55210 | CASP7 | S239 | psp | Caspase-7 (CASP-7) (EC 3.4.22.60) (Apoptotic protease Mch-3) (CMH-1) (ICE-like apoptotic protease 3) (ICE-LAP3) [Cleaved into: Caspase-7 subunit p20; Caspase-7 subunit p11] | Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (PubMed:11257230, PubMed:11257231, PubMed:11701129, PubMed:15314233, PubMed:16916640, PubMed:17646170, PubMed:18723680, PubMed:19581639, PubMed:8521391, PubMed:8567622, PubMed:8576161, PubMed:9070923). Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences (PubMed:12824163, PubMed:15314233, PubMed:17697120, PubMed:19581639, PubMed:20566630, PubMed:23650375, PubMed:23897474, PubMed:27032039). Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (By similarity). Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and YY1 (PubMed:10497198, PubMed:16123041, PubMed:16374543, PubMed:16916640, PubMed:18723680, PubMed:20566630, PubMed:21555521, PubMed:22184066, PubMed:22451931, PubMed:27889207, PubMed:28863261, PubMed:31586028, PubMed:34156061, PubMed:35338844, PubMed:35446120). Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins (PubMed:18723680). Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair (PubMed:21157428). Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores (By similarity). Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores (By similarity). Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1 (PubMed:22464733). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (By similarity). Cleaves and activates sterol regulatory element binding proteins (SREBPs) (PubMed:8643593). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9 (By similarity). In case of infection, catalyzes cleavage of Kaposi sarcoma-associated herpesvirus protein ORF57, thereby preventing expression of viral lytic genes (PubMed:20159985). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106). {ECO:0000250|UniProtKB:P97864, ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:16374543, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17646170, ECO:0000269|PubMed:17697120, ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:20159985, ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:21157428, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:22184066, ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23897474, ECO:0000269|PubMed:27032039, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:28863261, ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106, ECO:0000269|PubMed:8521391, ECO:0000269|PubMed:8567622, ECO:0000269|PubMed:8576161, ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9070923}.; FUNCTION: [Isoform Beta]: Lacks enzymatic activity. {ECO:0000269|PubMed:8521391}. |
| P56693 | SOX10 | S40 | ochoa|psp | Transcription factor SOX-10 | Transcription factor that plays a central role in developing and mature glia (By similarity). Specifically activates expression of myelin genes, during oligodendrocyte (OL) maturation, such as DUSP15 and MYRF, thereby playing a central role in oligodendrocyte maturation and CNS myelination (By similarity). Once induced, MYRF cooperates with SOX10 to implement the myelination program (By similarity). Transcriptional activator of MITF, acting synergistically with PAX3 (PubMed:21965087). Transcriptional activator of MBP, via binding to the gene promoter (By similarity). {ECO:0000250|UniProtKB:O55170, ECO:0000250|UniProtKB:Q04888, ECO:0000269|PubMed:21965087}. |
| P57060 | RWDD2B | S178 | ochoa | RWD domain-containing protein 2B | None |
| P57764 | GSDMD | S181 | ochoa | Gasdermin-D (Gasdermin domain-containing protein 1) [Cleaved into: Gasdermin-D, N-terminal (GSDMD-NT) (hGSDMD-NTD); Gasdermin-D, C-terminal (GSDMD-CT) (hGSDMD-CTD); Gasdermin-D, p13 (Gasdermin-D, 13 kDa) (13 kDa GSDMD); Gasdermin-D, p40] | [Gasdermin-D]: Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:27281216). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-D, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:26375003, PubMed:26375259, PubMed:27281216). {ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:27281216}.; FUNCTION: [Gasdermin-D, N-terminal]: Promotes pyroptosis in response to microbial infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:27418190, PubMed:28392147, PubMed:32820063, PubMed:34289345, PubMed:38040708, PubMed:38530158, PubMed:38599239). Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1, CASP4 or CASP5 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, PubMed:27418190). After cleavage, moves to the plasma membrane where it strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine (PubMed:27281216, PubMed:29898893, PubMed:36227980). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukin-1 (IL1B and IL18) and triggering pyroptosis (PubMed:27281216, PubMed:27418190, PubMed:29898893, PubMed:33883744, PubMed:38040708, PubMed:38530158, PubMed:38599239). Gasdermin pores also allow the release of mature caspase-7 (CASP7) (By similarity). In some, but not all, cells types, pyroptosis is followed by pyroptotic cell death, which is caused by downstream activation of ninjurin-1 (NINJ1), which mediates membrane rupture (cytolysis) (PubMed:33472215, PubMed:37198476). Also forms pores in the mitochondrial membrane, resulting in release of mitochondrial DNA (mtDNA) into the cytosol (By similarity). Gasdermin-D, N-terminal released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity (PubMed:27281216). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (By similarity). Also active in response to MAP3K7/TAK1 inactivation by Yersinia toxin YopJ, which triggers cleavage by CASP8 and subsequent activation (By similarity). Required for mucosal tissue defense against enteric pathogens (By similarity). Activation of the non-canonical inflammasome in brain endothelial cells can lead to excessive pyroptosis, leading to blood-brain barrier breakdown (By similarity). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin (PubMed:27281216). Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27281216). {ECO:0000250|UniProtKB:Q9D8T2, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:26375259, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:27418190, ECO:0000269|PubMed:28392147, ECO:0000269|PubMed:29898893, ECO:0000269|PubMed:32820063, ECO:0000269|PubMed:33472215, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:36227980, ECO:0000269|PubMed:37198476, ECO:0000269|PubMed:38040708, ECO:0000269|PubMed:38530158, ECO:0000269|PubMed:38599239}.; FUNCTION: [Gasdermin-D, p13]: Transcription coactivator produced by the cleavage by CASP3 or CASP7 in the upper small intestine in response to dietary antigens (By similarity). Required to maintain food tolerance in small intestine: translocates to the nucleus and acts as a coactivator for STAT1 to induce the transcription of CIITA and MHC class II molecules, which in turn induce type 1 regulatory T (Tr1) cells in upper small intestine (By similarity). {ECO:0000250|UniProtKB:Q9D8T2}.; FUNCTION: [Gasdermin-D, p40]: Produced by the cleavage by papain allergen (PubMed:35794369). After cleavage, moves to the plasma membrane and homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the specific release of mature interleukin-33 (IL33), promoting type 2 inflammatory immune response (PubMed:35794369). {ECO:0000269|PubMed:35794369}. |
| P61006 | RAB8A | S185 | ochoa | Ras-related protein Rab-8A (EC 3.6.5.2) (Oncogene c-mel) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB8A is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297). Regulates the compacted morphology of the Golgi (PubMed:26209634). Together with MYO5B and RAB11A participates in epithelial cell polarization (PubMed:21282656). Also involved in membrane trafficking to the cilium and ciliogenesis (PubMed:21844891, PubMed:30398148, PubMed:20631154). Together with MICALL2, may also regulate adherens junction assembly (By similarity). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (PubMed:27103069). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433). Targeted to and stabilized on stressed lysosomes through LRRK2 phosphorylation (PubMed:30209220). Suppresses stress-induced lysosomal enlargement through EHBP1 and EHNP1L1 effector proteins (PubMed:30209220). {ECO:0000250|UniProtKB:P35280, ECO:0000250|UniProtKB:P55258, ECO:0000269|PubMed:20631154, ECO:0000269|PubMed:20890297, ECO:0000269|PubMed:21282656, ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:32344433}. |
| P61604 | HSPE1 | S51 | ochoa | 10 kDa heat shock protein, mitochondrial (Hsp10) (10 kDa chaperonin) (Chaperonin 10) (CPN10) (Early-pregnancy factor) (EPF) (Heat shock protein family E member 1) | Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131, PubMed:7912672). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000269|PubMed:7912672, ECO:0000305|PubMed:25918392}. |
| P61956 | SUMO2 | S28 | ochoa | Small ubiquitin-related modifier 2 (SUMO-2) (HSMT3) (SMT3 homolog 2) (SUMO-3) (Sentrin-2) (Ubiquitin-like protein SMT3B) (Smt3B) | Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2, CBX4 or ZNF451 (PubMed:26524494). This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins (PubMed:18408734, PubMed:18538659, PubMed:21965678, PubMed:9556629). Plays a role in the regulation of sumoylation status of SETX (PubMed:24105744). {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:26524494, ECO:0000269|PubMed:9556629}. |
| P61978 | HNRNPK | S379 | ochoa|psp | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P62857 | RPS28 | S23 | ochoa | Small ribosomal subunit protein eS28 (40S ribosomal protein S28) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:25957688). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:34516797}. |
| P62937 | PPIA | S147 | ochoa | Peptidyl-prolyl cis-trans isomerase A (PPIase A) (EC 5.2.1.8) (Cyclophilin A) (Cyclosporin A-binding protein) (Rotamase A) [Cleaved into: Peptidyl-prolyl cis-trans isomerase A, N-terminally processed] | Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.; FUNCTION: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.; FUNCTION: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}. |
| P62995 | TRA2B | S26 | ochoa | Transformer-2 protein homolog beta (TRA-2 beta) (TRA2-beta) (hTRA2-beta) (Splicing factor, arginine/serine-rich 10) (Transformer-2 protein homolog B) | Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. Can either activate or suppress exon inclusion. Acts additively with RBMX to promote exon 7 inclusion of the survival motor neuron SMN2. Activates the splicing of MAPT/Tau exon 10. Alters pre-mRNA splicing patterns by antagonizing the effects of splicing regulators, like RBMX. Binds to the AG-rich SE2 domain in the SMN exon 7 RNA. Binds to pre-mRNA. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:12761049, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:9546399}. |
| P67809 | YBX1 | S136 | ochoa | Y-box-binding protein 1 (YB-1) (CCAAT-binding transcription factor I subunit A) (CBF-A) (DNA-binding protein B) (DBPB) (Enhancer factor I subunit A) (EFI-A) (Nuclease-sensitive element-binding protein 1) (Y-box transcription factor) | DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:10817758, PubMed:11698476, PubMed:14718551, PubMed:18809583, PubMed:31358969, PubMed:8188694). Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (PubMed:19561594, PubMed:31358969). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (PubMed:10817758, PubMed:11698476, PubMed:31358969). Component of the CRD-mediated complex that promotes MYC mRNA stability (PubMed:19029303). Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs (PubMed:27559612, PubMed:29073095). Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (PubMed:28341602, PubMed:29073095). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (PubMed:29712925). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (PubMed:12604611). Binds to TSC22D1 transcripts, thereby inhibiting their translation and negatively regulating TGF-beta-mediated transcription of COL1A2 (By similarity). Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7' (PubMed:18809583). Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (PubMed:18809583, PubMed:8188694). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (PubMed:14718551). Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (PubMed:14718551). The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (PubMed:19483673). {ECO:0000250|UniProtKB:P62960, ECO:0000250|UniProtKB:Q28618, ECO:0000269|PubMed:10817758, ECO:0000269|PubMed:11698476, ECO:0000269|PubMed:12604611, ECO:0000269|PubMed:14718551, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19483673, ECO:0000269|PubMed:19561594, ECO:0000269|PubMed:27559612, ECO:0000269|PubMed:28341602, ECO:0000269|PubMed:29073095, ECO:0000269|PubMed:29712925, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:8188694}. |
| P78312 | FAM193A | S972 | ochoa | Protein FAM193A (Protein IT14) | None |
| P78332 | RBM6 | S240 | ochoa | RNA-binding protein 6 (Lung cancer antigen NY-LU-12) (Protein G16) (RNA-binding motif protein 6) (RNA-binding protein DEF-3) | Specifically binds poly(G) RNA homopolymers in vitro. |
| P78344 | EIF4G2 | S381 | ochoa | Eukaryotic translation initiation factor 4 gamma 2 (eIF-4-gamma 2) (eIF-4G 2) (eIF4G 2) (Death-associated protein 5) (DAP-5) (p97) | Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases. {ECO:0000269|PubMed:11511540, ECO:0000269|PubMed:11943866, ECO:0000269|PubMed:9032289, ECO:0000269|PubMed:9049310}. |
| P78347 | GTF2I | S214 | ochoa | General transcription factor II-I (GTFII-I) (TFII-I) (Bruton tyrosine kinase-associated protein 135) (BAP-135) (BTK-associated protein 135) (SRF-Phox1-interacting protein) (SPIN) (Williams-Beuren syndrome chromosomal region 6 protein) | Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C-FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box. Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation. {ECO:0000269|PubMed:10373551, ECO:0000269|PubMed:11373296, ECO:0000269|PubMed:16738337}. |
| P78411 | IRX5 | S246 | ochoa | Iroquois-class homeodomain protein IRX-5 (Homeodomain protein IRX-2A) (Homeodomain protein IRXB2) (Iroquois homeobox protein 5) | Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene. Required for retinal cone bipolar cell differentiation. May regulate contrast adaptation in the retina and control specific aspects of visual function in circuits of the mammalian retina (By similarity). Could be involved in the regulation of both the cell cycle and apoptosis in prostate cancer cells. Involved in craniofacial and gonadal development. Modulates the migration of progenitor cell populations in branchial arches and gonads by repressing CXCL12. {ECO:0000250, ECO:0000269|PubMed:22581230}. |
| P78417 | GSTO1 | S129 | ochoa | Glutathione S-transferase omega-1 (GSTO-1) (EC 2.5.1.18) (Glutathione S-transferase omega 1-1) (GSTO 1-1) (Glutathione-dependent dehydroascorbate reductase) (EC 1.8.5.1) (Monomethylarsonic acid reductase) (MMA(V) reductase) (EC 1.20.4.2) (S-(Phenacyl)glutathione reductase) (SPG-R) | Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Also has glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. {ECO:0000269|PubMed:10783391, ECO:0000269|PubMed:11511179, ECO:0000269|PubMed:17226937, ECO:0000269|PubMed:18028863, ECO:0000269|PubMed:21106529}. |
| P78524 | DENND2B | S357 | ochoa | DENN domain-containing protein 2B (HeLa tumor suppression 1) (Suppression of tumorigenicity 5 protein) | [Isoform 1]: May be involved in cytoskeletal organization and tumorogenicity. Seems to be involved in a signaling transduction pathway leading to activation of MAPK1/ERK2. Plays a role in EGFR trafficking from recycling endosomes back to the cell membrane (PubMed:29030480). {ECO:0000269|PubMed:29030480, ECO:0000269|PubMed:9632734}.; FUNCTION: [Isoform 2]: Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}.; FUNCTION: [Isoform 3]: May block ERK2 activation stimulated by ABL1 (Probable). May alter cell morphology and cell growth (Probable). {ECO:0000305|PubMed:10229203, ECO:0000305|PubMed:9632734}. |
| P78559 | MAP1A | S2259 | ochoa | Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Cleaved into: MAP1A heavy chain; MAP1 light chain LC2] | Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. |
| P78559 | MAP1A | S2419 | ochoa | Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Cleaved into: MAP1A heavy chain; MAP1 light chain LC2] | Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. |
| P78563 | ADARB1 | S31 | ochoa | Double-stranded RNA-specific editase 1 (EC 3.5.4.37) (RNA-editing deaminase 1) (RNA-editing enzyme 1) (dsRNA adenosine deaminase) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis. {ECO:0000269|PubMed:18178553, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159}.; FUNCTION: [Isoform 1]: Has a lower catalytic activity than isoform 2. {ECO:0000269|PubMed:9149227}.; FUNCTION: [Isoform 2]: Has a higher catalytic activity than isoform 1. {ECO:0000269|PubMed:9149227}. |
| P98160 | HSPG2 | S4277 | ochoa | Basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) (Perlecan) (PLC) [Cleaved into: Endorepellin; LG3 peptide] | Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development.; FUNCTION: [Endorepellin]: Anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6.; FUNCTION: [LG3 peptide]: Has anti-angiogenic properties that require binding of calcium ions for full activity. |
| P98160 | HSPG2 | S4306 | ochoa | Basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) (Perlecan) (PLC) [Cleaved into: Endorepellin; LG3 peptide] | Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development.; FUNCTION: [Endorepellin]: Anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6.; FUNCTION: [LG3 peptide]: Has anti-angiogenic properties that require binding of calcium ions for full activity. |
| P98161 | PKD1 | S4169 | psp | Polycystin-1 (PC1) (Autosomal dominant polycystic kidney disease 1 protein) | Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both PKD1 and PKD2 are required for channel activity (PubMed:27214281). Involved in renal tubulogenesis (PubMed:12482949). Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). Acts as a regulator of cilium length, together with PKD2 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling (By similarity). The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions. Likely to be involved with polycystin-1-interacting protein 1 in the detection, sequestration and exocytosis of senescent mitochondria (PubMed:37681898). {ECO:0000250|UniProtKB:O08852, ECO:0000269|PubMed:12482949, ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:37681898}. |
| P98172 | EFNB1 | S292 | ochoa | Ephrin-B1 (EFL-3) (ELK ligand) (ELK-L) (EPH-related receptor tyrosine kinase ligand 2) (LERK-2) [Cleaved into: Ephrin-B1 C-terminal fragment (Ephrin-B1 CTF); Ephrin-B1 intracellular domain (Ephrin-B1 ICD)] | Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development (PubMed:7973638, PubMed:8070404). Binding to Eph receptors residing on adjacent cells leads to contact-dependent bidirectional signaling into neighboring cells (PubMed:7973638, PubMed:8070404). Shows high affinity for the receptor tyrosine kinase EPHB1/ELK (PubMed:7973638, PubMed:8070404). Can also bind EPHB2 and EPHB3 (PubMed:8070404). Binds to, and induces collapse of, commissural axons/growth cones in vitro (By similarity). May play a role in constraining the orientation of longitudinally projecting axons (By similarity). {ECO:0000250|UniProtKB:P52795, ECO:0000269|PubMed:7973638, ECO:0000269|PubMed:8070404}. |
| P98174 | FGD1 | S50 | ochoa | FYVE, RhoGEF and PH domain-containing protein 1 (Faciogenital dysplasia 1 protein) (Rho/Rac guanine nucleotide exchange factor FGD1) (Rho/Rac GEF) (Zinc finger FYVE domain-containing protein 3) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:8969170}. |
| P98175 | RBM10 | S50 | ochoa | RNA-binding protein 10 (G patch domain-containing protein 9) (RNA-binding motif protein 10) (RNA-binding protein S1-1) (S1-1) | Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). May be involved in post-transcriptional processing, most probably in mRNA splicing (PubMed:18315527). Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000250|UniProtKB:P70501, ECO:0000269|PubMed:18315527, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:28431233}. |
| Q00536 | CDK16 | S42 | ochoa | Cyclin-dependent kinase 16 (EC 2.7.11.22) (Cell division protein kinase 16) (PCTAIRE-motif protein kinase 1) (Serine/threonine-protein kinase PCTAIRE-1) | Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}. |
| Q00613 | HSF1 | S218 | ochoa | Heat shock factor protein 1 (HSF 1) (Heat shock transcription factor 1) (HSTF 1) | Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage (PubMed:11447121, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:18451878, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7760831, PubMed:8940068, PubMed:8946918, PubMed:9121459, PubMed:9341107, PubMed:9499401, PubMed:9535852, PubMed:9727490). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:11583998, PubMed:16278218, PubMed:9727490). Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes (PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7935471, PubMed:8455624, PubMed:8940068, PubMed:9499401, PubMed:9727490). Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival (PubMed:18451878). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock gene promoters (PubMed:25963659). Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 (PubMed:34723967). Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells (PubMed:9341107). Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic progression (PubMed:18794143). Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner (PubMed:26359349). Involved in stress-induced cancer cell proliferation in a IER5-dependent manner (PubMed:26754925). {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12659875, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:1871105, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:1986252, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26727489, ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:34723967, ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831, ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624, ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9341107, ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9535852, ECO:0000269|PubMed:9727490}.; FUNCTION: (Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300. {ECO:0000269|PubMed:27189267}. |
| Q01484 | ANK2 | S2642 | ochoa | Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) | Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:Q8C8R3, ECO:0000269|PubMed:12571597}. |
| Q01650 | SLC7A5 | S35 | ochoa | Large neutral amino acids transporter small subunit 1 (4F2 light chain) (4F2 LC) (4F2LC) (CD98 light chain) (Integral membrane protein E16) (E16) (L-type amino acid transporter 1) (hLAT1) (Solute carrier family 7 member 5) (y+ system cationic amino acid transporter) | The heterodimer with SLC3A2 functions as a sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine, isoleucine and alanine (PubMed:10049700, PubMed:10574970, PubMed:11557028, PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:15769744, PubMed:18262359, PubMed:25998567, PubMed:30867591, PubMed:9751058). The heterodimer with SLC3A2 mediates the uptake of L-DOPA (By similarity). Functions as an amino acid exchanger (PubMed:11557028, PubMed:12117417, PubMed:12225859, PubMed:30867591). May play a role in the transport of L-DOPA across the blood-brain barrier (By similarity). May act as the major transporter of tyrosine in fibroblasts (Probable). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier (By similarity). Can mediate the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane (PubMed:11564694). When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes (PubMed:12117417). Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane (PubMed:15769744). {ECO:0000250|UniProtKB:Q63016, ECO:0000250|UniProtKB:Q9Z127, ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:18262359, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:9751058, ECO:0000305|PubMed:18262359}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}. |
| Q02241 | KIF23 | S906 | ochoa | Kinesin-like protein KIF23 (Kinesin-like protein 5) (Mitotic kinesin-like protein 1) | Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Essential for cytokinesis in Rho-mediated signaling. Required for the localization of ECT2 to the central spindle. Plus-end-directed motor enzyme that moves antiparallel microtubules in vitro. {ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:22522702, ECO:0000269|PubMed:23570799}. |
| Q02487 | DSC2 | S864 | ochoa | Desmocollin-2 (Cadherin family member 2) (Desmocollin-3) (Desmosomal glycoprotein II) (Desmosomal glycoprotein III) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:33596089). Promotes timely incorporation of DSG2 into desmosome intercellular junctions and promotes interaction of desmosome cell junctions with intermediate filament cytokeratin, via modulation of DSP phosphorylation (PubMed:33596089). Plays an important role in desmosome-mediated maintenance of intestinal epithelial cell intercellular adhesion strength and barrier function (PubMed:33596089). Positively regulates wound healing of intestinal mucosa via promotion of epithelial cell migration, and also plays a role in mechanotransduction of force between intestinal epithelial cells and extracellular matrix (PubMed:31967937). May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. May promote p38MAPK signaling activation that facilitates keratinocyte migration (By similarity). {ECO:0000250|UniProtKB:P55292, ECO:0000269|PubMed:31967937, ECO:0000269|PubMed:33596089}. |
| Q02790 | FKBP4 | S229 | ochoa | Peptidyl-prolyl cis-trans isomerase FKBP4 (PPIase FKBP4) (EC 5.2.1.8) (51 kDa FK506-binding protein) (FKBP51) (52 kDa FK506-binding protein) (52 kDa FKBP) (FKBP-52) (59 kDa immunophilin) (p59) (FK506-binding protein 4) (FKBP-4) (FKBP59) (HSP-binding immunophilin) (HBI) (Immunophilin FKBP52) (Rotamase) [Cleaved into: Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed] | Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Also acts as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}. |
| Q02952 | AKAP12 | S19 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q02952 | AKAP12 | S732 | ochoa|psp | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q03164 | KMT2A | S142 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q03164 | KMT2A | S1119 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q03169 | TNFAIP2 | S68 | ochoa | Tumor necrosis factor alpha-induced protein 2 (TNF alpha-induced protein 2) (Primary response gene B94 protein) | May play a role as a mediator of inflammation and angiogenesis. |
| Q03188 | CENPC | S600 | ochoa | Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) | Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}. |
| Q04323 | UBXN1 | S75 | ochoa | UBX domain-containing protein 1 (SAPK substrate protein 1) (UBA/UBX 33.3 kDa protein) | Ubiquitin-binding protein that plays a role in the modulation of innate immune response. Blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, UBXN1 is induced and recruited to the RLR component MAVS. In turn, interferes with MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. This function probably serves as a brake to prevent excessive RLR signaling (PubMed:23545497). Interferes with the TNFalpha-triggered NF-kappa-B pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs) and thereby inhibiting their recruitment to TNFR1 (PubMed:25681446). Also prevents the activation of NF-kappa-B by associating with CUL1 and thus inhibiting NF-kappa-B inhibitor alpha/NFKBIA degradation that remains bound to NF-kappa-B (PubMed:28152074). Interacts with the BRCA1-BARD1 heterodimer and regulates its activity. Specifically binds 'Lys-6'-linked polyubiquitin chains. Interaction with autoubiquitinated BRCA1 leads to the inhibition of the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer (PubMed:20351172). Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. {ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:23545497, ECO:0000269|PubMed:25681446, ECO:0000269|PubMed:28152074}. |
| Q04637 | EIF4G1 | S1097 | ochoa | Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}. |
| Q04726 | TLE3 | S217 | ochoa|psp | Transducin-like enhancer protein 3 (Enhancer of split groucho-like protein 3) (ESG3) | Transcriptional corepressor that binds to a number of transcription factors (PubMed:28689657). Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling (PubMed:28689657). The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity). {ECO:0000250|UniProtKB:Q04724, ECO:0000269|PubMed:28689657}. |
| Q05D32 | CTDSPL2 | S112 | ochoa | CTD small phosphatase-like protein 2 (CTDSP-like 2) (EC 3.1.3.-) | Probable phosphatase. {ECO:0000250}. |
| Q07065 | CKAP4 | S460 | ochoa | Cytoskeleton-associated protein 4 (63-kDa cytoskeleton-linking membrane protein) (Climp-63) (p63) | Mediates the anchoring of the endoplasmic reticulum to microtubules. {ECO:0000269|PubMed:15703217}.; FUNCTION: High-affinity epithelial cell surface receptor for the FZD8-related low molecular weight sialoglycopeptide APF/antiproliferative factor. Mediates the APF antiproliferative signaling within cells. {ECO:0000269|PubMed:17030514, ECO:0000269|PubMed:19144824}. |
| Q07864 | POLE | S2022 | ochoa | DNA polymerase epsilon catalytic subunit A (EC 2.7.7.7) (3'-5' exodeoxyribonuclease) (EC 3.1.11.-) (DNA polymerase II subunit A) | Catalytic component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in chromosomal DNA replication (By similarity). Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199). Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374). {ECO:0000250|UniProtKB:P21951, ECO:0000269|PubMed:10801849, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:27573199}. |
| Q08170 | SRSF4 | S78 | ochoa | Serine/arginine-rich splicing factor 4 (Pre-mRNA-splicing factor SRP75) (SRP001LB) (Splicing factor, arginine/serine-rich 4) | Plays a role in alternative splice site selection during pre-mRNA splicing. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:15009664}. |
| Q08752 | PPID | S198 | ochoa | Peptidyl-prolyl cis-trans isomerase D (PPIase D) (EC 5.2.1.8) (40 kDa peptidyl-prolyl cis-trans isomerase) (Cyclophilin-40) (CYP-40) (Cyclophilin-related protein) (Rotamase D) | PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:11350175, PubMed:20676357). Proposed to act as a co-chaperone in HSP90 complexes such as in unligated steroid receptors heterocomplexes. Different co-chaperones seem to compete for association with HSP90 thus establishing distinct HSP90-co-chaperone-receptor complexes with the potential to exert tissue-specific receptor activity control. May have a preference for estrogen receptor complexes and is not found in glucocorticoid receptor complexes. May be involved in cytoplasmic dynein-dependent movement of the receptor from the cytoplasm to the nucleus. May regulate MYB by inhibiting its DNA-binding activity. Involved in regulation of AHR signaling by promoting the formation of the AHR:ARNT dimer; the function is independent of HSP90 but requires the chaperone activity. Involved in regulation of UV radiation-induced apoptosis. Promotes cell viability in anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALK+ ALCL) cell lines. {ECO:0000269|PubMed:11350175, ECO:0000269|PubMed:18708059, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22681779, ECO:0000269|PubMed:23220213, ECO:0000269|PubMed:9659917}.; FUNCTION: (Microbial infection) May be involved in hepatitis C virus (HCV) replication and release. {ECO:0000269|PubMed:19932913, ECO:0000269|PubMed:21711559}. |
| Q08945 | SSRP1 | S647 | ochoa | FACT complex subunit SSRP1 (Chromatin-specific transcription elongation factor 80 kDa subunit) (Facilitates chromatin transcription complex 80 kDa subunit) (FACT 80 kDa subunit) (FACTp80) (Facilitates chromatin transcription complex subunit SSRP1) (Recombination signal sequence recognition protein 1) (Structure-specific recognition protein 1) (hSSRP1) (T160) | Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63. {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9566881, ECO:0000269|PubMed:9836642}. |
| Q08999 | RBL2 | S373 | ochoa|psp | Retinoblastoma-like protein 2 (130 kDa retinoblastoma-associated protein) (p130) (Retinoblastoma-related protein 2) (RBR-2) (pRb2) | Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor. |
| Q08AD1 | CAMSAP2 | S1325 | ochoa | Calmodulin-regulated spectrin-associated protein 2 (Calmodulin-regulated spectrin-associated protein 1-like protein 1) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153, PubMed:24706919). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:27666745). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (PubMed:24908486). Through the microtubule cytoskeleton, regulates the autophagosome transport (PubMed:28726242). {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:24908486, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28726242}. |
| Q09666 | AHNAK | S18 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S20 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S220 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S256 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S3362 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5464 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5653 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q0VF96 | CGNL1 | S476 | ochoa | Cingulin-like protein 1 (Junction-associated coiled-coil protein) (Paracingulin) | May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons. {ECO:0000269|PubMed:22891260}. |
| Q0VG06 | FAAP100 | S688 | ochoa | Fanconi anemia core complex-associated protein 100 (Fanconi anemia-associated protein of 100 kDa) | Plays a role in Fanconi anemia-associated DNA damage response network. Regulates FANCD2 monoubiquitination and the stability of the FA core complex. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. {ECO:0000269|PubMed:17396147}. |
| Q12770 | SCAP | S826 | ochoa | Sterol regulatory element-binding protein cleavage-activating protein (SCAP) (SREBP cleavage-activating protein) | Escort protein required for cholesterol as well as lipid homeostasis (By similarity). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:26311497). At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (By similarity). Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (PubMed:26311497). Binds cholesterol via its SSD domain (By similarity). {ECO:0000250|UniProtKB:P97260, ECO:0000269|PubMed:26311497}. |
| Q12873 | CHD3 | S597 | ochoa | Chromodomain-helicase-DNA-binding protein 3 (CHD-3) (EC 3.6.4.-) (ATP-dependent helicase CHD3) (Mi-2 autoantigen 240 kDa protein) (Mi2-alpha) (Zinc finger helicase) (hZFH) | ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA (PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666, PubMed:30397230, PubMed:9804427). Involved in transcriptional repression as part of the NuRD complex (PubMed:27068747). Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity (PubMed:17626165). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:27068747, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:30397230, ECO:0000269|PubMed:9804427}. |
| Q12888 | TP53BP1 | S103 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | S625 | psp | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | S1019 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | S1202 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | S1329 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12923 | PTPN13 | S911 | ochoa | Tyrosine-protein phosphatase non-receptor type 13 (EC 3.1.3.48) (Fas-associated protein-tyrosine phosphatase 1) (FAP-1) (PTP-BAS) (Protein-tyrosine phosphatase 1E) (PTP-E1) (hPTPE1) (Protein-tyrosine phosphatase PTPL1) | Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}. |
| Q12929 | EPS8 | S502 | psp | Epidermal growth factor receptor kinase substrate 8 | Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes. {ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031}. |
| Q12955 | ANK3 | S4349 | ochoa | Ankyrin-3 (ANK-3) (Ankyrin-G) | Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}. |
| Q13009 | TIAM1 | S368 | ochoa | Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) | Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}. |
| Q13011 | ECH1 | S36 | ochoa | Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (EC 5.3.3.-) | Isomerization of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA. {ECO:0000250|UniProtKB:Q62651}. |
| Q13123 | IK | S417 | ochoa | Protein Red (Cytokine IK) (IK factor) (Protein RER) | Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:28781166). Auxiliary spliceosomal protein that regulates selection of alternative splice sites in a small set of target pre-mRNA species (Probable). Required for normal mitotic cell cycle progression (PubMed:22351768, PubMed:24252166). Recruits MAD1L1 and MAD2L1 to kinetochores, and is required to trigger the spindle assembly checkpoint (PubMed:22351768). Required for normal accumulation of SMU1 (PubMed:24945353). {ECO:0000269|PubMed:22351768, ECO:0000269|PubMed:24252166, ECO:0000269|PubMed:24945353, ECO:0000269|PubMed:28781166, ECO:0000305}.; FUNCTION: (Microbial infection) Required, together with SMU1, for normal splicing of influenza A virus NS1 pre-mRNA, which is required for the production of the exportin NS2 and for the production of influenza A virus particles. Not required for the production of VSV virus particles. {ECO:0000269|PubMed:24945353}. |
| Q13131 | PRKAA1 | S496 | ochoa|psp | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| Q13136 | PPFIA1 | S666 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13136 | PPFIA1 | S1156 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13148 | TARDBP | S377 | psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q13200 | PSMD2 | S361 | ochoa|psp | 26S proteasome non-ATPase regulatory subunit 2 (26S proteasome regulatory subunit RPN1) (26S proteasome regulatory subunit S2) (26S proteasome subunit p97) (Protein 55.11) (Tumor necrosis factor type 1 receptor-associated protein 2) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}.; FUNCTION: Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1. |
| Q13263 | TRIM28 | S453 | ochoa | Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) | Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}. |
| Q13308 | PTK7 | S337 | ochoa | Inactive tyrosine-protein kinase 7 (Colon carcinoma kinase 4) (CCK-4) (Protein-tyrosine kinase 7) (Pseudo tyrosine kinase receptor 7) (Tyrosine-protein kinase-like 7) | Inactive tyrosine kinase involved in Wnt signaling pathway. Component of both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathway. Functions in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization and apoptosis. Has a role in embryogenesis, epithelial tissue organization and angiogenesis. {ECO:0000269|PubMed:18471990, ECO:0000269|PubMed:20558616, ECO:0000269|PubMed:20837484, ECO:0000269|PubMed:21103379, ECO:0000269|PubMed:21132015}. |
| Q13309 | SKP2 | S75 | ochoa|psp | S-phase kinase-associated protein 2 (Cyclin-A/CDK2-associated protein p45) (F-box protein Skp2) (F-box/LRR-repeat protein 1) (p45skp2) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (PubMed:9736735, PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16262255, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:22770219, PubMed:32267835). Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity). Degradation of CDKN1B/p27kip also requires CKS1 (By similarity). Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, NBN, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:32267835). Degradation of TAL1 also requires STUB1 (PubMed:17962192). Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:9736735, PubMed:16262255). Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219). Following phosphorylation in response to DNA damage, mediates 'Lys-63'-linked ubiquitination of NBN, promoting ATM recruitment to DNA damage sites and DNA repair via homologous recombination (PubMed:22464731). {ECO:0000250|UniProtKB:Q9Z0Z3, ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16103164, ECO:0000269|PubMed:16262255, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:22464731, ECO:0000269|PubMed:22770219, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:9736735}.; FUNCTION: Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. {ECO:0000269|PubMed:27194766}. |
| Q13310 | PABPC4 | S319 | ochoa | Polyadenylate-binding protein 4 (PABP-4) (Poly(A)-binding protein 4) (Activated-platelet protein 1) (APP-1) (Inducible poly(A)-binding protein) (iPABP) | Binds the poly(A) tail of mRNA (PubMed:8524242). Binds to SMIM26 mRNA and plays a role in its post-transcriptional regulation (PubMed:37009826). May be involved in cytoplasmic regulatory processes of mRNA metabolism. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo (By similarity). {ECO:0000250|UniProtKB:P11940, ECO:0000269|PubMed:37009826, ECO:0000269|PubMed:8524242}. |
| Q13310 | PABPC4 | S360 | ochoa | Polyadenylate-binding protein 4 (PABP-4) (Poly(A)-binding protein 4) (Activated-platelet protein 1) (APP-1) (Inducible poly(A)-binding protein) (iPABP) | Binds the poly(A) tail of mRNA (PubMed:8524242). Binds to SMIM26 mRNA and plays a role in its post-transcriptional regulation (PubMed:37009826). May be involved in cytoplasmic regulatory processes of mRNA metabolism. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo (By similarity). {ECO:0000250|UniProtKB:P11940, ECO:0000269|PubMed:37009826, ECO:0000269|PubMed:8524242}. |
| Q13387 | MAPK8IP2 | S254 | ochoa | C-Jun-amino-terminal kinase-interacting protein 2 (JIP-2) (JNK-interacting protein 2) (Islet-brain-2) (IB-2) (JNK MAP kinase scaffold protein 2) (Mitogen-activated protein kinase 8-interacting protein 2) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. JIP2 inhibits IL1 beta-induced apoptosis in insulin-secreting cells. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). {ECO:0000250}. |
| Q13428 | TCOF1 | S178 | ochoa | Treacle protein (Treacher Collins syndrome protein) | Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}. |
| Q13428 | TCOF1 | S1407 | ochoa | Treacle protein (Treacher Collins syndrome protein) | Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}. |
| Q13435 | SF3B2 | S778 | ochoa | Splicing factor 3B subunit 2 (Pre-mRNA-splicing factor SF3b 145 kDa subunit) (SF3b145) (Spliceosome-associated protein 145) (SAP 145) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:12234937, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B2 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937, PubMed:27720643). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| Q13443 | ADAM9 | S752 | ochoa | Disintegrin and metalloproteinase domain-containing protein 9 (ADAM 9) (EC 3.4.24.-) (Cellular disintegrin-related protein) (Meltrin-gamma) (Metalloprotease/disintegrin/cysteine-rich protein 9) (Myeloma cell metalloproteinase) | Metalloprotease that cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins. {ECO:0000250|UniProtKB:Q61072}.; FUNCTION: [Isoform 2]: May act as alpha-secretase for amyloid precursor protein (APP). {ECO:0000269|PubMed:12054541}. |
| Q13459 | MYO9B | S1267 | ochoa | Unconventional myosin-IXb (Unconventional myosin-9b) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}. |
| Q13459 | MYO9B | S1294 | ochoa | Unconventional myosin-IXb (Unconventional myosin-9b) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}. |
| Q13459 | MYO9B | S1408 | ochoa | Unconventional myosin-IXb (Unconventional myosin-9b) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}. |
| Q13555 | CAMK2G | S381 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit gamma (CaM kinase II subunit gamma) (CaMK-II subunit gamma) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q923T9, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:30184290}. |
| Q13573 | SNW1 | S481 | ochoa | SNW domain-containing protein 1 (Nuclear protein SkiP) (Nuclear receptor coactivator NCoA-62) (Ski-interacting protein) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. {ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:11514567, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12840015, ECO:0000269|PubMed:14985122, ECO:0000269|PubMed:15194481, ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:19818711, ECO:0000269|PubMed:21245387, ECO:0000269|PubMed:21460037, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:9632709, ECO:0000305|PubMed:33509932}.; FUNCTION: (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. {ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:19818711}.; FUNCTION: (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. {ECO:0000269|PubMed:10644367}. |
| Q13613 | MTMR1 | S39 | ochoa | Phosphatidylinositol-3-phosphate phosphatase MTMR1 (EC 3.1.3.-) (Myotubularin-related protein 1) (Phosphatidylinositol-3,5-bisphosphate 3-phosphatase) (EC 3.1.3.95) | Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate, generating phosphatidylinositol (PubMed:11733541, PubMed:27018598). Could also dephosphorylate phosphatidylinositol 3,5-bisphosphate to produce phosphatidylinositol 5-phosphate (PubMed:27018598). {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:27018598}. |
| Q13671 | RIN1 | S719 | ochoa | Ras and Rab interactor 1 (Ras inhibitor JC99) (Ras interaction/interference protein 1) | Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. Can affect Ras signaling at different levels. First, by competing with RAF1 protein for binding to activated Ras. Second, by enhancing signaling from ABL1 and ABL2, which regulate cytoskeletal remodeling. Third, by activating RAB5A, possibly by functioning as a guanine nucleotide exchange factor (GEF) for RAB5A, by exchanging bound GDP for free GTP, and facilitating Ras-activated receptor endocytosis. {ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9208849}. |
| Q13796 | SHROOM2 | S1427 | ochoa | Protein Shroom2 (Apical-like protein) (Protein APXL) | May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution (By similarity). {ECO:0000250}. |
| Q13835 | PKP1 | S69 | psp | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q13835 | PKP1 | S134 | ochoa | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q13905 | RAPGEF1 | S338 | ochoa | Rap guanine nucleotide exchange factor 1 (CRK SH3-binding GNRP) (Guanine nucleotide-releasing factor 2) (Protein C3G) | Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}. |
| Q14005 | IL16 | S1037 | ochoa | Pro-interleukin-16 [Cleaved into: Interleukin-16 (IL-16) (Lymphocyte chemoattractant factor) (LCF)] | Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4.; FUNCTION: [Isoform 1]: May act as a scaffolding protein that anchors ion channels in the membrane.; FUNCTION: Isoform 3 is involved in cell cycle progression in T-cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells. |
| Q14123 | PDE1C | S488 | ochoa | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (Cam-PDE 1C) (EC 3.1.4.17) (Hcam3) | Calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:29860631, PubMed:8557689). Has a high affinity for both cAMP and cGMP (PubMed:8557689). Modulates the amplitude and duration of the cAMP signal in sensory cilia in response to odorant stimulation, hence contributing to the generation of action potentials. Regulates smooth muscle cell proliferation. Regulates the stability of growth factor receptors, including PDGFRB (Probable). {ECO:0000269|PubMed:29860631, ECO:0000269|PubMed:8557689, ECO:0000305|PubMed:29860631}. |
| Q14141 | SEPTIN6 | S411 | ochoa | Septin-6 | Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Involved in cytokinesis. May play a role in HCV RNA replication. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). {ECO:0000269|PubMed:17229681, ECO:0000269|PubMed:17803907, ECO:0000305|PubMed:25588830}. |
| Q14147 | DHX34 | S749 | ochoa | Probable ATP-dependent RNA helicase DHX34 (EC 3.6.4.13) (DEAH box protein 34) (DExH-box helicase 34) | Probable ATP-binding RNA helicase required for nonsense-mediated decay (NMD) degradation of mRNA transcripts containing premature stop codons (PubMed:25220460, PubMed:33205750). Promotes the phosphorylation of UPF1 along with its interaction with key NMD pathway proteins UPF2 and EIF4A3 (PubMed:25220460). Interaction with the RUVBL1-RUVBL2 complex results in loss of nucleotide binding ability and ATP hydrolysis of the complex (PubMed:33205750). Negatively regulates the nucleotide binding ability and ATP hydrolysis of the RUVBL1-RUVBL2 complex via induction of N-terminus conformation changes of the RUVBL2 subunits (PubMed:33205750). {ECO:0000269|PubMed:25220460, ECO:0000269|PubMed:33205750}. |
| Q14152 | EIF3A | S495 | ochoa | Eukaryotic translation initiation factor 3 subunit A (eIF3a) (Eukaryotic translation initiation factor 3 subunit 10) (eIF-3-theta) (eIF3 p167) (eIF3 p180) (eIF3 p185) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:11169732, PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815). {ECO:0000255|HAMAP-Rule:MF_03000, ECO:0000269|PubMed:11169732, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634). {ECO:0000269|PubMed:23766293, ECO:0000269|PubMed:24357634}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| Q14152 | EIF3A | S1028 | ochoa | Eukaryotic translation initiation factor 3 subunit A (eIF3a) (Eukaryotic translation initiation factor 3 subunit 10) (eIF-3-theta) (eIF3 p167) (eIF3 p180) (eIF3 p185) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:11169732, PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815). {ECO:0000255|HAMAP-Rule:MF_03000, ECO:0000269|PubMed:11169732, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634). {ECO:0000269|PubMed:23766293, ECO:0000269|PubMed:24357634}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| Q14153 | FAM53B | S151 | ochoa | Protein FAM53B (Protein simplet) | Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization. {ECO:0000269|PubMed:25183871}. |
| Q14153 | FAM53B | S201 | ochoa | Protein FAM53B (Protein simplet) | Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization. {ECO:0000269|PubMed:25183871}. |
| Q14160 | SCRIB | S748 | ochoa | Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) | Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750, ECO:0000269|PubMed:27380321}. |
| Q14203 | DCTN1 | S351 | ochoa | Dynactin subunit 1 (150 kDa dynein-associated polypeptide) (DAP-150) (DP-150) (p135) (p150-glued) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule (PubMed:25185702). Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon (PubMed:23874158). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole (PubMed:23386061). Plays a role in primary cilia formation (PubMed:25774020). {ECO:0000250|UniProtKB:A0A287B8J2, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23386061, ECO:0000269|PubMed:23874158, ECO:0000269|PubMed:25185702, ECO:0000269|PubMed:25774020}. |
| Q14207 | NPAT | S1273 | ochoa | Protein NPAT (Nuclear protein of the ataxia telangiectasia mutated locus) (Nuclear protein of the ATM locus) (p220) | Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters. {ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:12665581, ECO:0000269|PubMed:12724424, ECO:0000269|PubMed:14585971, ECO:0000269|PubMed:14612403, ECO:0000269|PubMed:15555599, ECO:0000269|PubMed:15988025, ECO:0000269|PubMed:16131487, ECO:0000269|PubMed:17163457, ECO:0000269|PubMed:17826007, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:17974976, ECO:0000269|PubMed:9472014}. |
| Q14247 | CTTN | S47 | ochoa | Src substrate cortactin (Amplaxin) (Oncogene EMS1) | Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}. |
| Q14315 | FLNC | S2233 | ochoa|psp | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14315 | FLNC | S2236 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14376 | GALE | S44 | ochoa | UDP-glucose 4-epimerase (EC 5.1.3.2) (Galactowaldenase) (UDP-N-acetylgalactosamine 4-epimerase) (UDP-GalNAc 4-epimerase) (UDP-N-acetylglucosamine 4-epimerase) (UDP-GlcNAc 4-epimerase) (EC 5.1.3.7) (UDP-galactose 4-epimerase) | Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids. {ECO:0000269|PubMed:22654673, ECO:0000303|PubMed:23732289}. |
| Q14451 | GRB7 | S361 | ochoa|psp | Growth factor receptor-bound protein 7 (B47) (Epidermal growth factor receptor GRB-7) (GRB7 adapter protein) | Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. Promotes activation of down-stream protein kinases, including STAT3, AKT1, MAPK1 and/or MAPK3. Promotes activation of HRAS. Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration. Plays a role in the assembly and stability of RNA stress granules. Binds to the 5'UTR of target mRNA molecules and represses translation of target mRNA species, when not phosphorylated. Phosphorylation impairs RNA binding and promotes stress granule disassembly during recovery after cellular stress (By similarity). {ECO:0000250, ECO:0000269|PubMed:10893408, ECO:0000269|PubMed:12021278, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:20622016}. |
| Q14457 | BECN1 | S409 | ochoa|psp | Beclin-1 (Coiled-coil myosin-like BCL2-interacting protein) (Protein GT197) [Cleaved into: Beclin-1-C 35 kDa; Beclin-1-C 37 kDa] | Plays a central role in autophagy (PubMed:18570871, PubMed:21358617, PubMed:23184933, PubMed:23974797, PubMed:25484083, PubMed:28445460, PubMed:37776275). Acts as a core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abscission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530, PubMed:20643123, PubMed:23974797, PubMed:26783301). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521). May play a role in antiviral host defense. {ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:21358617, ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23974797, ECO:0000269|PubMed:25275521, ECO:0000269|PubMed:25484083, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:37776275, ECO:0000269|PubMed:9765397}.; FUNCTION: Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors. {ECO:0000269|PubMed:21364619, ECO:0000269|PubMed:26263979}.; FUNCTION: (Microbial infection) Protects against infection by a neurovirulent strain of Sindbis virus. {ECO:0000269|PubMed:9765397}. |
| Q14494 | NFE2L1 | S599 | psp | Endoplasmic reticulum membrane sensor NFE2L1 (Locus control region-factor 1) (LCR-F1) (Nuclear factor erythroid 2-related factor 1) (NF-E2-related factor 1) (NFE2-related factor 1) (Nuclear factor, erythroid derived 2, like 1) (Protein NRF1, p120 form) (Transcription factor 11) (TCF-11) [Cleaved into: Transcription factor NRF1 (Protein NRF1, p110 form)] | [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20932482). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 (By similarity). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36 (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (PubMed:20932482). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}.; FUNCTION: [Transcription factor NRF1]: CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses (PubMed:8932385, PubMed:9421508). Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response (PubMed:8932385, PubMed:9421508). Activates or represses expression of target genes, depending on the context (PubMed:8932385, PubMed:9421508). Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess, such as CD36 (By similarity). In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (By similarity). Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1 and MT2 (By similarity). Plays an essential role during fetal liver hematopoiesis: probably has a protective function against oxidative stress and is involved in lipid homeostasis in the liver (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits (PubMed:20932482). Also involved in regulating glucose flux (By similarity). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (PubMed:15308669). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts. {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:8932385, ECO:0000269|PubMed:9421508}. |
| Q14511 | NEDD9 | S312 | ochoa | Enhancer of filamentation 1 (hEF1) (CRK-associated substrate-related protein) (CAS-L) (CasL) (Cas scaffolding protein family member 2) (CASS2) (Neural precursor cell expressed developmentally down-regulated protein 9) (NEDD-9) (Renal carcinoma antigen NY-REN-12) (p105) [Cleaved into: Enhancer of filamentation 1 p55] | Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion (PubMed:24574519). As a focal adhesion protein, plays a role in embryonic fibroblast migration (By similarity). May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKL and SHPTP2 to the tyrosine phosphorylated form (PubMed:9020138). Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs (PubMed:17174122). Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse (By similarity). Negatively regulates cilia outgrowth in polarized cysts (By similarity). Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723). Positively regulates RANKL-induced osteoclastogenesis (By similarity). Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory (By similarity). {ECO:0000250|UniProtKB:A0A8I3PDQ1, ECO:0000250|UniProtKB:O35177, ECO:0000269|PubMed:17174122, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:24574519, ECO:0000269|PubMed:9020138}. |
| Q14517 | FAT1 | S4476 | ochoa | Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form] | [Protocadherin Fat 1]: Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. {ECO:0000250}. |
| Q14524 | SCN5A | S1503 | psp | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q14527 | HLTF | S188 | ochoa | Helicase-like transcription factor (EC 2.3.2.27) (EC 3.6.4.-) (DNA-binding protein/plasminogen activator inhibitor 1 regulator) (HIP116) (RING finger protein 80) (RING-type E3 ubiquitin transferase HLTF) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3) (Sucrose nonfermenting protein 2-like 3) | Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA. {ECO:0000250, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:7876228, ECO:0000269|PubMed:8672239, ECO:0000269|PubMed:9126292}. |
| Q14669 | TRIP12 | S161 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14671 | PUM1 | S98 | ochoa | Pumilio homolog 1 (HsPUM) (Pumilio-1) | Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:18328718, PubMed:21397187, PubMed:21572425, PubMed:21653694). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000250|UniProtKB:Q80U78, ECO:0000269|PubMed:18328718, ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:20818387, ECO:0000269|PubMed:20860814, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:21572425, ECO:0000269|PubMed:21653694, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25768905, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:29474920}. |
| Q14674 | ESPL1 | S1508 | ochoa|psp | Separin (EC 3.4.22.49) (Caspase-like protein ESPL1) (Extra spindle poles-like 1 protein) (Separase) | Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}. |
| Q14676 | MDC1 | S376 | ochoa|psp | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14676 | MDC1 | S955 | ochoa | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14684 | RRP1B | S505 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14761 | PTPRCAP | S163 | ochoa|psp | Protein tyrosine phosphatase receptor type C-associated protein (PTPRC-associated protein) (CD45-associated protein) (CD45-AP) (Lymphocyte phosphatase-associated phosphoprotein) | None |
| Q14814 | MEF2D | S477 | ochoa | Myocyte-specific enhancer factor 2D | Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity). {ECO:0000250, ECO:0000269|PubMed:10849446, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15743823, ECO:0000269|PubMed:15834131}. |
| Q14839 | CHD4 | S221 | ochoa | Chromodomain-helicase-DNA-binding protein 4 (CHD-4) (EC 3.6.4.-) (ATP-dependent helicase CHD4) (Mi-2 autoantigen 218 kDa protein) (Mi2-beta) | ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA (PubMed:28977666, PubMed:32543371). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:17626165, PubMed:28977666, PubMed:9804427). Localizes to acetylated damaged chromatin in a ZMYND8-dependent manner, to promote transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309). Involved in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q6PDQ2, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:32543371, ECO:0000269|PubMed:9804427}. |
| Q14847 | LASP1 | S150 | ochoa | LIM and SH3 domain protein 1 (LASP-1) (Metastatic lymph node gene 50 protein) (MLN 50) | Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types (By similarity). {ECO:0000250}. |
| Q14978 | NOLC1 | S681 | ochoa | Nucleolar and coiled-body phosphoprotein 1 (140 kDa nucleolar phosphoprotein) (Nopp140) (Hepatitis C virus NS5A-transactivated protein 13) (HCV NS5A-transactivated protein 13) (Nucleolar 130 kDa protein) (Nucleolar phosphoprotein p130) | Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:10567578, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with TCOF1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in nucleologenesis, possibly by playing a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus (PubMed:9016786). It has intrinsic GTPase and ATPase activities (PubMed:9016786). {ECO:0000269|PubMed:10567578, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:9016786}. |
| Q14993 | COL19A1 | S81 | ochoa | Collagen alpha-1(XIX) chain (Collagen alpha-1(Y) chain) | May act as a cross-bridge between fibrils and other extracellular matrix molecules. Involved in skeletal myogenesis in the developing esophagus. May play a role in organization of the pericellular matrix or the sphinteric smooth muscle. {ECO:0000269|PubMed:12788917}. |
| Q14997 | PSME4 | S1746 | ochoa | Proteasome activator complex subunit 4 (Proteasome activator PA200) (Protein BLM10 homolog) (Blm10) (hBlm10) | Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks. {ECO:0000269|PubMed:12093752, ECO:0000269|PubMed:18845680, ECO:0000269|PubMed:22550082, ECO:0000269|PubMed:23706739}. |
| Q14CW9 | ATXN7L3 | S326 | ochoa | Ataxin-7-like protein 3 (SAGA-associated factor 11 homolog) | Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B (PubMed:18206972, PubMed:21746879). The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. Within the complex, it is required to recruit USP22 and ENY2 into the SAGA complex (PubMed:18206972). Regulates H2B monoubiquitination (H2Bub1) levels. Affects subcellular distribution of ENY2, USP22 and ATXN7L3B (PubMed:27601583). {ECO:0000255|HAMAP-Rule:MF_03047, ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:21746879, ECO:0000269|PubMed:27601583}. |
| Q14D04 | VEPH1 | S420 | ochoa | Ventricular zone-expressed PH domain-containing protein homolog 1 (Protein melted) | Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}. |
| Q15007 | WTAP | S281 | ochoa | Pre-mRNA-splicing regulator WTAP (Female-lethal(2)D homolog) (hFL(2)D) (WT1-associated protein) (Wilms tumor 1-associating protein) | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Required for accumulation of METTL3 and METTL14 to nuclear speckle (PubMed:24316715, PubMed:24407421, PubMed:24981863). Acts as a mRNA splicing regulator (PubMed:12444081). Regulates G2/M cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances its stability (PubMed:17088532). Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes (PubMed:17095724). {ECO:0000269|PubMed:12444081, ECO:0000269|PubMed:17088532, ECO:0000269|PubMed:17095724, ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:24981863, ECO:0000269|PubMed:29507755}. |
| Q15014 | MORF4L2 | S90 | ochoa | Mortality factor 4-like protein 2 (MORF-related gene X protein) (Protein MSL3-2) (Transcription factor-like protein MRGX) | Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also a component of the MSIN3A complex which acts to repress transcription by deacetylation of nucleosomal histones. |
| Q15018 | ABRAXAS2 | S339 | ochoa | BRISC complex subunit Abraxas 2 (Abraxas brother protein 1) (Protein FAM175B) | Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148). {ECO:0000250|UniProtKB:Q3TCJ1, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20032457, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25283148}. |
| Q15056 | EIF4H | S21 | ochoa | Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) | Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}. |
| Q15056 | EIF4H | S24 | ochoa | Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) | Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}. |
| Q15056 | EIF4H | S193 | ochoa | Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) | Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}. |
| Q15075 | EEA1 | S18 | ochoa | Early endosome antigen 1 (Endosome-associated protein p162) (Zinc finger FYVE domain-containing protein 2) | Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking. |
| Q15084 | PDIA6 | S394 | ochoa | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| Q15139 | PRKD1 | S345 | ochoa | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q15149 | PLEC | S4642 | ochoa|psp | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15172 | PPP2R5A | S49 | ochoa | Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform (PP2A B subunit isoform B'-alpha) (PP2A B subunit isoform B56-alpha) (PP2A B subunit isoform PR61-alpha) (PR61alpha) (PP2A B subunit isoform R5-alpha) | The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment. |
| Q15233 | NONO | S262 | ochoa | Non-POU domain-containing octamer-binding protein (NonO protein) (54 kDa nuclear RNA- and DNA-binding protein) (p54(nrb)) (p54nrb) (55 kDa nuclear protein) (NMT55) (DNA-binding p52/p100 complex, 52 kDa subunit) | DNA- and RNA binding protein, involved in several nuclear processes (PubMed:11525732, PubMed:12403470, PubMed:26571461). Binds the conventional octamer sequence in double-stranded DNA (PubMed:11525732, PubMed:12403470, PubMed:26571461). Also binds single-stranded DNA and RNA at a site independent of the duplex site (PubMed:11525732, PubMed:12403470, PubMed:26571461). Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ (PubMed:11525732, PubMed:12403470, PubMed:26571461). Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b (PubMed:12403470). Together with PSPC1, required for the formation of nuclear paraspeckles (PubMed:22416126). The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs (PubMed:11525732). The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1 (PubMed:10858305). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends (PubMed:15590677). In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex (PubMed:15590677). NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (PubMed:11897684). NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (By similarity). Important for the functional organization of GABAergic synapses (By similarity). Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript (By similarity). Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728, PubMed:30270045). Promotes activation of the cGAS-STING pathway in response to HIV-2 infection: acts by interacting with HIV-2 Capsid protein p24, thereby promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation (PubMed:30270045). In contrast, the weak interaction with HIV-1 Capsid protein p24 does not allow activation of the cGAS-STING pathway (PubMed:30270045). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:12403470, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:30270045}. |
| Q15303 | ERBB4 | S726 | ochoa | Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)] | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}. |
| Q15424 | SAFB | S803 | ochoa | Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) | Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}. |
| Q15459 | SF3A1 | S508 | ochoa | Splicing factor 3A subunit 1 (SF3a120) (Spliceosome-associated protein 114) (SAP 114) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10882114, PubMed:11533230, PubMed:32494006). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:10882114, PubMed:11533230, PubMed:32494006). Within the 17S U2 SnRNP complex, SF3A1 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes (PubMed:29360106, PubMed:30315277). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:11533230, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:32494006}. |
| Q15596 | NCOA2 | S675 | ochoa | Nuclear receptor coactivator 2 (NCoA-2) (Class E basic helix-loop-helix protein 75) (bHLHe75) (Transcriptional intermediary factor 2) (hTIF2) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:22504882, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:26553876, ECO:0000269|PubMed:8670870, ECO:0000269|PubMed:9430642}. |
| Q15599 | NHERF2 | S280 | ochoa | Na(+)/H(+) exchange regulatory cofactor NHE-RF2 (NHERF-2) (NHE3 kinase A regulatory protein E3KARP) (SRY-interacting protein 1) (SIP-1) (Sodium-hydrogen exchanger regulatory factor 2) (Solute carrier family 9 isoform A3 regulatory factor 2) (Tyrosine kinase activator protein 1) (TKA-1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus. {ECO:0000269|PubMed:10455146, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:9096337}. |
| Q15722 | LTB4R | S310 | ochoa|psp | Leukotriene B4 receptor 1 (LTB4-R 1) (LTB4-R1) (Chemoattractant receptor-like 1) (G-protein coupled receptor 16) (P2Y purinoceptor 7) (P2Y7) | Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y receptor involved in the regulation of cardiac muscle contraction through modulation of L-type calcium currents. Is a receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response. |
| Q15772 | SPEG | S2014 | ochoa | Striated muscle preferentially expressed protein kinase (EC 2.7.11.1) (Aortic preferentially expressed protein 1) (APEG-1) | Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells. |
| Q15772 | SPEG | S2443 | ochoa | Striated muscle preferentially expressed protein kinase (EC 2.7.11.1) (Aortic preferentially expressed protein 1) (APEG-1) | Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells. |
| Q15772 | SPEG | S2448 | ochoa | Striated muscle preferentially expressed protein kinase (EC 2.7.11.1) (Aortic preferentially expressed protein 1) (APEG-1) | Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells. |
| Q15776 | ZKSCAN8 | S201 | ochoa | Zinc finger protein with KRAB and SCAN domains 8 (LD5-1) (Zinc finger protein 192) | May be involved in transcriptional regulation. |
| Q15942 | ZYX | S288 | ochoa | Zyxin (Zyxin-2) | Adhesion plaque protein. Binds alpha-actinin and the CRP protein. Important for targeting TES and ENA/VASP family members to focal adhesions and for the formation of actin-rich structures. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression (By similarity). {ECO:0000250}. |
| Q15942 | ZYX | S290 | ochoa | Zyxin (Zyxin-2) | Adhesion plaque protein. Binds alpha-actinin and the CRP protein. Important for targeting TES and ENA/VASP family members to focal adhesions and for the formation of actin-rich structures. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression (By similarity). {ECO:0000250}. |
| Q16625 | OCLN | S490 | psp | Occludin | May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions. {ECO:0000269|PubMed:19114660}.; FUNCTION: (Microbial infection) Acts as a coreceptor for hepatitis C virus (HCV) in hepatocytes. {ECO:0000269|PubMed:19182773, ECO:0000269|PubMed:20375010}. |
| Q16643 | DBN1 | S307 | ochoa | Drebrin (Developmentally-regulated brain protein) | Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (PubMed:20215400). Required for actin polymerization at immunological synapses (IS) and for the recruitment of the chemokine receptor CXCR4 to IS (PubMed:20215400). Plays a role in dendritic spine morphogenesis and organization, including the localization of the dopamine receptor DRD1 to the dendritic spines (By similarity). Involved in memory-related synaptic plasticity in the hippocampus (By similarity). {ECO:0000250|UniProtKB:Q9QXS6, ECO:0000269|PubMed:20215400}. |
| Q16825 | PTPN21 | S673 | ochoa | Tyrosine-protein phosphatase non-receptor type 21 (EC 3.1.3.48) (Protein-tyrosine phosphatase D1) | None |
| Q16832 | DDR2 | S467 | ochoa | Discoidin domain-containing receptor 2 (Discoidin domain receptor 2) (EC 2.7.10.1) (CD167 antigen-like family member B) (Discoidin domain-containing receptor tyrosine kinase 2) (Neurotrophic tyrosine kinase, receptor-related 3) (Receptor protein-tyrosine kinase TKT) (Tyrosine-protein kinase TYRO10) (CD antigen CD167b) | Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416, ECO:0000269|PubMed:9659899}. |
| Q17R98 | ZNF827 | S152 | ochoa | Zinc finger protein 827 | As part of a ribonucleoprotein complex composed at least of HNRNPK, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). Could also recruit the nucleosome remodeling and histone deacetylase/NuRD complex to telomeric regions of chromosomes to regulate chromatin remodeling as part of telomere maintenance (PubMed:25150861). {ECO:0000269|PubMed:25150861, ECO:0000269|PubMed:33174841}. |
| Q27J81 | INF2 | S1204 | ochoa | Inverted formin-2 (HBEBP2-binding protein C) | Severs actin filaments and accelerates their polymerization and depolymerization. {ECO:0000250}. |
| Q2KJY2 | KIF26B | S984 | ochoa | Kinesin-like protein KIF26B | Essential for embryonic kidney development. Plays an important role in the compact adhesion between mesenchymal cells adjacent to the ureteric buds, possibly by interacting with MYH10. This could lead to the establishment of the basolateral integrity of the mesenchyme and the polarized expression of ITGA8, which maintains the GDNF expression required for further ureteric bud attraction. Although it seems to lack ATPase activity it is constitutively associated with microtubules (By similarity). {ECO:0000250}. |
| Q2LD37 | BLTP1 | S1805 | ochoa | Bridge-like lipid transfer protein family member 1 (Fragile site-associated protein) | Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum (Probable). Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics (PubMed:30906834). Acts as a regulator of phagocytosis (PubMed:31540829). {ECO:0000269|PubMed:30906834, ECO:0000269|PubMed:31540829, ECO:0000305|PubMed:35015055, ECO:0000305|PubMed:35491307}. |
| Q2M2I3 | FAM83E | S386 | ochoa | Protein FAM83E | May play a role in MAPK signaling. {ECO:0000303|PubMed:24736947}. |
| Q2M2I8 | AAK1 | S618 | ochoa | AP2-associated protein kinase 1 (EC 2.7.11.1) (Adaptor-associated kinase 1) | Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:17494869, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124). {ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:11877461, ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:21464124, ECO:0000269|PubMed:25653444}.; FUNCTION: (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue. {ECO:0000269|PubMed:25653444, ECO:0000305|PubMed:31136173}. |
| Q2M389 | WASHC4 | S19 | ochoa | WASH complex subunit 4 (Strumpellin and WASH-interacting protein) (SWIP) (WASH complex subunit SWIP) | Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. {ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:20498093, ECO:0000303|PubMed:21498477}. |
| Q2M3G4 | SHROOM1 | S314 | ochoa | Protein Shroom1 (Apical protein 2) | May be involved in the assembly of microtubule arrays during cell elongation. {ECO:0000250}. |
| Q32MZ4 | LRRFIP1 | S120 | ochoa | Leucine-rich repeat flightless-interacting protein 1 (LRR FLII-interacting protein 1) (GC-binding factor 2) (TAR RNA-interacting protein) | Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:10364563, ECO:0000269|PubMed:14522076, ECO:0000269|PubMed:16199883, ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:9705290}. |
| Q32P44 | EML3 | S204 | ochoa | Echinoderm microtubule-associated protein-like 3 (EMAP-3) | Regulates mitotic spindle assembly, microtubule (MT)-kinetochore attachment and chromosome separation via recruitment of HAUS augmin-like complex and TUBG1 to the existing MTs and promoting MT-based MT nucleation (PubMed:30723163). Required for proper alignnment of chromosomes during metaphase (PubMed:18445686). {ECO:0000269|PubMed:18445686, ECO:0000269|PubMed:30723163}. |
| Q32P51 | HNRNPA1L2 | S142 | ochoa | Heterogeneous nuclear ribonucleoprotein A1-like 2 (hnRNP A1-like 2) (hnRNP core protein A1-like 2) | Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. {ECO:0000250}. |
| Q3MIP1 | ITPRIPL2 | S139 | ochoa | Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 | None |
| Q4VCS5 | AMOT | S319 | ochoa | Angiomotin | Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions. Repressor of YAP1 and WWTR1/TAZ transcription of target genes, potentially via regulation of Hippo signaling-mediated phosphorylation of YAP1 which results in its recruitment to tight junctions (PubMed:21205866). {ECO:0000269|PubMed:11257124, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:21205866}. |
| Q53ET0 | CRTC2 | S613 | ochoa | CREB-regulated transcription coactivator 2 (Transducer of regulated cAMP response element-binding protein 2) (TORC-2) (Transducer of CREB protein 2) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:14536081, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:16809310, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223}. |
| Q53F19 | NCBP3 | S73 | ochoa | Nuclear cap-binding protein subunit 3 (Protein ELG) | Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. NCBP3 serves as adapter protein linking the capped RNAs (m7GpppG-capped RNA) to NCBP1/CBP80. Unlike the conventional CBC with NCBP2 which binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus, the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role in only mRNA export. The alternative CBC is particularly important in cellular stress situations such as virus infections and the NCBP3 activity is critical to inhibit virus growth (PubMed:26382858). {ECO:0000269|PubMed:26382858}. |
| Q53TN4 | CYBRD1 | S248 | ochoa | Plasma membrane ascorbate-dependent reductase CYBRD1 (EC 7.2.1.3) (Cytochrome b reductase 1) (Duodenal cytochrome b) (Ferric-chelate reductase 3) | Plasma membrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) into Fe(2+) (PubMed:30272000). Probably functions in dietary iron absorption at the brush border of duodenal enterocytes by producing Fe(2+), the divalent form of iron that can be transported into enterocytes (PubMed:30272000). It is also able to reduce extracellular monodehydro-L-ascorbate and may be involved in extracellular ascorbate regeneration by erythrocytes in blood (PubMed:17068337). May also act as a ferrireductase in airway epithelial cells (Probable). May also function as a cupric transmembrane reductase (By similarity). {ECO:0000250|UniProtKB:Q925G2, ECO:0000269|PubMed:17068337, ECO:0000269|PubMed:30272000, ECO:0000305|PubMed:16510471}. |
| Q562E7 | WDR81 | S681 | ochoa | WD repeat-containing protein 81 | Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (PubMed:28404643). May also be involved in maintenance of normal mitochondrial structure and organization (By similarity). {ECO:0000250|UniProtKB:Q5ND34, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989, ECO:0000269|PubMed:28404643}. |
| Q5FWE3 | PRRT3 | S774 | ochoa | Proline-rich transmembrane protein 3 | None |
| Q5JRA6 | MIA3 | S1706 | ochoa | Transport and Golgi organization protein 1 homolog (TANGO1) (C219-reactive peptide) (D320) (Melanoma inhibitory activity protein 3) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum (PubMed:19269366, PubMed:27138255). Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES (PubMed:28442536). {ECO:0000269|PubMed:19269366, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:28442536}. |
| Q5JRA6 | MIA3 | S1731 | ochoa | Transport and Golgi organization protein 1 homolog (TANGO1) (C219-reactive peptide) (D320) (Melanoma inhibitory activity protein 3) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum (PubMed:19269366, PubMed:27138255). Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES (PubMed:28442536). {ECO:0000269|PubMed:19269366, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:28442536}. |
| Q5JSL3 | DOCK11 | S1240 | ochoa | Dedicator of cytokinesis protein 11 (Activated Cdc42-associated guanine nucleotide exchange factor) (ACG) (Zizimin-2) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP (PubMed:37342957). Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology (By similarity). Facilitates filopodia formation through the activation of CDC42 (PubMed:37342957). {ECO:0000250|UniProtKB:A2AF47, ECO:0000269|PubMed:37342957}. |
| Q5JSZ5 | PRRC2B | S232 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JSZ5 | PRRC2B | S1801 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JTH9 | RRP12 | S1217 | ochoa | RRP12-like protein | None |
| Q5PRF9 | SAMD4B | S555 | ochoa | Protein Smaug homolog 2 (Smaug 2) (hSmaug2) (Sterile alpha motif domain-containing protein 4B) (SAM domain-containing protein 4B) | Has transcriptional repressor activity. Overexpression inhibits the transcriptional activities of AP-1, p53/TP53 and CDKN1A. {ECO:0000269|PubMed:20510020}. |
| Q5PRF9 | SAMD4B | S626 | ochoa | Protein Smaug homolog 2 (Smaug 2) (hSmaug2) (Sterile alpha motif domain-containing protein 4B) (SAM domain-containing protein 4B) | Has transcriptional repressor activity. Overexpression inhibits the transcriptional activities of AP-1, p53/TP53 and CDKN1A. {ECO:0000269|PubMed:20510020}. |
| Q5QJE6 | DNTTIP2 | S41 | ochoa | Deoxynucleotidyltransferase terminal-interacting protein 2 (Estrogen receptor-binding protein) (LPTS-interacting protein 2) (LPTS-RP2) (Terminal deoxynucleotidyltransferase-interacting factor 2) (TdIF2) (TdT-interacting factor 2) | Regulates the transcriptional activity of DNTT and ESR1. May function as a chromatin remodeling protein (PubMed:12786946, PubMed:15047147). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:12786946, ECO:0000269|PubMed:15047147, ECO:0000269|PubMed:34516797}. |
| Q5SW79 | CEP170 | S1273 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5SYE7 | NHSL1 | S301 | ochoa | NHS-like protein 1 | None |
| Q5T0N5 | FNBP1L | S505 | ochoa | Formin-binding protein 1-like (Transducer of Cdc42-dependent actin assembly protein 1) (Toca-1) | Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. May bind to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promote membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by activating the WASL/N-WASP-WASPIP/WIP complex, the predominant form of WASL/N-WASP in cells. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Essential for autophagy of intracellular bacterial pathogens. {ECO:0000269|PubMed:15260990, ECO:0000269|PubMed:16326391, ECO:0000269|PubMed:19342671}. |
| Q5T1M5 | FKBP15 | S1145 | ochoa | FK506-binding protein 15 (FKBP-15) (133 kDa FK506-binding protein) (133 kDa FKBP) (FKBP-133) (WASP- and FKBP-like protein) (WAFL) | May be involved in the cytoskeletal organization of neuronal growth cones. Seems to be inactive as a PPIase (By similarity). Involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement. {ECO:0000250, ECO:0000269|PubMed:19121306}. |
| Q5T1R4 | HIVEP3 | S1017 | ochoa | Transcription factor HIVEP3 (Human immunodeficiency virus type I enhancer-binding protein 3) (Kappa-B and V(D)J recombination signal sequences-binding protein) (Kappa-binding protein 1) (KBP-1) (Zinc finger protein ZAS3) | Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-alpha-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and pro-inflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation. {ECO:0000269|PubMed:11161801}. |
| Q5T200 | ZC3H13 | S1455 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5T4S7 | UBR4 | S2895 | ochoa | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| Q5T8D3 | ACBD5 | S441 | ochoa | Acyl-CoA-binding domain-containing protein 5 | Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters. {ECO:0000269|PubMed:24535825}. |
| Q5T8P6 | RBM26 | S496 | ochoa | RNA-binding protein 26 (CTCL tumor antigen se70-2) (RNA-binding motif protein 26) | May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}. |
| Q5TC79 | ZBTB37 | S314 | ochoa | Zinc finger and BTB domain-containing protein 37 | May be involved in transcriptional regulation. |
| Q5TZA2 | CROCC | S483 | ochoa | Rootletin (Ciliary rootlet coiled-coil protein) | Major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus (By similarity). Furthermore, is required for the correct positioning of the cilium basal body relative to the cell nucleus, to allow for ciliogenesis (PubMed:27623382). Contributes to centrosome cohesion before mitosis (PubMed:16203858). {ECO:0000250|UniProtKB:Q8CJ40, ECO:0000269|PubMed:16203858, ECO:0000269|PubMed:27623382}. |
| Q5U3C3 | TMEM164 | S74 | ochoa | Transmembrane protein 164 (Arachidonoyl ether phospholipid synthase) | Positive regulator of ferroptosis (PubMed:35947500, PubMed:36782012). Involved in the acylation of ether lysophospholipids with the arachidonoyl chain (5Z,8Z,11Z,14Z-eicosatetraenoyl; C20:4) of diacylglycerophospholipids, generating C20:4 ether glycerophospholipids (ePEs) such as 1-(1Z-octadecenyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine (PE (P-18:0/20:4)), which promotes ferroptosis (PubMed:36782012). Selectively mediates ATG5-dependent autophagosome formation during ferroptosis, rather than during starvation, and regulates the degradation of ferritin, GPX4 and lipid droplets to increase iron accumulation and lipid peroxidation, thereby promoting ferroptotic cell death (PubMed:35947500). {ECO:0000269|PubMed:35947500, ECO:0000269|PubMed:36782012}. |
| Q5U651 | RASIP1 | S188 | ochoa | Ras-interacting protein 1 (Rain) | Required for the proper formation of vascular structures that develop via both vasculogenesis and angiogenesis. Acts as a critical and vascular-specific regulator of GTPase signaling, cell architecture, and adhesion, which is essential for endothelial cell morphogenesis and blood vessel tubulogenesis. Regulates the activity of Rho GTPases in part by recruiting ARHGAP29 and suppressing RhoA signaling and dampening ROCK and MYH9 activities in endothelial cells (By similarity). May act as effector for Golgi-bound HRAS and other Ras-like proteins. May promote HRAS-mediated transformation. Negative regulator of amino acid starvation-induced autophagy. {ECO:0000250, ECO:0000269|PubMed:15031288, ECO:0000269|PubMed:22354037}. |
| Q5UIP0 | RIF1 | S1230 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5UIP0 | RIF1 | S1564 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5VSY0 | GKAP1 | S25 | ochoa | G kinase-anchoring protein 1 (cGMP-dependent protein kinase-anchoring protein of 42 kDa) | Regulates insulin-dependent IRS1 tyrosine phosphorylation in adipocytes by modulating the availability of IRS1 to IR tyrosine kinase. Its association with IRS1 is required for insulin-induced translocation of SLC2A4 to the cell membrane. Involved in TNF-induced impairment of insulin-dependent IRS1 tyrosine phosphorylation. {ECO:0000250|UniProtKB:Q9JMB0}. |
| Q5VSY0 | GKAP1 | S27 | ochoa | G kinase-anchoring protein 1 (cGMP-dependent protein kinase-anchoring protein of 42 kDa) | Regulates insulin-dependent IRS1 tyrosine phosphorylation in adipocytes by modulating the availability of IRS1 to IR tyrosine kinase. Its association with IRS1 is required for insulin-induced translocation of SLC2A4 to the cell membrane. Involved in TNF-induced impairment of insulin-dependent IRS1 tyrosine phosphorylation. {ECO:0000250|UniProtKB:Q9JMB0}. |
| Q5VT25 | CDC42BPA | S1654 | ochoa | Serine/threonine-protein kinase MRCK alpha (EC 2.7.11.1) (CDC42-binding protein kinase alpha) (DMPK-like alpha) (Myotonic dystrophy kinase-related CDC42-binding kinase alpha) (MRCK alpha) (Myotonic dystrophy protein kinase-like alpha) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration (PubMed:15723050, PubMed:9092543, PubMed:9418861). Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates: PPP1R12A, LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in TFRC-mediated iron uptake (PubMed:20188707). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). Triggers the formation of an extrusion apical actin ring required for epithelial extrusion of apoptotic cells (PubMed:29162624). {ECO:0000250|UniProtKB:Q3UU96, ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11399775, ECO:0000269|PubMed:15723050, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:20188707, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:29162624, ECO:0000269|PubMed:9092543, ECO:0000269|PubMed:9418861}. |
| Q5VUA4 | ZNF318 | S173 | ochoa | Zinc finger protein 318 (Endocrine regulatory protein) | [Isoform 2]: Acts as a transcriptional corepressor for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}.; FUNCTION: [Isoform 1]: Acts as a transcriptional coactivator for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}. |
| Q5VUB5 | FAM171A1 | S511 | ochoa | Protein FAM171A1 (Astroprincin) (APCN) | Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation. {ECO:0000269|PubMed:30312582}. |
| Q5VWJ9 | SNX30 | S27 | ochoa | Sorting nexin-30 | Involved in the regulation of endocytosis and in several stages of intracellular trafficking (PubMed:32513819). Together with SNX4, involved in autophagosome assembly (PubMed:32513819). {ECO:0000269|PubMed:32513819}. |
| Q5VWQ8 | DAB2IP | S851 | ochoa | Disabled homolog 2-interacting protein (DAB2 interaction protein) (DAB2-interacting protein) (ASK-interacting protein 1) (AIP-1) (DOC-2/DAB-2 interactive protein) | Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Also plays a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to pro-inflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Also mediates TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6), Ras and RAB40C (PubMed:29156729). Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Also functions as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively. {ECO:0000269|PubMed:12813029, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:18292600, ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930, ECO:0000269|PubMed:22696229, ECO:0000269|PubMed:29156729}. |
| Q5VYS4 | MEDAG | S264 | ochoa | Mesenteric estrogen-dependent adipogenesis protein (Activated in W/Wv mouse stomach 3 homolog) (hAWMS3) (Mesenteric estrogen-dependent adipose 4) (MEDA-4) | Involved in processes that promote adipocyte differentiation, lipid accumulation, and glucose uptake in mature adipocytes. {ECO:0000250}. |
| Q5VZL5 | ZMYM4 | S1249 | ochoa | Zinc finger MYM-type protein 4 (Zinc finger protein 262) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q5XKK7 | FAM219B | S133 | ochoa | Protein FAM219B | None |
| Q5ZPR3 | CD276 | S513 | ochoa | CD276 antigen (4Ig-B7-H3) (B7 homolog 3) (B7-H3) (Costimulatory molecule) (CD antigen CD276) | May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling. {ECO:0000269|PubMed:11224528, ECO:0000269|PubMed:12906861, ECO:0000269|PubMed:14764704, ECO:0000269|PubMed:15314238, ECO:0000269|PubMed:15682454, ECO:0000269|PubMed:15961727}. |
| Q641Q2 | WASHC2A | S356 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q641Q2 | WASHC2A | S925 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q641Q2 | WASHC2A | S1008 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q641Q2 | WASHC2A | S1142 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q66K14 | TBC1D9B | S427 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q66K14 | TBC1D9B | S1132 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q66K74 | MAP1S | S478 | ochoa | Microtubule-associated protein 1S (MAP-1S) (BPY2-interacting protein 1) (Microtubule-associated protein 8) (Variable charge Y chromosome 2-interacting protein 1) (VCY2-interacting protein 1) (VCY2IP-1) [Cleaved into: MAP1S heavy chain; MAP1S light chain] | Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles (By similarity). {ECO:0000250, ECO:0000269|PubMed:15899810, ECO:0000269|PubMed:17234756}. |
| Q68CP4 | HGSNAT | S243 | ochoa | Heparan-alpha-glucosaminide N-acetyltransferase (EC 2.3.1.78) (Transmembrane protein 76) | Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase. {ECO:0000269|PubMed:16960811, ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20650889}. |
| Q68CZ2 | TNS3 | S649 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q68CZ2 | TNS3 | S725 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q68CZ2 | TNS3 | S963 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q68DQ2 | CRYBG3 | S340 | ochoa | Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) | [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}. |
| Q68DQ2 | CRYBG3 | S445 | ochoa | Very large A-kinase anchor protein (vlAKAP) (Beta/gamma crystallin domain-containing protein 3) | [Isoform vlAKAP]: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA). {ECO:0000269|PubMed:25097019}. |
| Q69YH5 | CDCA2 | S286 | ochoa | Cell division cycle-associated protein 2 (Recruits PP1 onto mitotic chromatin at anaphase protein) (Repo-Man) | Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phopsphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates. {ECO:0000269|PubMed:16492807, ECO:0000269|PubMed:16998479}. |
| Q6A1A2 | PDPK2P | S37 | ochoa | Putative 3-phosphoinositide-dependent protein kinase 2 (EC 2.7.11.1) (3-phosphoinositide-dependent protein kinase 2 pseudogene) | Phosphorylates and activates not only PKB/AKT, but also PKA, PKC-zeta, RPS6KA1 and RPS6KB1. May play a general role in signaling processes and in development (By similarity). {ECO:0000250}. |
| Q6AI08 | HEATR6 | S672 | ochoa | HEAT repeat-containing protein 6 (Amplified in breast cancer protein 1) | Amplification-dependent oncogene. |
| Q6DCA0 | AMMECR1L | S29 | ochoa | AMMECR1-like protein | None |
| Q6DT37 | CDC42BPG | S1475 | ochoa | Serine/threonine-protein kinase MRCK gamma (EC 2.7.11.1) (CDC42-binding protein kinase gamma) (DMPK-like gamma) (Myotonic dystrophy kinase-related CDC42-binding kinase gamma) (MRCK gamma) (MRCKG) (Myotonic dystrophy protein kinase-like gamma) (Myotonic dystrophy protein kinase-like alpha) | May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation (By similarity). {ECO:0000250|UniProtKB:Q5VT25, ECO:0000269|PubMed:15194684}. |
| Q6GQQ9 | OTUD7B | S60 | ochoa | OTU domain-containing protein 7B (EC 3.4.19.12) (Cellular zinc finger anti-NF-kappa-B protein) (Cezanne) (Zinc finger A20 domain-containing protein 1) (Zinc finger protein Cezanne) | Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses (PubMed:18178551). In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (By similarity). Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:11463333, PubMed:20622874, PubMed:23827681, PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin (PubMed:12682062). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked deubiquitination of MLST8, thereby promoting assembly of the mTORC2 complex, while inibiting formation of the mTORC1 complex (PubMed:28489822). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584, ECO:0000269|PubMed:28489822}. |
| Q6GYQ0 | RALGAPA1 | S740 | ochoa | Ral GTPase-activating protein subunit alpha-1 (GAP-related-interacting partner to E12) (GRIPE) (GTPase-activating Rap/Ran-GAP domain-like 1) (Tuberin-like protein 1) (p240) | Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q6H8Q1 | ABLIM2 | S370 | ochoa | Actin-binding LIM protein 2 (abLIM-2) (Actin-binding LIM protein family member 2) | May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity. {ECO:0000269|PubMed:17194709}. |
| Q6IWH7 | ANO7 | S81 | ochoa | Anoctamin-7 (Dresden transmembrane protein of the prostate) (D-TMPP) (IPCA-5) (New gene expressed in prostate) (Prostate cancer-associated protein 5) (Transmembrane protein 16G) | Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (By similarity). Does not exhibit calcium-activated chloride channel (CaCC) activity (PubMed:22075693). May play a role in cell-cell interactions (PubMed:17308099). {ECO:0000250|UniProtKB:Q14AT5, ECO:0000269|PubMed:17308099, ECO:0000269|PubMed:22075693}. |
| Q6KC79 | NIPBL | S1042 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6NSJ2 | PHLDB3 | S63 | ochoa | Pleckstrin homology-like domain family B member 3 | None |
| Q6P1M3 | LLGL2 | S1000 | ochoa | LLGL scribble cell polarity complex component 2 (HGL) (Lethal(2) giant larvae protein homolog 2) | Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity. {ECO:0000269|PubMed:15632202}. |
| Q6P435 | None | S90 | ochoa | Putative uncharacterized SMG1-like protein | None |
| Q6P474 | PDXDC2P | S400 | ochoa | Putative pyridoxal-dependent decarboxylase domain-containing protein 2 (EC 4.1.1.-) (pyridoxal-dependent decarboxylase domain-containing 2 pseudogene) | None |
| Q6P996 | PDXDC1 | S401 | ochoa | Pyridoxal-dependent decarboxylase domain-containing protein 1 (EC 4.1.1.-) | None |
| Q6PI98 | INO80C | S32 | ochoa | INO80 complex subunit C (IES6 homolog) (hIes6) | Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. |
| Q6PJT7 | ZC3H14 | S327 | ochoa | Zinc finger CCCH domain-containing protein 14 (Mammalian suppressor of tau pathology-2) (MSUT-2) (Renal carcinoma antigen NY-REN-37) | RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs (PubMed:39461343). Acts by binding to both exon-intron boundary and 3'-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome (PubMed:39461343). Required for spermatogenesis via involvement in circRNA biogenesis (PubMed:39461343). Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation (PubMed:27563065). Also binds the poly(A) tail of mRNAs; controlling poly(A) length in neuronal cells (PubMed:17630287, PubMed:24671764). {ECO:0000269|PubMed:17630287, ECO:0000269|PubMed:24671764, ECO:0000269|PubMed:27563065, ECO:0000269|PubMed:39461343}. |
| Q6PKG0 | LARP1 | S165 | ochoa | La-related protein 1 (La ribonucleoprotein domain family member 1) | RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability (PubMed:20430826, PubMed:23711370, PubMed:24532714, PubMed:25940091, PubMed:28650797, PubMed:28673543, PubMed:29244122). Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:23711370, PubMed:25940091, PubMed:26206669, PubMed:28379136, PubMed:28650797, PubMed:29244122). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1 (PubMed:25940091, PubMed:28379136, PubMed:28650797, PubMed:29244122). When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA (PubMed:25940091, PubMed:28650797). Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif (PubMed:28379136). Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:28673543). Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis (PubMed:23711370, PubMed:28650797). Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:20430826, PubMed:24532714). Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis (PubMed:20430826, PubMed:23711370, PubMed:25940091, PubMed:28673543). {ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:23711370, ECO:0000269|PubMed:24532714, ECO:0000269|PubMed:25940091, ECO:0000269|PubMed:26206669, ECO:0000269|PubMed:28379136, ECO:0000269|PubMed:28650797, ECO:0000269|PubMed:28673543, ECO:0000269|PubMed:29244122}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| Q6PKG0 | LARP1 | S861 | ochoa | La-related protein 1 (La ribonucleoprotein domain family member 1) | RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability (PubMed:20430826, PubMed:23711370, PubMed:24532714, PubMed:25940091, PubMed:28650797, PubMed:28673543, PubMed:29244122). Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:23711370, PubMed:25940091, PubMed:26206669, PubMed:28379136, PubMed:28650797, PubMed:29244122). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1 (PubMed:25940091, PubMed:28379136, PubMed:28650797, PubMed:29244122). When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA (PubMed:25940091, PubMed:28650797). Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif (PubMed:28379136). Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:28673543). Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis (PubMed:23711370, PubMed:28650797). Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:20430826, PubMed:24532714). Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis (PubMed:20430826, PubMed:23711370, PubMed:25940091, PubMed:28673543). {ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:23711370, ECO:0000269|PubMed:24532714, ECO:0000269|PubMed:25940091, ECO:0000269|PubMed:26206669, ECO:0000269|PubMed:28379136, ECO:0000269|PubMed:28650797, ECO:0000269|PubMed:28673543, ECO:0000269|PubMed:29244122}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| Q6R327 | RICTOR | S1174 | ochoa | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6R327 | RICTOR | S1292 | ochoa | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6RW13 | AGTRAP | S126 | ochoa | Type-1 angiotensin II receptor-associated protein (AT1 receptor-associated protein) | Appears to be a negative regulator of type-1 angiotensin II receptor-mediated signaling by regulating receptor internalization as well as mechanism of receptor desensitization such as phosphorylation. Also induces a decrease in cell proliferation and angiotensin II-stimulated transcriptional activity. {ECO:0000269|PubMed:12960423}. |
| Q6SPF0 | SAMD1 | S261 | ochoa | Sterile alpha motif domain-containing protein 1 (SAM domain-containing protein 1) (Atherin) | Unmethylated CpG islands (CGIs)-binding protein which localizes to H3K4me3-decorated CGIs, where it acts as a transcriptional repressor (PubMed:33980486). Tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs (PubMed:33980486). Plays a role in atherogenesis by binding with LDL on cell surface and promoting LDL oxidation which leads to the formation of foam cell (PubMed:16159594, PubMed:34006929). {ECO:0000269|PubMed:16159594, ECO:0000269|PubMed:33980486, ECO:0000269|PubMed:34006929}. |
| Q6UXK2 | ISLR2 | S717 | ochoa | Immunoglobulin superfamily containing leucine-rich repeat protein 2 (Leucine-rich repeat domain and immunoglobulin domain-containing axon extension protein) | Required for axon extension during neural development. {ECO:0000250}. |
| Q6VY07 | PACS1 | S417 | ochoa | Phosphofurin acidic cluster sorting protein 1 (PACS-1) | Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin-coated membrane pits. Involved in HIV-1 nef-mediated removal of MHC-I from the cell surface to the TGN. Required for normal ER Ca2+ handling in lymphocytes. Together with WDR37, it plays an essential role in lymphocyte development, quiescence and survival. Required for stabilizing peripheral lymphocyte populations (By similarity). {ECO:0000250|UniProtKB:Q8K212, ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:15692563}. |
| Q6W2J9 | BCOR | S473 | ochoa | BCL-6 corepressor (BCoR) | Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as BCL6 and MLLT3. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor. Involved in the repression of TFAP2A; impairs binding of BCL6 and KDM2B to TFAP2A promoter regions. Via repression of TFAP2A acts as a negative regulator of osteo-dentiogenic capacity in adult stem cells; the function implies inhibition of methylation on histone H3 'Lys-4' (H3K4me3) and 'Lys-36' (H3K36me2). {ECO:0000269|PubMed:10898795, ECO:0000269|PubMed:15004558, ECO:0000269|PubMed:18280243, ECO:0000269|PubMed:19578371, ECO:0000269|PubMed:23911289}. |
| Q6WKZ4 | RAB11FIP1 | S1171 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6XZF7 | DNMBP | S436 | ochoa | Dynamin-binding protein (Scaffold protein Tuba) | Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells (PubMed:17015620, PubMed:19767742). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (PubMed:20479467). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (By similarity). {ECO:0000250|UniProtKB:E2RP94, ECO:0000250|UniProtKB:Q6TXD4, ECO:0000269|PubMed:17015620, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20479467}. |
| Q6Y7W6 | GIGYF2 | S277 | ochoa | GRB10-interacting GYF protein 2 (PERQ amino acid-rich with GYF domain-containing protein 2) (Trinucleotide repeat-containing gene 15 protein) | Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931, PubMed:31439631, PubMed:35878012). In the 4EHP-GYF2 complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (PubMed:31439631). Also recruits and bridges the association of the 4EHP complex with the decapping effector protein DDX6, which is required for the ZFP36/TTP-mediated down-regulation of AU-rich mRNA (PubMed:31439631). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153). In association with EIF4E2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide (PubMed:32726578). GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist (PubMed:32726578). {ECO:0000269|PubMed:12771153, ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:31439631, ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:35878012}.; FUNCTION: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 infection, the interaction with non-structural protein 2 (nsp2) enhances GIGYF2 binding to EIF4E2 and increases repression of translation initiation of genes involved in antiviral innate immune response such as IFNB1. {ECO:0000269|PubMed:35878012}. |
| Q6ZNA4 | RNF111 | S579 | ochoa | E3 ubiquitin-protein ligase Arkadia (EC 2.3.2.27) (RING finger protein 111) (hRNF111) (RING-type E3 ubiquitin transferase Arkadia) | E3 ubiquitin-protein ligase (PubMed:26656854). Required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP (PubMed:14657019, PubMed:16601693). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (PubMed:14657019, PubMed:16601693). In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors 'in use' are degraded (By similarity). Activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL (PubMed:17591695). Associates with UBE2D2 as an E2 enzyme (PubMed:22411132). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (PubMed:23751493). Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair (PubMed:23751493). Mediates ubiquitination and degradation of sumoylated PML (By similarity). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By similarity). {ECO:0000250|UniProtKB:Q99ML9, ECO:0000269|PubMed:14657019, ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17591695, ECO:0000269|PubMed:22411132, ECO:0000269|PubMed:23751493, ECO:0000269|PubMed:26656854}. |
| Q6ZNA4 | RNF111 | S581 | ochoa | E3 ubiquitin-protein ligase Arkadia (EC 2.3.2.27) (RING finger protein 111) (hRNF111) (RING-type E3 ubiquitin transferase Arkadia) | E3 ubiquitin-protein ligase (PubMed:26656854). Required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP (PubMed:14657019, PubMed:16601693). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (PubMed:14657019, PubMed:16601693). In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors 'in use' are degraded (By similarity). Activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL (PubMed:17591695). Associates with UBE2D2 as an E2 enzyme (PubMed:22411132). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (PubMed:23751493). Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair (PubMed:23751493). Mediates ubiquitination and degradation of sumoylated PML (By similarity). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By similarity). {ECO:0000250|UniProtKB:Q99ML9, ECO:0000269|PubMed:14657019, ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17591695, ECO:0000269|PubMed:22411132, ECO:0000269|PubMed:23751493, ECO:0000269|PubMed:26656854}. |
| Q6ZNB6 | NFXL1 | S69 | ochoa | NF-X1-type zinc finger protein NFXL1 (Ovarian zinc finger protein) (hOZFP) | None |
| Q6ZNJ1 | NBEAL2 | S1367 | ochoa | Neurobeachin-like protein 2 | Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}. |
| Q6ZRS2 | SRCAP | S568 | ochoa | Helicase SRCAP (EC 3.6.4.-) (Domino homolog 2) (Snf2-related CBP activator) | Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch-mediated transcription. {ECO:0000269|PubMed:10347196, ECO:0000269|PubMed:11522779, ECO:0000269|PubMed:14500758, ECO:0000269|PubMed:16024792, ECO:0000269|PubMed:16634648, ECO:0000269|PubMed:17617668}. |
| Q6ZRV2 | FAM83H | S523 | ochoa | Protein FAM83H | May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration (PubMed:23902688). {ECO:0000269|PubMed:18252228, ECO:0000269|PubMed:23902688}. |
| Q6ZRV2 | FAM83H | S647 | ochoa | Protein FAM83H | May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration (PubMed:23902688). {ECO:0000269|PubMed:18252228, ECO:0000269|PubMed:23902688}. |
| Q6ZRV2 | FAM83H | S828 | ochoa | Protein FAM83H | May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration (PubMed:23902688). {ECO:0000269|PubMed:18252228, ECO:0000269|PubMed:23902688}. |
| Q6ZS17 | RIPOR1 | S171 | ochoa | Rho family-interacting cell polarization regulator 1 | Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration (PubMed:27807006). Acts as an adapter protein, linking active Rho proteins to STK24 and STK26 kinases, and hence positively regulates Golgi reorientation in polarized cell migration upon Rho activation (PubMed:27807006). Involved in the subcellular relocation of STK26 from the Golgi to cytoplasm punctae in a Rho- and PDCD10-dependent manner upon serum stimulation (PubMed:27807006). {ECO:0000269|PubMed:27807006}. |
| Q6ZU35 | CRACD | S1143 | ochoa | Capping protein-inhibiting regulator of actin dynamics (Cancer-related regulator of actin dynamics) | Involved in epithelial cell integrity by acting on the maintenance of the actin cytoskeleton. Positively regulates the actin polymerization, by inhibiting the interaction of actin-capping proteins with actin. {ECO:0000269|PubMed:30361697}. |
| Q6ZUM4 | ARHGAP27 | S632 | ochoa | Rho GTPase-activating protein 27 (CIN85-associated multi-domain-containing Rho GTPase-activating protein 1) (Rho-type GTPase-activating protein 27) (SH3 domain-containing protein 20) | Rho GTPase-activating protein which may be involved in clathrin-mediated endocytosis. GTPase activators for the Rho-type GTPases act by converting them to an inactive GDP-bound state. Has activity toward CDC42 and RAC1 (By similarity). {ECO:0000250}. |
| Q6ZVF9 | GPRIN3 | S619 | ochoa | G protein-regulated inducer of neurite outgrowth 3 (GRIN3) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q6ZVL6 | KIAA1549L | S1581 | ochoa | UPF0606 protein KIAA1549L | None |
| Q709C8 | VPS13C | S3641 | ochoa | Intermembrane lipid transfer protein VPS13C (Vacuolar protein sorting-associated protein 13C) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential (PubMed:26942284). Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization (PubMed:26942284). {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:26942284}. |
| Q70J99 | UNC13D | S153 | ochoa | Protein unc-13 homolog D (Munc13-4) | Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells. {ECO:0000269|PubMed:15548590, ECO:0000269|PubMed:17237785}. |
| Q717R9 | CYS1 | S128 | ochoa | Cystin-1 (Cilia-associated protein) | None |
| Q71F23 | CENPU | S229 | ochoa | Centromere protein U (CENP-U) (Centromere protein of 50 kDa) (CENP-50) (Interphase centromere complex protein 24) (KSHV latent nuclear antigen-interacting protein 1) (MLF1-interacting protein) (Polo-box-interacting protein 1) | Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression. {ECO:0000269|PubMed:12941884, ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:17081991}. |
| Q71RC2 | LARP4 | S392 | ochoa | La-related protein 4 (La ribonucleoprotein domain family member 4) | RNA binding protein that binds to the poly-A tract of mRNA molecules (PubMed:21098120). Associates with the 40S ribosomal subunit and with polysomes (PubMed:21098120). Plays a role in the regulation of mRNA translation (PubMed:21098120). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987, PubMed:27615744). {ECO:0000269|PubMed:21098120, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:27615744}. |
| Q7KZI7 | MARK2 | S675 | ochoa | Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}. |
| Q7L5D6 | GET4 | S308 | ochoa | Golgi to ER traffic protein 4 homolog (Conserved edge-expressed protein) (Transmembrane domain recognition complex 35 kDa subunit) (TRC35) | As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892, PubMed:32395830). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:25535373, PubMed:28104892). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). {ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:28104892, ECO:0000269|PubMed:32395830}. |
| Q7L5N1 | COPS6 | S211 | ochoa | COP9 signalosome complex subunit 6 (SGN6) (Signalosome subunit 6) (JAB1-containing signalosome subunit 6) (MOV34 homolog) (Vpr-interacting protein) (hVIP) | Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Stabilizes COP1 through reducing COP1 auto-ubiquitination and decelerating COP1 turnover rate, hence regulates the ubiquitination of COP1 targets. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:21625211, ECO:0000269|PubMed:9535219}. |
| Q7L7X3 | TAOK1 | S172 | ochoa | Serine/threonine-protein kinase TAO1 (EC 2.7.11.1) (Kinase from chicken homolog B) (hKFC-B) (MARK Kinase) (MARKK) (Prostate-derived sterile 20-like kinase 2) (PSK-2) (PSK2) (Prostate-derived STE20-like kinase 2) (Thousand and one amino acid protein kinase 1) (TAOK1) (hTAOK1) | Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system (PubMed:33565190). Also plays a role in the regulation of neuronal migration to the cortical plate (By similarity). {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936, ECO:0000269|PubMed:33565190}. |
| Q7L9L4 | MOB1B | S38 | ochoa | MOB kinase activator 1B (Mob1 homolog 1A) (Mob1A) (Mob1B) (Mps one binder kinase activator-like 1A) | Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38L. {ECO:0000269|PubMed:15067004, ECO:0000269|PubMed:19739119}. |
| Q7RTP6 | MICAL3 | S870 | ochoa | [F-actin]-monooxygenase MICAL3 (EC 1.14.13.225) (Molecule interacting with CasL protein 3) (MICAL-3) | Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission. {ECO:0000269|PubMed:21596566, ECO:0000269|PubMed:24440334}. |
| Q7Z2K8 | GPRIN1 | S90 | ochoa | G protein-regulated inducer of neurite outgrowth 1 (GRIN1) | May be involved in neurite outgrowth. {ECO:0000250}. |
| Q7Z3J3 | RGPD4 | S1224 | ochoa | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q7Z417 | NUFIP2 | S212 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z417 | NUFIP2 | S637 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z417 | NUFIP2 | S655 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z460 | CLASP1 | S280 | ochoa | CLIP-associating protein 1 (Cytoplasmic linker-associated protein 1) (Multiple asters homolog 1) (Protein Orbit homolog 1) (hOrbit1) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}. |
| Q7Z460 | CLASP1 | S576 | ochoa | CLIP-associating protein 1 (Cytoplasmic linker-associated protein 1) (Multiple asters homolog 1) (Protein Orbit homolog 1) (hOrbit1) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}. |
| Q7Z460 | CLASP1 | S1232 | ochoa | CLIP-associating protein 1 (Cytoplasmic linker-associated protein 1) (Multiple asters homolog 1) (Protein Orbit homolog 1) (hOrbit1) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:12837247, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864}. |
| Q7Z4S6 | KIF21A | S864 | ochoa | Kinesin-like protein KIF21A (Kinesin-like protein KIF2) (Renal carcinoma antigen NY-REN-62) | Processive microtubule plus-end directed motor protein involved in neuronal axon guidance. Is recruited by KANK1 to cortical microtubule stabilizing complexes (CMSCs) at focal adhesions (FAs) rims where it promotes microtubule capture and stability. Controls microtubule polymerization rate at axonal growth cones and suppresses microtubule growth without inducing microtubule disassembly once it reaches the cell cortex. {ECO:0000250|UniProtKB:Q9QXL2, ECO:0000269|PubMed:24120883}. |
| Q7Z4V5 | HDGFL2 | S652 | ochoa | Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) | Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}. |
| Q7Z591 | AKNA | S1133 | ochoa | Microtubule organization protein AKNA (AT-hook-containing transcription factor) | Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (By similarity). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (By similarity). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (By similarity). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (By similarity). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (PubMed:11268217). Binds to A/T-rich promoters (PubMed:11268217). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable). {ECO:0000250|UniProtKB:Q80VW7, ECO:0000269|PubMed:11268217, ECO:0000305}. |
| Q7Z5J4 | RAI1 | S1374 | ochoa | Retinoic acid-induced protein 1 | Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}. |
| Q7Z5K2 | WAPL | S231 | ochoa | Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) | Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}. |
| Q7Z5K2 | WAPL | S443 | ochoa | Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) | Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}. |
| Q7Z5K2 | WAPL | S445 | ochoa | Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) | Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}. |
| Q7Z6E9 | RBBP6 | S1261 | ochoa | E3 ubiquitin-protein ligase RBBP6 (EC 2.3.2.27) (Proliferation potential-related protein) (Protein P2P-R) (RING-type E3 ubiquitin transferase RBBP6) (Retinoblastoma-binding Q protein 1) (RBQ-1) (Retinoblastoma-binding protein 6) (p53-associated cellular protein of testis) | E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome (PubMed:18851979). May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth (By similarity). Regulates DNA-replication and the stability of chromosomal common fragile sites (CFSs) in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication (PubMed:24726359). {ECO:0000250|UniProtKB:P97868, ECO:0000269|PubMed:18851979, ECO:0000269|PubMed:24726359}.; FUNCTION: (Microbial infection) [Isoform 1]: Restricts ebolavirus replication probably by impairing the vp30-NP interaction, and thus viral transcription. {ECO:0000269|PubMed:30550789}. |
| Q7Z6I6 | ARHGAP30 | S865 | ochoa | Rho GTPase-activating protein 30 (Rho-type GTPase-activating protein 30) | GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42. {ECO:0000269|PubMed:21565175}. |
| Q7Z6I6 | ARHGAP30 | S994 | ochoa | Rho GTPase-activating protein 30 (Rho-type GTPase-activating protein 30) | GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42. {ECO:0000269|PubMed:21565175}. |
| Q7Z6J0 | SH3RF1 | S551 | ochoa | E3 ubiquitin-protein ligase SH3RF1 (EC 2.3.2.27) (Plenty of SH3s) (Protein POSH) (RING finger protein 142) (RING-type E3 ubiquitin transferase SH3RF1) (SH3 domain-containing RING finger protein 1) (SH3 multiple domains protein 2) | Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity). {ECO:0000250|UniProtKB:Q69ZI1, ECO:0000269|PubMed:15659549, ECO:0000269|PubMed:19710010, ECO:0000269|PubMed:20696164}.; FUNCTION: (Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity. {ECO:0000269|PubMed:15659549}. |
| Q7Z6Z7 | HUWE1 | S1903 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S2887 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S3320 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S3752 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S3757 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z7G8 | VPS13B | S1798 | ochoa | Intermembrane lipid transfer protein VPS13B (Cohen syndrome protein 1) (Vacuolar protein sorting-associated protein 13B) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phosphatidylinositol 3-phosphate (By similarity). Functions as a tethering factor in the slow endocytic recycling pathway, to assist traffic between early and recycling endosomes (PubMed:24334764, PubMed:30962439, PubMed:32375900). Involved in the transport of proacrosomal vesicles to the nuclear dense lamina (NDL) during spermatid development (By similarity). Plays a role in the assembly of the Golgi apparatus, possibly by mediating trafficking to the Golgi membrane (PubMed:21865173). Plays a role in the development of the nervous system, and may be required for neuron projection development (PubMed:25492866, PubMed:32560273). May also play a role during adipose tissue development (PubMed:26358774). Required for maintenance of the ocular lens (By similarity). {ECO:0000250|UniProtKB:Q07878, ECO:0000250|UniProtKB:Q80TY5, ECO:0000269|PubMed:21865173, ECO:0000269|PubMed:24334764, ECO:0000269|PubMed:26358774, ECO:0000269|PubMed:30962439, ECO:0000269|PubMed:32375900, ECO:0000269|PubMed:32560273, ECO:0000305|PubMed:25492866, ECO:0000305|PubMed:32560273}. |
| Q86SQ0 | PHLDB2 | S387 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86T82 | USP37 | S213 | ochoa | Ubiquitin carboxyl-terminal hydrolase 37 (EC 3.4.19.12) (Deubiquitinating enzyme 37) (Ubiquitin thioesterase 37) (Ubiquitin-specific-processing protease 37) | Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response (PubMed:26299517, PubMed:27296872, PubMed:31911859, PubMed:34509474). Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872). Also plays an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability (PubMed:34509474). Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM (PubMed:34606619). Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM (PubMed:34606619). Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI (PubMed:31911859). Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination (PubMed:26299517). {ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:26299517, ECO:0000269|PubMed:27296872, ECO:0000269|PubMed:31911859, ECO:0000269|PubMed:34509474, ECO:0000269|PubMed:34606619}. |
| Q86TV6 | TTC7B | S657 | ochoa | Tetratricopeptide repeat protein 7B (TPR repeat protein 7B) (Tetratricopeptide repeat protein 7-like-1) (TPR repeat protein 7-like-1) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (PubMed:26571211). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:26571211}. |
| Q86U44 | METTL3 | S344 | ochoa | N(6)-adenosine-methyltransferase catalytic subunit METTL3 (EC 2.1.1.348) (Methyltransferase-like protein 3) (hMETTL3) (N(6)-adenosine-methyltransferase 70 kDa subunit) (MT-A70) | The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27281194, PubMed:27373337, PubMed:27627798, PubMed:28297716, PubMed:29348140, PubMed:29506078, PubMed:30428350, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27281194, PubMed:27373337, PubMed:27627798). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A also regulates circadian regulation of hepatic lipid metabolism (PubMed:30428350). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Also required for oogenesis (By similarity). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (PubMed:28297716). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (By similarity). Inhibits the type I interferon response by mediating m6A methylation of IFNB (PubMed:30559377). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist (PubMed:27602518). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation (PubMed:27117702). During human coronavirus SARS-CoV-2 infection, adds m6A modifications in SARS-CoV-2 RNA leading to decreased RIGI binding and subsequently dampening the sensing and activation of innate immune responses (PubMed:33961823). {ECO:0000250|UniProtKB:Q8C3P7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26321680, ECO:0000269|PubMed:26593424, ECO:0000269|PubMed:27117702, ECO:0000269|PubMed:27281194, ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:27627798, ECO:0000269|PubMed:28297716, ECO:0000269|PubMed:28637692, ECO:0000269|PubMed:29348140, ECO:0000269|PubMed:29506078, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:33961823, ECO:0000269|PubMed:9409616}. |
| Q86UE8 | TLK2 | S94 | ochoa | Serine/threonine-protein kinase tousled-like 2 (EC 2.7.11.1) (HsHPK) (PKU-alpha) (Tousled-like kinase 2) | Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470, PubMed:9427565). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}. |
| Q86UF2 | CTAGE6 | S656 | ochoa | cTAGE family member 6 (Protein cTAGE-6) | None |
| Q86UX7 | FERMT3 | S484 | ochoa|psp | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86V48 | LUZP1 | S57 | ochoa | Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) | F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}. |
| Q86VR2 | RETREG3 | S28 | ochoa | Reticulophagy regulator 3 | Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (PubMed:33826365). Required for collagen quality control in a LIR motif-dependent manner (By similarity). Mediates NRF1-enhanced neurite outgrowth (PubMed:26040720). {ECO:0000250|UniProtKB:Q9CQV4, ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:33826365, ECO:0000269|PubMed:34338405}. |
| Q86W50 | METTL16 | S483 | ochoa | RNA N(6)-adenosine-methyltransferase METTL16 (EC 2.1.1.348) (Methyltransferase 10 domain-containing protein) (Methyltransferase-like protein 16) (U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase) (EC 2.1.1.346) | RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753, PubMed:30197297, PubMed:30197299, PubMed:33428944, PubMed:33930289). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753, PubMed:30197297, PubMed:30197299). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (PubMed:28525753, PubMed:33930289). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200, PubMed:32266935). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311). {ECO:0000269|PubMed:27872311, ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:29051200, ECO:0000269|PubMed:30197297, ECO:0000269|PubMed:30197299, ECO:0000269|PubMed:32266935, ECO:0000269|PubMed:33428944}. |
| Q86WP2 | GPBP1 | S322 | ochoa | Vasculin (GC-rich promoter-binding protein 1) (Vascular wall-linked protein) | Functions as a GC-rich promoter-specific transactivating transcription factor. {ECO:0000250|UniProtKB:Q6NXH3}. |
| Q86WR7 | PROSER2 | S31 | ochoa | Proline and serine-rich protein 2 | None |
| Q86X29 | LSR | S579 | ochoa | Lipolysis-stimulated lipoprotein receptor (Angulin-1) | Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (By similarity). Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (By similarity). {ECO:0000250|UniProtKB:Q99KG5, ECO:0000250|UniProtKB:Q9WU74}. |
| Q86XL3 | ANKLE2 | S512 | ochoa | Ankyrin repeat and LEM domain-containing protein 2 (LEM domain-containing protein 4) | Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit (PubMed:22770216). Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly (PubMed:22770216). May regulate nuclear localization of VRK1 in non-dividing cells (PubMed:31735666). It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex (PubMed:22770216). Involved in brain development (PubMed:25259927). {ECO:0000269|PubMed:22770216, ECO:0000269|PubMed:25259927, ECO:0000269|PubMed:31735666}. |
| Q86XL3 | ANKLE2 | S905 | ochoa | Ankyrin repeat and LEM domain-containing protein 2 (LEM domain-containing protein 4) | Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit (PubMed:22770216). Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly (PubMed:22770216). May regulate nuclear localization of VRK1 in non-dividing cells (PubMed:31735666). It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex (PubMed:22770216). Involved in brain development (PubMed:25259927). {ECO:0000269|PubMed:22770216, ECO:0000269|PubMed:25259927, ECO:0000269|PubMed:31735666}. |
| Q86YP4 | GATAD2A | S185 | ochoa | Transcriptional repressor p66-alpha (Hp66alpha) (GATA zinc finger domain-containing protein 2A) | Transcriptional repressor (PubMed:12183469, PubMed:16415179). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, PubMed:16415179). Efficient repression requires the presence of GATAD2B (PubMed:16415179). {ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:16415179, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| Q86YS7 | C2CD5 | S321 | ochoa | C2 domain-containing protein 5 (C2 domain-containing phosphoprotein of 138 kDa) | Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM. {ECO:0000269|PubMed:21907143}. |
| Q86YS7 | C2CD5 | S323 | ochoa | C2 domain-containing protein 5 (C2 domain-containing phosphoprotein of 138 kDa) | Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM. {ECO:0000269|PubMed:21907143}. |
| Q86YT6 | MIB1 | S405 | ochoa | E3 ubiquitin-protein ligase MIB1 (EC 2.3.2.27) (DAPK-interacting protein 1) (DIP-1) (Mind bomb homolog 1) (RING-type E3 ubiquitin transferase MIB1) (Zinc finger ZZ type with ankyrin repeat domain protein 2) | E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. {ECO:0000250, ECO:0000269|PubMed:24121310}.; FUNCTION: (Microbial infection) During adenovirus infection, mediates ubiquitination of Core-capsid bridging protein. This allows viral genome delivery into nucleus for infection. {ECO:0000269|PubMed:31851912}. |
| Q86YV0 | RASAL3 | S841 | ochoa | RAS protein activator like-3 | Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway. {ECO:0000250|UniProtKB:Q8C2K5}. |
| Q86YV5 | PRAG1 | S759 | ochoa | Inactive tyrosine-protein kinase PRAG1 (PEAK1-related kinase-activating pseudokinase 1) (Pragmin) (Sugen kinase 223) (SgK223) | Catalytically inactive protein kinase that acts as a scaffold protein. Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (By similarity). Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (By similarity). Acts as a critical coactivator of Notch signaling (By similarity). {ECO:0000250|UniProtKB:D3ZMK9, ECO:0000250|UniProtKB:Q571I4}. |
| Q86YV5 | PRAG1 | S889 | ochoa | Inactive tyrosine-protein kinase PRAG1 (PEAK1-related kinase-activating pseudokinase 1) (Pragmin) (Sugen kinase 223) (SgK223) | Catalytically inactive protein kinase that acts as a scaffold protein. Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (By similarity). Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (By similarity). Acts as a critical coactivator of Notch signaling (By similarity). {ECO:0000250|UniProtKB:D3ZMK9, ECO:0000250|UniProtKB:Q571I4}. |
| Q8IU81 | IRF2BP1 | S491 | ochoa | Interferon regulatory factor 2-binding protein 1 (IRF-2-binding protein 1) (IRF-2BP1) (Probable E3 ubiquitin-protein ligase IRF2BP1) (EC 2.3.2.27) (Probable RING-type E3 ubiquitin transferase IRF2BP1) | Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities. May act as an E3 ligase towards JDP2, enhancing its polyubiquitination. Represses ATF2-dependent transcriptional activation. {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:18671972}. |
| Q8IV31 | TMEM139 | S149 | ochoa | Transmembrane protein 139 | May be involved in cellular trafficking of proteins such as SLC4A1. {ECO:0000305|PubMed:26049106}. |
| Q8IV36 | HID1 | S593 | ochoa | Protein HID1 (Down-regulated in multiple cancers 1) (HID1 domain-containing protein) (Protein hid-1 homolog) | May play an important role in the development of cancers in a broad range of tissues. {ECO:0000269|PubMed:11281419}. |
| Q8IV45 | UNC5CL | S498 | ochoa | UNC5C-like protein (Protein unc-5 homolog C-like) (ZU5 and death domain-containing protein) | Inhibits NF-kappa-B-dependent transcription by impairing NF-kappa-B binding to its targets. {ECO:0000269|PubMed:14769797}. |
| Q8IVF2 | AHNAK2 | S332 | ochoa | Protein AHNAK2 | None |
| Q8IVT2 | MISP | S278 | ochoa | Mitotic interactor and substrate of PLK1 (Mitotic spindle positioning protein) | Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytospkeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus. {ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:23574715}. |
| Q8IVT5 | KSR1 | S194 | ochoa | Kinase suppressor of Ras 1 (EC 2.7.11.1) | Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (PubMed:29433126). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (By similarity). Its kinase activity is unsure (By similarity). Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (By similarity). {ECO:0000250|UniProtKB:Q61097, ECO:0000269|PubMed:29433126}. |
| Q8IVW6 | ARID3B | S63 | ochoa | AT-rich interactive domain-containing protein 3B (ARID domain-containing protein 3B) (Bright and dead ringer protein) (Bright-like protein) | Transcription factor which may be involved in neuroblastoma growth and malignant transformation. Favors nuclear targeting of ARID3A. {ECO:0000269|PubMed:16951138, ECO:0000269|PubMed:17400556}. |
| Q8IWQ3 | BRSK2 | S393 | ochoa | Serine/threonine-protein kinase BRSK2 (EC 2.7.11.1) (Brain-selective kinase 2) (EC 2.7.11.26) (Brain-specific serine/threonine-protein kinase 2) (BR serine/threonine-protein kinase 2) (Serine/threonine-protein kinase 29) (Serine/threonine-protein kinase SAD-A) | Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:22798068, ECO:0000269|PubMed:23029325}. |
| Q8IWX8 | CHERP | S828 | ochoa | Calcium homeostasis endoplasmic reticulum protein (ERPROT 213-21) (SR-related CTD-associated factor 6) | Involved in calcium homeostasis, growth and proliferation. {ECO:0000269|PubMed:10794731, ECO:0000269|PubMed:12656674}. |
| Q8IWZ3 | ANKHD1 | S887 | ochoa | Ankyrin repeat and KH domain-containing protein 1 (HIV-1 Vpr-binding ankyrin repeat protein) (Multiple ankyrin repeats single KH domain) (hMASK) | May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}. |
| Q8IXJ6 | SIRT2 | S53 | ochoa | NAD-dependent protein deacetylase sirtuin-2 (EC 2.3.1.286) (NAD-dependent protein defatty-acylase sirtuin-2) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 2) (SIR2-like protein 2) | NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20543840, PubMed:20587414, PubMed:21081649, PubMed:21726808, PubMed:21949390, PubMed:22014574, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24177535, PubMed:24681946, PubMed:24769394, PubMed:24940000). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy (PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20543840, PubMed:20587414, PubMed:21081649, PubMed:21726808, PubMed:21949390, PubMed:22014574, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24177535, PubMed:24681946, PubMed:24769394, PubMed:24940000). Plays a major role in the control of cell cycle progression and genomic stability (PubMed:12697818, PubMed:16909107, PubMed:17488717, PubMed:17726514, PubMed:19282667, PubMed:23468428). Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes (PubMed:12697818, PubMed:16909107, PubMed:17488717, PubMed:17726514, PubMed:19282667, PubMed:23468428). Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis (PubMed:22014574). Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes (PubMed:23468428). Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis (PubMed:23468428). Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). Also deacetylates histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition (PubMed:20587414). Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection (PubMed:23908241). During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function (PubMed:24940000). Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells (PubMed:18332217, PubMed:18995842). Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation (PubMed:17488717). Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination (PubMed:21949390). Involved in several cellular metabolic pathways (PubMed:20543840, PubMed:21726808, PubMed:24769394). Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability (PubMed:21726808). Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage (PubMed:24769394). Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis (PubMed:20543840). Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity (PubMed:20543840). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed:20543840). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:20543840). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation (PubMed:21081649). Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187, PubMed:18995842). Also deacetylates EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions (PubMed:24769394). Plays a role as tumor suppressor (PubMed:22014574). In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes (PubMed:25704306, PubMed:29239724, PubMed:32103017). {ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:17488717, ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:18640115, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:18995842, ECO:0000269|PubMed:19282667, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:20587414, ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:22771473, ECO:0000269|PubMed:22819792, ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24681946, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25704306, ECO:0000269|PubMed:29239724, ECO:0000269|PubMed:32103017}.; FUNCTION: [Isoform 1]: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.; FUNCTION: [Isoform 2]: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.; FUNCTION: [Isoform 5]: Lacks deacetylation activity, at least toward known SIRT2 targets. {ECO:0000269|PubMed:24177535}. |
| Q8IXT5 | RBM12B | S98 | ochoa | RNA-binding protein 12B (RNA-binding motif protein 12B) | None |
| Q8IY63 | AMOTL1 | S724 | ochoa | Angiomotin-like protein 1 | Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. {ECO:0000269|PubMed:22362771}. |
| Q8IYI6 | EXOC8 | S151 | ochoa | Exocyst complex component 8 (Exocyst complex 84 kDa subunit) | Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. |
| Q8IZD0 | SAMD14 | S64 | ochoa | Sterile alpha motif domain-containing protein 14 (SAM domain-containing protein 14) | None |
| Q8IZL8 | PELP1 | S485 | ochoa | Proline-, glutamic acid- and leucine-rich protein 1 (Modulator of non-genomic activity of estrogen receptor) (Transcription factor HMX3) | Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors (PubMed:14963108). Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Functions as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. Regulates pre-60S association of the critical remodeling factor MDN1 (PubMed:21326211). May promote tumorigenesis via its interaction with and modulation of several oncogenes including SRC, PI3K, STAT3 and EGFR. Plays a role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes and cell migration via its interaction with SRC and PI3K. {ECO:0000269|PubMed:11481323, ECO:0000269|PubMed:12682072, ECO:0000269|PubMed:14963108, ECO:0000269|PubMed:15374949, ECO:0000269|PubMed:15456770, ECO:0000269|PubMed:15579769, ECO:0000269|PubMed:15994929, ECO:0000269|PubMed:16140940, ECO:0000269|PubMed:16352611, ECO:0000269|PubMed:16574651, ECO:0000269|PubMed:21326211, ECO:0000269|PubMed:22872859}. |
| Q8IZL8 | PELP1 | S1073 | ochoa | Proline-, glutamic acid- and leucine-rich protein 1 (Modulator of non-genomic activity of estrogen receptor) (Transcription factor HMX3) | Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors (PubMed:14963108). Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Functions as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. Regulates pre-60S association of the critical remodeling factor MDN1 (PubMed:21326211). May promote tumorigenesis via its interaction with and modulation of several oncogenes including SRC, PI3K, STAT3 and EGFR. Plays a role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes and cell migration via its interaction with SRC and PI3K. {ECO:0000269|PubMed:11481323, ECO:0000269|PubMed:12682072, ECO:0000269|PubMed:14963108, ECO:0000269|PubMed:15374949, ECO:0000269|PubMed:15456770, ECO:0000269|PubMed:15579769, ECO:0000269|PubMed:15994929, ECO:0000269|PubMed:16140940, ECO:0000269|PubMed:16352611, ECO:0000269|PubMed:16574651, ECO:0000269|PubMed:21326211, ECO:0000269|PubMed:22872859}. |
| Q8IZQ1 | WDFY3 | S3328 | ochoa | WD repeat and FYVE domain-containing protein 3 (Autophagy-linked FYVE protein) (Alfy) | Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (PubMed:27008544). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By similarity). After cytokinetic abscission, involved in midbody remnant degradation (PubMed:24128730). In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400). {ECO:0000250|UniProtKB:Q6VNB8, ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27008544}. |
| Q8IZT6 | ASPM | S1105 | ochoa | Abnormal spindle-like microcephaly-associated protein (Abnormal spindle protein homolog) (Asp homolog) | Involved in mitotic spindle regulation and coordination of mitotic processes. The function in regulating microtubule dynamics at spindle poles including spindle orientation, astral microtubule density and poleward microtubule flux seems to depend on the association with the katanin complex formed by KATNA1 and KATNB1. Enhances the microtubule lattice severing activity of KATNA1 by recruiting the katanin complex to microtubules. Can block microtubule minus-end growth and reversely this function can be enhanced by the katanin complex (PubMed:28436967). May have a preferential role in regulating neurogenesis. {ECO:0000269|PubMed:12355089, ECO:0000269|PubMed:15972725, ECO:0000269|PubMed:28436967}. |
| Q8IZW8 | TNS4 | S269 | ochoa | Tensin-4 (C-terminal tensin-like protein) | Promotes EGF-induced cell migration by displacing tensin TNS3 from the cytoplasmic tail of integrin ITGB1 which results in dissociation of TNS3 from focal adhesions, disassembly of actin stress fibers and initiation of cell migration (PubMed:17643115). Suppresses ligand-induced degradation of EGFR by reducing EGFR ubiquitination in the presence of EGF (PubMed:23774213). Increases MET protein stability by inhibiting MET endocytosis and subsequent lysosomal degradation which leads to increased cell survival, proliferation and migration (PubMed:24814316). {ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:24814316}. |
| Q8N264 | ARHGAP24 | S437 | psp | Rho GTPase-activating protein 24 (Filamin-A-associated RhoGAP) (FilGAP) (RAC1- and CDC42-specific GTPase-activating protein of 72 kDa) (RC-GAP72) (Rho-type GTPase-activating protein 24) (RhoGAP of 73 kDa) (Sarcoma antigen NY-SAR-88) (p73RhoGAP) | Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis. {ECO:0000269|PubMed:15302923, ECO:0000269|PubMed:15611138, ECO:0000269|PubMed:16862148}. |
| Q8N2G6 | ZCCHC24 | S97 | ochoa | Zinc finger CCHC domain-containing protein 24 | None |
| Q8N370 | SLC43A2 | S277 | ochoa | Large neutral amino acids transporter small subunit 4 (L-type amino acid transporter 4) (Solute carrier family 43 member 2) | Uniporter that mediates the transport of the stereospecific L-phenylalanine, L-methionine and L-branched-chain amino acids, between the extracellular space and the cytoplasm and may control the transepithelial (re)absorption of neutral amino acid in kidney and small intestine (PubMed:15659399, PubMed:30379325). The transport activity is mediated through facilitated diffusion and is sodium ions-, chloride ions- and pH-independent (PubMed:15659399). {ECO:0000269|PubMed:15659399, ECO:0000269|PubMed:30379325}. |
| Q8N3D4 | EHBP1L1 | S462 | ochoa | EH domain-binding protein 1-like protein 1 | May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000305|PubMed:27552051}. |
| Q8N3J3 | HROB | S208 | ochoa | Homologous recombination OB-fold protein | DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis. {ECO:0000269|PubMed:31467087}. |
| Q8N3K9 | CMYA5 | S2686 | ochoa | Cardiomyopathy-associated protein 5 (Dystrobrevin-binding protein 2) (Genethonin-3) (Myospryn) (SPRY domain-containing protein 2) (Tripartite motif-containing protein 76) | May serve as an anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) via binding to PRKAR2A (By similarity). May function as a repressor of calcineurin-mediated transcriptional activity. May attenuate calcineurin ability to induce slow-fiber gene program in muscle and may negatively modulate skeletal muscle regeneration (By similarity). Plays a role in the assembly of ryanodine receptor (RYR2) clusters in striated muscle (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q70KF4}. |
| Q8N3S3 | PHTF2 | S221 | ochoa | Protein PHTF2 | None |
| Q8N4Y2 | CRACR2B | S174 | ochoa | EF-hand calcium-binding domain-containing protein 4A (Calcium release-activated calcium channel regulator 2B) (CRAC channel regulator 2B) (Calcium release-activated channel regulator 2B) | Plays a role in store-operated Ca(2+) entry (SOCE). {ECO:0000269|PubMed:20418871}. |
| Q8N567 | ZCCHC9 | S28 | ochoa | Zinc finger CCHC domain-containing protein 9 | May down-regulate transcription mediated by NF-kappa-B and the serum response element. {ECO:0000269|PubMed:18721783}. |
| Q8N5C8 | TAB3 | S492 | ochoa | TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 3) (NF-kappa-B-activating protein 1) (TAK1-binding protein 3) (TAB-3) (TGF-beta-activated kinase 1-binding protein 3) | Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122, PubMed:36593296). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:18079694, PubMed:22158122). {ECO:0000269|PubMed:14633987, ECO:0000269|PubMed:14766965, ECO:0000269|PubMed:15327770, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:36593296}.; FUNCTION: [Isoform 2]: May be an oncogenic factor. {ECO:0000269|PubMed:14766965}. |
| Q8N5H7 | SH2D3C | S338 | ochoa | SH2 domain-containing protein 3C (Cas/HEF1-associated signal transducer) (Chat-H) (Novel SH2-containing protein 3) (SH2 domain-containing Eph receptor-binding protein 1) (SHEP1) | Acts as an adapter protein that mediates cell signaling pathways involved in cellular functions such as cell adhesion and migration, tissue organization, and the regulation of the immune response (PubMed:12432078, PubMed:20881139). Plays a role in integrin-mediated cell adhesion through BCAR1-CRK-RAPGEF1 signaling and activation of the small GTPase RAP1 (PubMed:12432078). Promotes cell migration and invasion through the extracellular matrix (PubMed:20881139). Required for marginal zone B-cell development and thymus-independent type 2 immune responses (By similarity). Mediates migration and adhesion of B cells in the splenic marginal zone via promoting hyperphosphorylation of NEDD9/CASL (By similarity). Plays a role in CXCL13-induced chemotaxis of B-cells (By similarity). Plays a role in the migration of olfactory sensory neurons (OSNs) into the forebrain and the innervation of the olfactory bulb by the OSN axons during development (By similarity). Required for the efficient tyrosine phosphorylation of BCAR1 in OSN axons (By similarity). {ECO:0000250|UniProtKB:Q9QZS8, ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:20881139}.; FUNCTION: [Isoform 1]: Important regulator of chemokine-induced, integrin-mediated T lymphocyte adhesion and migration, acting upstream of RAP1 (By similarity). Required for tissue-specific adhesion of T lymphocytes to peripheral tissues (By similarity). Required for basal and CXCL2 stimulated serine-threonine phosphorylation of NEDD9 (By similarity). May be involved in the regulation of T-cell receptor-mediated IL2 production through the activation of the JNK pathway in T-cells (By similarity). {ECO:0000250|UniProtKB:Q9QZS8}.; FUNCTION: [Isoform 2]: May be involved in the BCAR1/CAS-mediated JNK activation pathway. {ECO:0000250|UniProtKB:Q9QZS8}. |
| Q8N6C5 | IGSF1 | S1294 | ochoa | Immunoglobulin superfamily member 1 (IgSF1) (Immunoglobulin-like domain-containing protein 1) (Inhibin-binding protein) (InhBP) (Pituitary gland-specific factor 2) (p120) | Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary to mediate a specific antagonistic effect of inhibin B on activin-stimulated transcription. {ECO:0000250, ECO:0000269|PubMed:11266516}. |
| Q8N6H7 | ARFGAP2 | S371 | ochoa | ADP-ribosylation factor GTPase-activating protein 2 (ARF GAP 2) (GTPase-activating protein ZNF289) (Zinc finger protein 289) | GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. {ECO:0000269|PubMed:17760859}. |
| Q8N8V4 | ANKS4B | S196 | ochoa | Ankyrin repeat and SAM domain-containing protein 4B (Harmonin-interacting ankyrin repeat-containing protein) (Harp) | As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. Plays a role in assembly of the complex (PubMed:26812018). May play a role in cellular response to endoplasmic reticulum stress (By similarity). {ECO:0000250|UniProtKB:Q8K3X6, ECO:0000269|PubMed:26812018}. |
| Q8N8Z6 | DCBLD1 | S492 | ochoa | Discoidin, CUB and LCCL domain-containing protein 1 | None |
| Q8N9T8 | KRI1 | S182 | ochoa | Protein KRI1 homolog | None |
| Q8NAN2 | MIGA1 | S147 | ochoa | Mitoguardin 1 (Protein FAM73A) | Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD. {ECO:0000269|PubMed:26711011}. |
| Q8NC24 | RELL2 | S187 | ochoa | RELT-like protein 2 | Induces activation of MAPK14/p38 cascade, when overexpressed (PubMed:28688764). Induces apoptosis, when overexpressed (PubMed:19969290). {ECO:0000269|PubMed:19969290, ECO:0000269|PubMed:28688764}. |
| Q8NC44 | RETREG2 | S145 | ochoa | Reticulophagy regulator 2 | Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Required for collagen quality control in a LIR motif-independent manner (By similarity). {ECO:0000250|UniProtKB:Q6NS82, ECO:0000269|PubMed:34338405}. |
| Q8NC51 | SERBP1 | S219 | ochoa | SERPINE1 mRNA-binding protein 1 (PAI1 RNA-binding protein 1) (PAI-RBP1) (Plasminogen activator inhibitor 1 RNA-binding protein) | Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:36691768). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (By similarity). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay (PubMed:11001948). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). {ECO:0000250|UniProtKB:Q9CY58, ECO:0000269|PubMed:11001948, ECO:0000269|PubMed:28695742, ECO:0000269|PubMed:36691768}. |
| Q8NC74 | RBBP8NL | S392 | ochoa | RBBP8 N-terminal-like protein | None |
| Q8NDX1 | PSD4 | S109 | ochoa | PH and SEC7 domain-containing protein 4 (Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 B) (Exchange factor for ARF6 B) (Pleckstrin homology and SEC7 domain-containing protein 4) (Telomeric of interleukin-1 cluster protein) | Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:12082148, ECO:0000269|PubMed:21458045}. |
| Q8NEY1 | NAV1 | S1369 | ochoa | Neuron navigator 1 (Pore membrane and/or filament-interacting-like protein 3) (Steerin-1) (Unc-53 homolog 1) (unc53H1) | May be involved in neuronal migration. {ECO:0000250}. |
| Q8NEZ4 | KMT2C | S1310 | ochoa | Histone-lysine N-methyltransferase 2C (Lysine N-methyltransferase 2C) (EC 2.1.1.364) (Homologous to ALR protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 3) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:22266653, PubMed:24081332, PubMed:25561738). Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements (PubMed:24081332). {ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q8NF50 | DOCK8 | S942 | ochoa | Dedicator of cytokinesis protein 8 | Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:22461490, PubMed:28028151). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (By similarity). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing (PubMed:25762780). {ECO:0000250|UniProtKB:Q8C147, ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:25762780, ECO:0000269|PubMed:28028151}. |
| Q8NFC6 | BOD1L1 | S1710 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NFH5 | NUP35 | S105 | ochoa | Nucleoporin NUP35 (35 kDa nucleoporin) (Mitotic phosphoprotein 44) (MP-44) (Nuclear pore complex protein Nup53) (Nucleoporin NUP53) | Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. May play a role in the association of MAD1 with the NPC. {ECO:0000269|PubMed:15703211}. |
| Q8NFH5 | NUP35 | S279 | ochoa | Nucleoporin NUP35 (35 kDa nucleoporin) (Mitotic phosphoprotein 44) (MP-44) (Nuclear pore complex protein Nup53) (Nucleoporin NUP53) | Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. May play a role in the association of MAD1 with the NPC. {ECO:0000269|PubMed:15703211}. |
| Q8NFH8 | REPS2 | S239 | ochoa | RalBP1-associated Eps domain-containing protein 2 (Partner of RalBP1) (RalBP1-interacting protein 2) | Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors as part of the Ral signaling pathway (PubMed:10393179, PubMed:12771942, PubMed:9422736). By controlling growth factor receptors endocytosis may regulate cell survival (PubMed:12771942). Through ASAP1 may regulate cell adhesion and migration (PubMed:12149250). {ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:12149250, ECO:0000269|PubMed:12771942, ECO:0000269|PubMed:9422736}. |
| Q8NFZ4 | NLGN2 | S720 | ochoa | Neuroligin-2 | Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Promotes clustering of postsynaptic LHFPL4 (By similarity). Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q69ZK9}. |
| Q8NHW3 | MAFA | S49 | psp | Transcription factor MafA (Pancreatic beta-cell-specific transcriptional activator) (RIPE3b1 factor) (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) | Transcription factor that activates insulin gene expression (PubMed:12011435, PubMed:15993959). Acts synergistically with NEUROD1/BETA2 and PDX1 (PubMed:15993959). Binds the insulin enhancer C1/RIPE3b element (PubMed:12011435). Binds to consensus TRE-type MARE 5'-TGCTGACTCAGCA-3' DNA sequence (PubMed:23148532, PubMed:29339498). {ECO:0000269|PubMed:12011435, ECO:0000269|PubMed:15993959, ECO:0000269|PubMed:23148532, ECO:0000269|PubMed:29339498}. |
| Q8NHY2 | COP1 | S108 | ochoa | E3 ubiquitin-protein ligase COP1 (EC 2.3.2.27) (Constitutive photomorphogenesis protein 1 homolog) (hCOP1) (RING finger and WD repeat domain protein 2) (RING finger protein 200) (RING-type E3 ubiquitin transferase RFWD2) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif (Probable). {ECO:0000269|PubMed:12466024, ECO:0000269|PubMed:12615916, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15103385, ECO:0000269|PubMed:19805145, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21625211, ECO:0000303|PubMed:27041596}. |
| Q8NI35 | PATJ | S1618 | ochoa | InaD-like protein (Inadl protein) (hINADL) (Channel-interacting PDZ domain-containing protein) (Pals1-associated tight junction protein) (Protein associated to tight junctions) | Scaffolding protein that facilitates the localization of proteins to the cell membrane (PubMed:11927608, PubMed:16678097, PubMed:22006950). Required for the correct formation of tight junctions and epithelial apico-basal polarity (PubMed:11927608, PubMed:16678097). Acts (via its L27 domain) as an apical connector and elongation factor for multistranded TJP1/ZO1 condensates that form a tight junction belt, thereby required for the formation of the tight junction-mediated cell barrier (By similarity). Positively regulates epithelial cell microtubule elongation and cell migration, possibly via facilitating localization of PRKCI/aPKC and PAR3D/PAR3 at the leading edge of migrating cells (By similarity). Plays a role in the correct reorientation of the microtubule-organizing center during epithelial migration (By similarity). May regulate the surface expression and/or function of ASIC3 in sensory neurons (By similarity). May recruit ARHGEF18 to apical cell-cell boundaries (PubMed:22006950). {ECO:0000250|UniProtKB:E2QYC9, ECO:0000250|UniProtKB:Q63ZW7, ECO:0000269|PubMed:11927608, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:22006950}. |
| Q8TAD8 | SNIP1 | S159 | ochoa | Smad nuclear-interacting protein 1 (FHA domain-containing protein SNIP1) | Required for pre-mRNA splicing as component of the spliceosome (PubMed:29360106). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:11567019, ECO:0000269|PubMed:15378006, ECO:0000269|PubMed:18632581, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:29360106, ECO:0000305|PubMed:33509932}. |
| Q8TBB1 | LNX1 | S238 | ochoa | E3 ubiquitin-protein ligase LNX (EC 2.3.2.27) (Ligand of Numb-protein X 1) (Numb-binding protein 1) (PDZ domain-containing RING finger protein 2) (RING-type E3 ubiquitin transferase LNX) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65. {ECO:0000250|UniProtKB:O70263}.; FUNCTION: Isoform 2 provides an endocytic scaffold for IGSF5/JAM4. {ECO:0000250|UniProtKB:O70263}. |
| Q8TBE0 | BAHD1 | S545 | ochoa | Bromo adjacent homology domain-containing 1 protein (BAH domain-containing protein 1) | Heterochromatin protein that acts as a transcription repressor and has the ability to promote the formation of large heterochromatic domains. May act by recruiting heterochromatin proteins such as CBX5 (HP1 alpha), HDAC5 and MBD1. Represses IGF2 expression by binding to its CpG-rich P3 promoter and recruiting heterochromatin proteins. At specific stages of Listeria infection, in complex with TRIM28, corepresses interferon-stimulated genes, including IFNL1, IFNL2 and IFNL3. {ECO:0000269|PubMed:19666599, ECO:0000269|PubMed:21252314}. |
| Q8TBM8 | DNAJB14 | S69 | ochoa | DnaJ homolog subfamily B member 14 | Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway (PubMed:24732912). Acts by determining HSPA8/Hsc70's ATPase and polypeptide-binding activities (PubMed:24732912). Can also act independently of HSPA8/Hsc70: together with DNAJB12, acts as a chaperone that promotes maturation of potassium channels KCND2 and KCNH2 by stabilizing nascent channel subunits and assembling them into tetramers (PubMed:27916661). While stabilization of nascent channel proteins is dependent on HSPA8/Hsc70, the process of oligomerization of channel subunits is independent of HSPA8/Hsc70 (PubMed:27916661). When overexpressed, forms membranous structures together with DNAJB12 and HSPA8/Hsc70 within the nucleus; the role of these structures, named DJANGOs, is still unclear (PubMed:24732912). {ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27916661}.; FUNCTION: (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection (PubMed:21673190, PubMed:24675744). {ECO:0000269|PubMed:21673190, ECO:0000269|PubMed:24675744}. |
| Q8TBZ3 | WDR20 | S445 | ochoa | WD repeat-containing protein 20 (Protein DMR) | Regulator of deubiquitinating complexes. Activates deubiquitinating activity of complexes containing USP12 (PubMed:20147737, PubMed:27373336). Anchors at the base of the ubiquitin-contacting loop of USP12 and remotely modulates the catalytic center of the enzyme (PubMed:27373336). Regulates shuttling of the USP12 deubiquitinase complex between the plasma membrane, cytoplasm and nucleus (PubMed:30466959). {ECO:0000269|PubMed:20147737, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:30466959}. |
| Q8TC90 | CCER1 | S240 | ochoa | Coiled-coil domain-containing glutamate-rich protein 1 | Regulator of histone epigenetic modifications and chromatin compaction into the sperm head, required for histone-to-protamine (HTP) transition. HTP is a key event in which somatic histones are first replaced by testis-specific histone variants, then transition proteins (TNPs) are incorporated into the spermatid nucleus, and finally protamines (PRMs) replace the TNPs to promote chromatin condensation. {ECO:0000250|UniProtKB:Q9CQL2}. |
| Q8TCG5 | CPT1C | S775 | ochoa | Palmitoyl thioesterase CPT1C (EC 3.1.2.22) (Carnitine O-palmitoyltransferase 1, brain isoform) (CPTI-B) (Carnitine palmitoyltransferase 1C) (Carnitine palmitoyltransferase I) (CPT I-C) | Palmitoyl thioesterase specifically expressed in the endoplasmic reticulum of neurons. Modulates the trafficking of the glutamate receptor, AMPAR, to plasma membrane through depalmitoylation of GRIA1 (PubMed:30135643). Also regulates AMPR trafficking through the regulation of SACM1L phosphatidylinositol-3-phosphatase activity by interaction in a malonyl-CoA dependent manner (By similarity). Binds malonyl-CoA and couples malonyl-CoA to ceramide levels, necessary for proper spine maturation and contributing to systemic energy homeostasis and appetite control (PubMed:16651524). Binds to palmitoyl-CoA, but does not have carnitine palmitoyltransferase 1 catalytic activity or at very low levels (PubMed:25751282, PubMed:30135643). {ECO:0000250|UniProtKB:Q8BGD5, ECO:0000269|PubMed:16651524, ECO:0000269|PubMed:25751282, ECO:0000269|PubMed:30135643}. |
| Q8TD55 | PLEKHO2 | S433 | ochoa | Pleckstrin homology domain-containing family O member 2 (PH domain-containing family O member 2) (Pleckstrin homology domain-containing family Q member 1) (PH domain-containing family Q member 1) | None |
| Q8TDJ6 | DMXL2 | S473 | ochoa | DmX-like protein 2 (Rabconnectin-3) | May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles (PubMed:11809763). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (By similarity). {ECO:0000250|UniProtKB:Q8BPN8, ECO:0000269|PubMed:11809763}. |
| Q8TDM6 | DLG5 | S864 | ochoa | Disks large homolog 5 (Discs large protein P-dlg) (Placenta and prostate DLG) | Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling pathway by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial-mesenchymal transition (EMT), cell migration and invasion (PubMed:28169360). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N-cadherin. Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:E9Q9R9, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360}. |
| Q8TDM6 | DLG5 | S941 | ochoa | Disks large homolog 5 (Discs large protein P-dlg) (Placenta and prostate DLG) | Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling pathway by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial-mesenchymal transition (EMT), cell migration and invasion (PubMed:28169360). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N-cadherin. Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:E9Q9R9, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360}. |
| Q8TDM6 | DLG5 | S1252 | ochoa | Disks large homolog 5 (Discs large protein P-dlg) (Placenta and prostate DLG) | Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling pathway by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial-mesenchymal transition (EMT), cell migration and invasion (PubMed:28169360). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N-cadherin. Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:E9Q9R9, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360}. |
| Q8TDN6 | BRIX1 | S247 | ochoa | Ribosome biogenesis protein BRX1 homolog (Brix domain-containing protein 2) | Required for biogenesis of the 60S ribosomal subunit. |
| Q8TER5 | ARHGEF40 | S1490 | ochoa | Rho guanine nucleotide exchange factor 40 (Protein SOLO) | May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}. |
| Q8TEV9 | SMCR8 | S417 | ochoa | Guanine nucleotide exchange protein SMCR8 (Smith-Magenis syndrome chromosomal region candidate gene 8 protein) | Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27103069, PubMed:27193190, PubMed:27559131, PubMed:27617292, PubMed:28195531, PubMed:32303654). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (PubMed:32303654). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531). {ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27559131, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531, ECO:0000269|PubMed:32303654}. |
| Q8TF40 | FNIP1 | S686 | ochoa | Folliculin-interacting protein 1 | Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491, PubMed:37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:37079666). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development (PubMed:32905580). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:32905580, ECO:0000269|PubMed:37079666}. |
| Q8TF44 | C2CD4C | S178 | ochoa | C2 calcium-dependent domain-containing protein 4C (Nuclear-localized factor 3) (Protein FAM148C) | None |
| Q8TF71 | SLC16A10 | S266 | ochoa | Monocarboxylate transporter 10 (MCT 10) (Aromatic amino acid transporter 1) (Solute carrier family 16 member 10) (T-type amino acid transporter 1) | Sodium- and proton-independent thyroid hormones and aromatic acids transporter (PubMed:11827462, PubMed:18337592, PubMed:28754537). Mediates both uptake and efflux of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) with high affinity, suggesting a role in the homeostasis of thyroid hormone levels (PubMed:18337592). Responsible for low affinity bidirectional transport of the aromatic amino acids, such as phenylalanine, tyrosine, tryptophan and L-3,4-dihydroxyphenylalanine (L-dopa) (PubMed:11827462, PubMed:28754537). Plays an important role in homeostasis of aromatic amino acids (By similarity). {ECO:0000250|UniProtKB:Q3U9N9, ECO:0000269|PubMed:11827462, ECO:0000269|PubMed:18337592, ECO:0000269|PubMed:28754537}. |
| Q8TF71 | SLC16A10 | S268 | ochoa | Monocarboxylate transporter 10 (MCT 10) (Aromatic amino acid transporter 1) (Solute carrier family 16 member 10) (T-type amino acid transporter 1) | Sodium- and proton-independent thyroid hormones and aromatic acids transporter (PubMed:11827462, PubMed:18337592, PubMed:28754537). Mediates both uptake and efflux of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) with high affinity, suggesting a role in the homeostasis of thyroid hormone levels (PubMed:18337592). Responsible for low affinity bidirectional transport of the aromatic amino acids, such as phenylalanine, tyrosine, tryptophan and L-3,4-dihydroxyphenylalanine (L-dopa) (PubMed:11827462, PubMed:28754537). Plays an important role in homeostasis of aromatic amino acids (By similarity). {ECO:0000250|UniProtKB:Q3U9N9, ECO:0000269|PubMed:11827462, ECO:0000269|PubMed:18337592, ECO:0000269|PubMed:28754537}. |
| Q8TF72 | SHROOM3 | S1131 | ochoa | Protein Shroom3 (Shroom-related protein) (hShrmL) | Controls cell shape changes in the neuroepithelium during neural tube closure. Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers (By similarity). Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays (By similarity). {ECO:0000250|UniProtKB:Q27IV2, ECO:0000250|UniProtKB:Q9QXN0}. |
| Q8TF74 | WIPF2 | S70 | ochoa | WAS/WASL-interacting protein family member 2 (WASP-interacting protein-related protein) (WIP- and CR16-homologous protein) (WIP-related protein) | Plays an active role in the formation of cell surface protrusions downstream of activated PDGFB receptors. Plays an important role in actin-microspike formation through cooperation with WASL. May cooperate with WASP and WASL to induce mobilization and reorganization of the actin filament system. {ECO:0000269|PubMed:11829459, ECO:0000269|PubMed:12213210}. |
| Q8TF74 | WIPF2 | S76 | ochoa | WAS/WASL-interacting protein family member 2 (WASP-interacting protein-related protein) (WIP- and CR16-homologous protein) (WIP-related protein) | Plays an active role in the formation of cell surface protrusions downstream of activated PDGFB receptors. Plays an important role in actin-microspike formation through cooperation with WASL. May cooperate with WASP and WASL to induce mobilization and reorganization of the actin filament system. {ECO:0000269|PubMed:11829459, ECO:0000269|PubMed:12213210}. |
| Q8WU79 | SMAP2 | S231 | ochoa | Stromal membrane-associated protein 2 (Stromal membrane-associated protein 1-like) | GTPase activating protein that acts on ARF1. Can also activate ARF6 (in vitro). May play a role in clathrin-dependent retrograde transport from early endosomes to the trans-Golgi network (By similarity). {ECO:0000250}. |
| Q8WUF5 | PPP1R13L | S151 | ochoa | RelA-associated inhibitor (Inhibitor of ASPP protein) (Protein iASPP) (NFkB-interacting protein 1) (PPP1R13B-like protein) | Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (PubMed:12524540). Is involved in NF-kappa-B dependent negative regulation of inflammatory response (PubMed:28069640). {ECO:0000269|PubMed:10336463, ECO:0000269|PubMed:12134007, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:15489900, ECO:0000269|PubMed:28069640}. |
| Q8WUF5 | PPP1R13L | S335 | ochoa | RelA-associated inhibitor (Inhibitor of ASPP protein) (Protein iASPP) (NFkB-interacting protein 1) (PPP1R13B-like protein) | Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (PubMed:12524540). Is involved in NF-kappa-B dependent negative regulation of inflammatory response (PubMed:28069640). {ECO:0000269|PubMed:10336463, ECO:0000269|PubMed:12134007, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:15489900, ECO:0000269|PubMed:28069640}. |
| Q8WUJ0 | STYX | S201 | ochoa | Serine/threonine/tyrosine-interacting protein (Inactive tyrosine-protein phosphatase STYX) (Phosphoserine/threonine/tyrosine interaction protein) | Catalytically inactive phosphatase (PubMed:23847209). Acts as a nuclear anchor for MAPK1/MAPK3 (ERK1/ERK2) (PubMed:23847209). Modulates cell-fate decisions and cell migration by spatiotemporal regulation of MAPK1/MAPK3 (ERK1/ERK2) (PubMed:23847209). By binding to the F-box of FBXW7, prevents the assembly of FBXW7 into the SCF E3 ubiquitin-protein ligase complex, and thereby inhibits degradation of its substrates (PubMed:28007894). Plays a role in spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q60969, ECO:0000269|PubMed:23847209, ECO:0000269|PubMed:28007894}. |
| Q8WUM0 | NUP133 | S27 | ochoa | Nuclear pore complex protein Nup133 (133 kDa nucleoporin) (Nucleoporin Nup133) | Involved in poly(A)+ RNA transport. Involved in nephrogenesis (PubMed:30179222). {ECO:0000269|PubMed:11684705, ECO:0000269|PubMed:30179222}. |
| Q8WW12 | PCNP | S77 | ochoa | PEST proteolytic signal-containing nuclear protein (PCNP) (PEST-containing nuclear protein) | May be involved in cell cycle regulation. |
| Q8WWM7 | ATXN2L | S396 | ochoa | Ataxin-2-like protein (Ataxin-2 domain protein) (Ataxin-2-related protein) | Involved in the regulation of stress granule and P-body formation. {ECO:0000269|PubMed:23209657}. |
| Q8WWQ0 | PHIP | S1762 | ochoa | PH-interacting protein (PHIP) (DDB1- and CUL4-associated factor 14) (IRS-1 PH domain-binding protein) (WD repeat-containing protein 11) | Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}. |
| Q8WXE0 | CASKIN2 | S409 | ochoa | Caskin-2 (CASK-interacting protein 2) | None |
| Q8WXF1 | PSPC1 | S481 | ochoa | Paraspeckle component 1 (Paraspeckle protein 1) | RNA-binding protein required for the formation of nuclear paraspeckles (PubMed:22416126). Binds to poly(A), poly(G) and poly(U) RNA homopolymers (PubMed:22416126). Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000250|UniProtKB:Q8R326, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:28712728}. |
| Q8WXS5 | CACNG8 | S252 | ochoa | Voltage-dependent calcium channel gamma-8 subunit (Neuronal voltage-gated calcium channel gamma-8 subunit) (Transmembrane AMPAR regulatory protein gamma-8) (TARP gamma-8) | Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. {ECO:0000250|UniProtKB:Q8VHW2, ECO:0000269|PubMed:20805473, ECO:0000269|PubMed:21172611}. |
| Q8WZ75 | ROBO4 | S663 | ochoa | Roundabout homolog 4 (Magic roundabout) | Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins (By similarity). Involved in the maintenance of endothelial barrier organization and function (PubMed:30455415). {ECO:0000250, ECO:0000269|PubMed:30455415}. |
| Q92538 | GBF1 | S325 | ochoa | Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (BFA-resistant GEF 1) | Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER) (PubMed:12047556, PubMed:12808027, PubMed:16926190, PubMed:17956946, PubMed:18003980, PubMed:19039328, PubMed:24213530). Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adaptor protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5) (PubMed:23386609). Has GEF activity towards ARF1 (PubMed:15616190). Has in vitro GEF activity towards ARF5 (By similarity). Involved in the processing of PSAP (PubMed:17666033). Required for the assembly of the Golgi apparatus (PubMed:12808027, PubMed:18003980). The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions (PubMed:18063581, PubMed:23418352). May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate (PubMed:19461073, PubMed:22185782). In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex (PubMed:22573891). Plays a role in maintaining mitochondrial morphology (PubMed:25190516). {ECO:0000250|UniProtKB:Q9R1D7, ECO:0000269|PubMed:12047556, ECO:0000269|PubMed:12808027, ECO:0000269|PubMed:15616190, ECO:0000269|PubMed:16926190, ECO:0000269|PubMed:17666033, ECO:0000269|PubMed:17956946, ECO:0000269|PubMed:18003980, ECO:0000269|PubMed:18063581, ECO:0000269|PubMed:19461073, ECO:0000269|PubMed:22185782, ECO:0000269|PubMed:22573891, ECO:0000269|PubMed:23386609, ECO:0000269|PubMed:23418352, ECO:0000269|PubMed:24213530, ECO:0000269|PubMed:25190516, ECO:0000305|PubMed:19039328, ECO:0000305|PubMed:22573891}. |
| Q92574 | TSC1 | S515 | ochoa | Hamartin (Tuberous sclerosis 1 protein) | Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155). {ECO:0000250|UniProtKB:Q9Z136, ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:16464865, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:33215753, ECO:0000269|PubMed:9242607}. |
| Q92575 | UBXN4 | S330 | ochoa | UBX domain-containing protein 4 (Erasin) (UBX domain-containing protein 2) | Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD (PubMed:19822669). {ECO:0000269|PubMed:16968747, ECO:0000269|PubMed:19822669}. |
| Q92585 | MAML1 | S286 | ochoa | Mastermind-like protein 1 (Mam-1) | Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}. |
| Q92585 | MAML1 | S321 | ochoa | Mastermind-like protein 1 (Mam-1) | Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}. |
| Q92609 | TBC1D5 | S725 | ochoa | TBC1 domain family member 5 | May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity (PubMed:19531583, PubMed:20923837). Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy (PubMed:22354992). May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (PubMed:24603492). {ECO:0000269|PubMed:19531583, ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22354992, ECO:0000269|PubMed:24603492, ECO:0000305|PubMed:19531583, ECO:0000305|PubMed:22354992, ECO:0000305|PubMed:24603492}. |
| Q92613 | JADE3 | S672 | ochoa | Protein Jade-3 (Jade family PHD finger protein 3) (PHD finger protein 16) | Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. {ECO:0000269|PubMed:16387653}. |
| Q92614 | MYO18A | S112 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92614 | MYO18A | S116 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92619 | ARHGAP45 | S53 | ochoa | Rho GTPase-activating protein 45 [Cleaved into: Minor histocompatibility antigen HA-1 (mHag HA-1)] | Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity. {ECO:0000269|PubMed:24086303}.; FUNCTION: Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL. {ECO:0000269|PubMed:12601144, ECO:0000269|PubMed:8260714, ECO:0000269|PubMed:8532022, ECO:0000269|PubMed:9798702}. |
| Q92619 | ARHGAP45 | S878 | ochoa | Rho GTPase-activating protein 45 [Cleaved into: Minor histocompatibility antigen HA-1 (mHag HA-1)] | Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity. {ECO:0000269|PubMed:24086303}.; FUNCTION: Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL. {ECO:0000269|PubMed:12601144, ECO:0000269|PubMed:8260714, ECO:0000269|PubMed:8532022, ECO:0000269|PubMed:9798702}. |
| Q92667 | AKAP1 | S573 | ochoa | A-kinase anchor protein 1, mitochondrial (A-kinase anchor protein 149 kDa) (AKAP 149) (Dual specificity A-kinase-anchoring protein 1) (D-AKAP-1) (Protein kinase A-anchoring protein 1) (PRKA1) (Spermatid A-kinase anchor protein 84) (S-AKAP84) | Binds to type I and II regulatory subunits of protein kinase A and anchors them to the cytoplasmic face of the mitochondrial outer membrane (By similarity). Involved in mitochondrial-mediated antiviral innate immunity (PubMed:31522117). Promotes translocation of NDUFS1 into mitochondria to regulate mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) activity (By similarity). {ECO:0000250|UniProtKB:O08715, ECO:0000269|PubMed:31522117}. |
| Q92783 | STAM | S147 | ochoa | Signal transducing adapter molecule 1 (STAM-1) | Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.; FUNCTION: (Microbial infection) Plays an important role in Dengue virus entry. {ECO:0000269|PubMed:29742433}. |
| Q92793 | CREBBP | S78 | psp | CREB-binding protein (Histone lysine acetyltransferase CREBBP) (EC 2.3.1.48) (Protein lactyltransferas CREBBP) (EC 2.3.1.-) (Protein-lysine acetyltransferase CREBBP) (EC 2.3.1.-) | Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:35675826, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9707565}. |
| Q92793 | CREBBP | S1578 | ochoa | CREB-binding protein (Histone lysine acetyltransferase CREBBP) (EC 2.3.1.48) (Protein lactyltransferas CREBBP) (EC 2.3.1.-) (Protein-lysine acetyltransferase CREBBP) (EC 2.3.1.-) | Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:35675826, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9707565}. |
| Q92796 | DLG3 | S493 | ochoa | Disks large homolog 3 (Neuroendocrine-DLG) (Synapse-associated protein 102) (SAP-102) (SAP102) (XLMR) | Required for learning most likely through its role in synaptic plasticity following NMDA receptor signaling. |
| Q92817 | EVPL | S1794 | ochoa | Envoplakin (210 kDa cornified envelope precursor protein) (210 kDa paraneoplastic pemphigus antigen) (p210) | Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. |
| Q92854 | SEMA4D | S798 | ochoa | Semaphorin-4D (A8) (BB18) (GR3) (CD antigen CD100) | Cell surface receptor for PLXNB1 and PLXNB2 that plays an important role in cell-cell signaling (PubMed:20877282). Regulates GABAergic synapse development (By similarity). Promotes the development of inhibitory synapses in a PLXNB1-dependent manner (By similarity). Modulates the complexity and arborization of developing neurites in hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 mediates activation of RHOA (PubMed:19788569). Promotes the migration of cerebellar granule cells (PubMed:16055703). Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro) (PubMed:8876214). Induces endothelial cell migration through the activation of PTK2B/PYK2, SRC, and the phosphatidylinositol 3-kinase-AKT pathway (PubMed:16055703). {ECO:0000250|UniProtKB:O09126, ECO:0000269|PubMed:16055703, ECO:0000269|PubMed:19788569, ECO:0000269|PubMed:20877282, ECO:0000269|PubMed:8876214}. |
| Q92878 | RAD50 | S635 | ochoa|psp | DNA repair protein RAD50 (hRAD50) (EC 3.6.-.-) | Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28134932, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:15064416, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:11741547, PubMed:9590181, PubMed:9651580, PubMed:9705271). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:11741547, PubMed:12805565, PubMed:28134932). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q9X1X1, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:12805565, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28134932, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}. |
| Q92890 | UFD1 | S231 | ochoa | Ubiquitin recognition factor in ER-associated degradation protein 1 (Ubiquitin fusion degradation protein 1) (UB fusion protein 1) | Essential component of the ubiquitin-dependent proteolytic pathway which degrades ubiquitin fusion proteins. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. It may be involved in the development of some ectoderm-derived structures (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and NPLOC4, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (PubMed:26471729). {ECO:0000250|UniProtKB:Q9ES53, ECO:0000269|PubMed:26471729}. |
| Q92934 | BAD | S34 | ochoa | Bcl2-associated agonist of cell death (BAD) (Bcl-2-binding component 6) (Bcl-2-like protein 8) (Bcl2-L-8) (Bcl-xL/Bcl-2-associated death promoter) (Bcl2 antagonist of cell death) | Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways. {ECO:0000250}. |
| Q92945 | KHSRP | S319 | ochoa | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q92945 | KHSRP | S670 | ochoa|psp | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q92953 | KCNB2 | S448 | ochoa | Potassium voltage-gated channel subfamily B member 2 (Voltage-gated potassium channel subunit Kv2.2) | Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells. {ECO:0000250|UniProtKB:A6H8H5, ECO:0000250|UniProtKB:Q63099}. |
| Q92974 | ARHGEF2 | S137 | ochoa | Rho guanine nucleotide exchange factor 2 (Guanine nucleotide exchange factor H1) (GEF-H1) (Microtubule-regulated Rho-GEF) (Proliferating cell nucleolar antigen p40) | Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (By similarity). Involved in neuronal progenitor cell division and differentiation (PubMed:28453519). Involved in the migration of precerebellar neurons (By similarity). {ECO:0000250|UniProtKB:Q60875, ECO:0000250|UniProtKB:Q865S3, ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:28453519, ECO:0000269|PubMed:9857026}. |
| Q92997 | DVL3 | S280 | psp | Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) | Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}. |
| Q92997 | DVL3 | S603 | psp | Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) | Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}. |
| Q93074 | MED12 | S557 | ochoa | Mediator of RNA polymerase II transcription subunit 12 (Activator-recruited cofactor 240 kDa component) (ARC240) (CAG repeat protein 45) (Mediator complex subunit 12) (OPA-containing protein) (Thyroid hormone receptor-associated protein complex 230 kDa component) (Trap230) (Trinucleotide repeat-containing gene 11 protein) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway. {ECO:0000269|PubMed:16565090, ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:17000779}. |
| Q93074 | MED12 | S1258 | ochoa | Mediator of RNA polymerase II transcription subunit 12 (Activator-recruited cofactor 240 kDa component) (ARC240) (CAG repeat protein 45) (Mediator complex subunit 12) (OPA-containing protein) (Thyroid hormone receptor-associated protein complex 230 kDa component) (Trap230) (Trinucleotide repeat-containing gene 11 protein) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway. {ECO:0000269|PubMed:16565090, ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:17000779}. |
| Q969H0 | FBXW7 | S18 | psp | F-box/WD repeat-containing protein 7 (Archipelago homolog) (hAgo) (F-box and WD-40 domain-containing protein 7) (F-box protein FBX30) (SEL-10) (hCdc4) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:17434132, PubMed:22748924, PubMed:26976582, PubMed:28727686, PubMed:34741373, PubMed:35395208). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:17434132, PubMed:22748924, PubMed:26774286, PubMed:26976582, PubMed:28727686, PubMed:34741373). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and probably PSEN1 (PubMed:11565034, PubMed:11585921, PubMed:12354302, PubMed:14739463, PubMed:15103331, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:25775507, PubMed:25897075, PubMed:26976582, PubMed:28007894, PubMed:28727686, PubMed:29149593, PubMed:34102342). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (PubMed:26774286). {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:26976582, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:28007894, ECO:0000269|PubMed:28727686, ECO:0000269|PubMed:29149593, ECO:0000269|PubMed:34102342, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:35395208, ECO:0000305|PubMed:12354302}. |
| Q969V6 | MRTFA | S449 | ochoa | Myocardin-related transcription factor A (MRTF-A) (MKL/myocardin-like protein 1) (Megakaryoblastic leukemia 1 protein) (Megakaryocytic acute leukemia protein) | Transcription coactivator that associates with the serum response factor (SRF) transcription factor to control expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration (PubMed:26224645). The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. MRTFA binds G-actin via its RPEL repeats, regulating activity of the MRTFA-SRF complex. Activity is also regulated by filamentous actin (F-actin) in the nucleus. {ECO:0000250|UniProtKB:Q8K4J6, ECO:0000269|PubMed:26224645}. |
| Q96A22 | C11orf52 | S62 | ochoa | Uncharacterized protein C11orf52 | None |
| Q96B97 | SH3KBP1 | S444 | ochoa | SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) | Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}. |
| Q96BV0 | ZNF775 | S71 | ochoa | Zinc finger protein 775 | May be involved in transcriptional regulation. |
| Q96BY6 | DOCK10 | S1410 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96C24 | SYTL4 | S289 | ochoa | Synaptotagmin-like protein 4 (Exophilin-2) (Granuphilin) | Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner (By similarity). {ECO:0000250}. |
| Q96CP6 | GRAMD1A | S271 | ochoa | Protein Aster-A (GRAM domain-containing protein 1A) | Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). May play a role in tumor progression (By similarity). Plays a role in autophagy regulation and is required for biogenesis of the autophagosome (PubMed:31222192). This function in autophagy requires its cholesterol-transfer activity (PubMed:31222192). {ECO:0000250|UniProtKB:Q8VEF1, ECO:0000269|PubMed:31222192}. |
| Q96CT7 | CCDC124 | S141 | ochoa | Coiled-coil domain-containing protein 124 | Ribosome-binding protein involved in ribosome hibernation: associates with translationally inactive ribosomes and stabilizes the nonrotated conformation of the 80S ribosome, thereby promoting ribosome preservation and storage (PubMed:32687489). Also required for proper progression of late cytokinetic stages (PubMed:23894443). {ECO:0000269|PubMed:23894443, ECO:0000269|PubMed:32687489}. |
| Q96CV9 | OPTN | S191 | ochoa | Optineurin (E3-14.7K-interacting protein) (FIP-2) (Huntingtin yeast partner L) (Huntingtin-interacting protein 7) (HIP-7) (Huntingtin-interacting protein L) (NEMO-related protein) (Optic neuropathy-inducing protein) (Transcription factor IIIA-interacting protein) (TFIIIA-IntP) | Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8 (PubMed:27534431). Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation (PubMed:27534431). Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation (PubMed:27538435). In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and huntingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment (PubMed:22854040). Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:27534431, ECO:0000269|PubMed:27538435}.; FUNCTION: (Microbial infection) May constitute a cellular target for various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to inhibit innate immune response (PubMed:27538435, PubMed:9488477). During RNA virus infection, such as that of Sendai virus, negatively regulates the induction of IFNB1 (PubMed:20174559). {ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:27538435, ECO:0000269|PubMed:9488477}. |
| Q96D05 | FAM241B | S28 | ochoa | Protein FAM241B | May play a role in lysosome homeostasis. {ECO:0000269|PubMed:31270356}. |
| Q96D71 | REPS1 | S125 | ochoa | RalBP1-associated Eps domain-containing protein 1 (RalBP1-interacting protein 1) | May coordinate the cellular actions of activated EGF receptors and Ral-GTPases. {ECO:0000250}. |
| Q96DT7 | ZBTB10 | S565 | ochoa | Zinc finger and BTB domain-containing protein 10 (Zinc finger protein RIN ZF) | May be involved in transcriptional regulation. |
| Q96EI5 | TCEAL4 | S108 | ochoa | Transcription elongation factor A protein-like 4 (TCEA-like protein 4) (Transcription elongation factor S-II protein-like 4) | May be involved in transcriptional regulation. |
| Q96EK9 | KTI12 | S200 | ochoa | Protein KTI12 homolog | None |
| Q96F46 | IL17RA | S730 | ochoa | Interleukin-17 receptor A (IL-17 receptor A) (IL-17RA) (CDw217) (CD antigen CD217) | Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911633, PubMed:9367539). Receptor for IL17F (PubMed:17911633, PubMed:19838198). Binds to IL17A with higher affinity than to IL17F (PubMed:17911633). Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (PubMed:16785495). Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (PubMed:18684971). Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16785495, PubMed:17911633, PubMed:18684971, PubMed:21350122, PubMed:24120361). Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (By similarity). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity). Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (By similarity). Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848). {ECO:0000250|UniProtKB:Q60943, ECO:0000269|PubMed:16785495, ECO:0000269|PubMed:17911633, ECO:0000269|PubMed:18684971, ECO:0000269|PubMed:19838198, ECO:0000269|PubMed:21350122, ECO:0000269|PubMed:21993848, ECO:0000269|PubMed:24120361, ECO:0000269|PubMed:9367539}.; FUNCTION: (Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway. {ECO:0000269|PubMed:33723527}. |
| Q96FZ2 | HMCES | S154 | ochoa | Abasic site processing protein HMCES (EC 4.-.-.-) (Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein) (ES cell-specific 5hmC-binding protein) (Peptidase HMCES) (EC 3.4.-.-) (SRAP domain-containing protein 1) | Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites (PubMed:30554877, PubMed:31235913, PubMed:31235915, PubMed:32307824, PubMed:32492421). Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue (PubMed:30554877, PubMed:31235913). Promotes error-free repair by protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks (PubMed:30554877). The HMCES DNA-protein cross-link is then either reversed or degraded (PubMed:30554877, PubMed:36608669, PubMed:37519246, PubMed:37950866). HMCES is able to catalyze the reversal of its thiazolidine cross-link and cycle between a cross-link and a non-cross-linked state depending on DNA context: mediates self-reversal of the thiazolidine cross-link in double stranded DNA, allowing APEX1 to initiate downstream repair of abasic sites (PubMed:37519246, PubMed:37950866). The HMCES DNA-protein cross-link can also be degraded by the SPRTN metalloprotease following unfolding by the BRIP1/FANCJ helicase (PubMed:36608669). Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (PubMed:31235915, PubMed:31806351). Plays a protective role during somatic hypermutation of immunoglobulin genes in B-cells: acts via its ability to form covalent cross-links with abasic sites, thereby limiting the accumulation of deletions in somatic hypermutation target regions (PubMed:35450882). Also involved in class switch recombination (CSR) in B-cells independently of the formation of a DNA-protein cross-link: acts by binding and protecting ssDNA overhangs to promote DNA double-strand break repair through the microhomology-mediated alternative-end-joining (Alt-EJ) pathway (By similarity). Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity). {ECO:0000250|UniProtKB:Q8R1M0, ECO:0000269|PubMed:30554877, ECO:0000269|PubMed:31235913, ECO:0000269|PubMed:31235915, ECO:0000269|PubMed:31806351, ECO:0000269|PubMed:32307824, ECO:0000269|PubMed:32492421, ECO:0000269|PubMed:35450882, ECO:0000269|PubMed:36608669, ECO:0000269|PubMed:37519246, ECO:0000269|PubMed:37950866}. |
| Q96G42 | KLHDC7B | S164 | ochoa | Kelch domain-containing protein 7B | None |
| Q96HA1 | POM121 | S348 | ochoa | Nuclear envelope pore membrane protein POM 121 (Nuclear envelope pore membrane protein POM 121A) (Nucleoporin Nup121) (Pore membrane protein of 121 kDa) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| Q96HC4 | PDLIM5 | S76 | ochoa | PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) | May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}. |
| Q96HC4 | PDLIM5 | S228 | ochoa | PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) | May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}. |
| Q96HH4 | TMEM169 | S20 | ochoa | Transmembrane protein 169 | None |
| Q96HR8 | NAF1 | S34 | ochoa | H/ACA ribonucleoprotein complex non-core subunit NAF1 (hNAF1) | RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex and disappears during maturation of the complex and is replaced by NOLA1/GAR1 to yield mature H/ACA snoRNPs complex. Probably competes with NOLA1/GAR1 for binding with DKC1/NOLA4. {ECO:0000269|PubMed:16618814}. |
| Q96J92 | WNK4 | S1221 | ochoa | Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4) | Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:16832045). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16832045, PubMed:22989884). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (By similarity). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (By similarity). Also inhibits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (By similarity). May also phosphorylate NEDD4L (PubMed:20525693). {ECO:0000250|UniProtKB:Q80UE6, ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:22989884}. |
| Q96JA1 | LRIG1 | S970 | ochoa | Leucine-rich repeats and immunoglobulin-like domains protein 1 (LIG-1) | Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation. {ECO:0000269|PubMed:15282549}. |
| Q96JC9 | EAF1 | S68 | ochoa | ELL-associated factor 1 | Acts as a transcriptional transactivator of ELL and ELL2 elongation activities. {ECO:0000269|PubMed:11418481, ECO:0000269|PubMed:16006523}. |
| Q96JJ3 | ELMO2 | S336 | ochoa | Engulfment and cell motility protein 2 (Protein ced-12 homolog A) (hCed-12A) | Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1. {ECO:0000269|PubMed:11595183, ECO:0000269|PubMed:11703939, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:27476657}. |
| Q96JY6 | PDLIM2 | S178 | ochoa | PDZ and LIM domain protein 2 (PDZ-LIM protein mystique) | Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity. {ECO:0000269|PubMed:15659642}. |
| Q96JY6 | PDLIM2 | S213 | ochoa | PDZ and LIM domain protein 2 (PDZ-LIM protein mystique) | Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity. {ECO:0000269|PubMed:15659642}. |
| Q96K80 | ZC3H10 | S177 | ochoa | Zinc finger CCCH domain-containing protein 10 | Specific regulator of miRNA biogenesis. Binds, via the C3H1-type zinc finger domains, to the binding motif 5'-GCAGCGC-3' on microRNA pri-MIR143 and negatively regulates the processing to mature microRNA. {ECO:0000269|PubMed:28431233}. |
| Q96KQ4 | PPP1R13B | S486 | ochoa | Apoptosis-stimulating of p53 protein 1 (Protein phosphatase 1 regulatory subunit 13B) | Regulator that plays a central role in regulation of apoptosis via its interaction with p53/TP53 (PubMed:11684014, PubMed:12524540). Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. {ECO:0000269|PubMed:11684014, ECO:0000269|PubMed:12524540}. |
| Q96KQ7 | EHMT2 | S242 | ochoa | Histone-lysine N-methyltransferase EHMT2 (EC 2.1.1.-) (EC 2.1.1.367) (Euchromatic histone-lysine N-methyltransferase 2) (HLA-B-associated transcript 8) (Histone H3-K9 methyltransferase 3) (H3-K9-HMTase 3) (Lysine N-methyltransferase 1C) (Protein G9a) | Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000250|UniProtKB:Q9Z148, ECO:0000269|PubMed:11316813, ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:8457211}. |
| Q96KV7 | WDR90 | S349 | ochoa | WD repeat-containing protein 90 | Microtubule-binding protein that plays a crucial role in ensuring inner core protein localization within the centriole core, as well as in maintaining the microtubule wall integrity and the overall centriole roundness and stability (PubMed:32946374). Required for efficient primary cilium formation (PubMed:28781053). {ECO:0000269|PubMed:28781053}. |
| Q96L73 | NSD1 | S961 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-36 specific (EC 2.1.1.357) (Androgen receptor coactivator 267 kDa protein) (Androgen receptor-associated protein of 267 kDa) (H3-K36-HMTase) (Lysine N-methyltransferase 3B) (Nuclear receptor-binding SET domain-containing protein 1) (NR-binding SET domain-containing protein) | Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. |
| Q96LT9 | RNPC3 | S115 | ochoa | RNA-binding region-containing protein 3 (RNA-binding motif protein 40) (RNA-binding protein 40) (U11/U12 small nuclear ribonucleoprotein 65 kDa protein) (U11/U12 snRNP 65 kDa protein) (U11/U12-65K) | Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'-stem-loop of m(7)G-capped U12 snRNA. {ECO:0000269|PubMed:16096647, ECO:0000269|PubMed:19447915, ECO:0000269|PubMed:24480542, ECO:0000269|PubMed:29255062}. |
| Q96MG7 | NSMCE3 | S57 | ochoa | Non-structural maintenance of chromosomes element 3 homolog (Non-SMC element 3 homolog) (Hepatocellular carcinoma-associated protein 4) (MAGE-G1 antigen) (Melanoma-associated antigen G1) (Necdin-like protein 2) | Component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination (PubMed:20864041, PubMed:27427983). The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). In vitro enhances ubiquitin ligase activity of NSMCE1. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex (PubMed:20864041). May be a growth suppressor that facilitates the entry of the cell into cell cycle arrest (By similarity). {ECO:0000250|UniProtKB:Q9CPR8, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:27427983}. |
| Q96MU7 | YTHDC1 | S152 | ochoa | YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) | Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. |
| Q96N67 | DOCK7 | S190 | ochoa | Dedicator of cytokinesis protein 7 | Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}. |
| Q96N67 | DOCK7 | S1438 | ochoa | Dedicator of cytokinesis protein 7 | Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}. |
| Q96NA8 | TSNARE1 | S375 | ochoa | t-SNARE domain-containing protein 1 | None |
| Q96NB3 | ZNF830 | S225 | ochoa | Zinc finger protein 830 (Coiled-coil domain-containing protein 16) | May play a role in pre-mRNA splicing as component of the spliceosome (PubMed:25599396). Acts as an important regulator of the cell cycle that participates in the maintenance of genome integrity. During cell cycle progression in embryonic fibroblast, prevents replication fork collapse, double-strand break formation and cell cycle checkpoint activation. Controls mitotic cell cycle progression and cell survival in rapidly proliferating intestinal epithelium and embryonic stem cells. During the embryo preimplantation, controls different aspects of M phase. During early oocyte growth, plays a role in oocyte survival by preventing chromosomal breaks formation, activation of TP63 and reduction of transcription (By similarity). {ECO:0000250|UniProtKB:Q8R1N0, ECO:0000305|PubMed:25599396}. |
| Q96P48 | ARAP1 | S1419 | ochoa | Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (Centaurin-delta-2) (Cnt-d2) | Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members (PubMed:11804590, PubMed:19666464). Activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding and, to a lesser extent, by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) binding (PubMed:11804590). Has a preference for ARF1 and ARF5 (PubMed:11804590, PubMed:19666464). Positively regulates the ring size of circular dorsal ruffles and promotes macropinocytosis (PubMed:22573888). Acts as a bridging factor in osteoclasts to control actin and membrane dynamics (By similarity). Regulates the condensing of osteoclast podosomes into sealing zones which segregate the bone-facing membrane from other membrane domains and are required for osteoclast resorption activity (By similarity). Also regulates recruitment of the AP-3 complex to endosomal membranes and trafficking of lysosomal membrane proteins to the ruffled membrane border of osteoclasts to modulate bone resorption (By similarity). Regulates the endocytic trafficking of EGFR (PubMed:18764928, PubMed:18939958, PubMed:21275903). Regulates the incorporation of CD63 and CD9 into multivesicular bodies (PubMed:38682696). Required in the retinal pigment epithelium (RPE) for photoreceptor survival due to its role in promoting RPE phagocytosis (By similarity). {ECO:0000250|UniProtKB:Q4LDD4, ECO:0000269|PubMed:11804590, ECO:0000269|PubMed:18764928, ECO:0000269|PubMed:18939958, ECO:0000269|PubMed:19666464, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:22573888, ECO:0000269|PubMed:38682696}. |
| Q96PC5 | MIA2 | S1167 | ochoa | Melanoma inhibitory activity protein 2 (MIA protein 2) (CTAGE family member 5 ER export factor) (Cutaneous T-cell lymphoma-associated antigen 5) (Meningioma-expressed antigen 6/11) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum (PubMed:21525241, PubMed:25202031, PubMed:27138255, PubMed:27170179). Plays a role in the secretion of lipoproteins, pre-chylomicrons and pre-VLDLs, by participating in their export from the endoplasmic reticulum (PubMed:27138255). Thereby, may play a role in cholesterol and triglyceride homeostasis (By similarity). Required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers and recruiting PREB/SEC12 at the endoplasmic reticulum exit sites (PubMed:21525241, PubMed:25202031, PubMed:27170179). {ECO:0000250|UniProtKB:Q91ZV0, ECO:0000269|PubMed:21525241, ECO:0000269|PubMed:25202031, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:27170179}. |
| Q96PE1 | ADGRA2 | S976 | ochoa | Adhesion G protein-coupled receptor A2 (G-protein coupled receptor 124) (Tumor endothelial marker 5) | Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role in Wnt7-specific responses, such as endothelial cell sprouting and migration in the forebrain and neural tube, and establishment of the blood-brain barrier (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling: required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (PubMed:30026314). ADGRA2-tethering function does not rely on its G-protein coupled receptor (GPCR) structure but instead on its combined capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly (PubMed:30026314). Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate (PubMed:16982628). {ECO:0000250|UniProtKB:Q91ZV8, ECO:0000269|PubMed:16982628, ECO:0000269|PubMed:28289266, ECO:0000269|PubMed:30026314}. |
| Q96PE1 | ADGRA2 | S982 | ochoa | Adhesion G protein-coupled receptor A2 (G-protein coupled receptor 124) (Tumor endothelial marker 5) | Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role in Wnt7-specific responses, such as endothelial cell sprouting and migration in the forebrain and neural tube, and establishment of the blood-brain barrier (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling: required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (PubMed:30026314). ADGRA2-tethering function does not rely on its G-protein coupled receptor (GPCR) structure but instead on its combined capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly (PubMed:30026314). Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate (PubMed:16982628). {ECO:0000250|UniProtKB:Q91ZV8, ECO:0000269|PubMed:16982628, ECO:0000269|PubMed:28289266, ECO:0000269|PubMed:30026314}. |
| Q96PE2 | ARHGEF17 | S138 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PE2 | ARHGEF17 | S499 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PK6 | RBM14 | S651 | ochoa | RNA-binding protein 14 (Paraspeckle protein 2) (PSP2) (RNA-binding motif protein 14) (RRM-containing coactivator activator/modulator) (Synaptotagmin-interacting protein) (SYT-interacting protein) | Isoform 1 may function as a nuclear receptor coactivator, enhancing transcription through other coactivators such as NCOA6 and CITED1. Isoform 2, functions as a transcriptional repressor, modulating transcriptional activities of coactivators including isoform 1, NCOA6 and CITED1 (PubMed:11443112). Regulates centriole biogenesis by suppressing the formation of aberrant centriolar protein complexes in the cytoplasm and thus preserving mitotic spindle integrity. Prevents the formation of the STIL-CPAP complex (which can induce the formation of aberrant centriolar protein complexes) by interfering with the interaction of STIL with CPAP (PubMed:25385835). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also involved in the regulation of pre-mRNA alternative splicing (PubMed:37548402). {ECO:0000269|PubMed:11443112, ECO:0000269|PubMed:25385835, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:37548402}. |
| Q96PU8 | QKI | S64 | ochoa | KH domain-containing RNA-binding protein QKI (Protein quaking) (Hqk) (HqkI) | RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and/or translation (PubMed:22398723, PubMed:23630077, PubMed:25768908, PubMed:27029405, PubMed:31331967, PubMed:37379838). Involved in various cellular processes, such as mRNA storage into stress granules, apoptosis, lipid deposition, interferon response, glial cell fate and development (PubMed:25768908, PubMed:31829086, PubMed:34428287, PubMed:37379838). Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence (PubMed:23630077). Acts as a mRNA modification reader that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (PubMed:37379838). Promotes the formation of circular RNAs (circRNAs) during the epithelial to mesenchymal transition and in cardiomyocytes: acts by binding to sites flanking circRNA-forming exons (PubMed:25768908). CircRNAs are produced by back-splicing circularization of pre-mRNAs (PubMed:25768908). Plays a central role in myelinization via 3 distinct mechanisms (PubMed:16641098). First, acts by protecting and promoting stability of target mRNAs such as MBP, SIRT2 and CDKN1B, which promotes oligodendrocyte differentiation (By similarity). Second, participates in mRNA transport by regulating the nuclear export of MBP mRNA (By similarity). Finally, indirectly regulates mRNA splicing of MAG pre-mRNA during oligodendrocyte differentiation by acting as a negative regulator of MAG exon 12 alternative splicing: acts by binding to HNRNPA1 mRNA splicing factor, preventing its translation (By similarity). Involved in microglia differentiation and remyelination by regulating microexon alternative splicing of the Rho GTPase pathway (By similarity). Involved in macrophage differentiation: promotes monocyte differentiation by regulating pre-mRNA splicing in naive peripheral blood monocytes (PubMed:27029405). Acts as an important regulator of muscle development: required for the contractile function of cardiomyocytes by regulating alternative splicing of cardiomyocyte transcripts (By similarity). Acts as a negative regulator of thermogenesis by decreasing stability, nuclear export and translation of mRNAs encoding PPARGC1A and UCP1 (By similarity). Also required for visceral endoderm function and blood vessel development (By similarity). May also play a role in smooth muscle development (PubMed:31331967). In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2 (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:16641098, ECO:0000269|PubMed:22398723, ECO:0000269|PubMed:23630077, ECO:0000269|PubMed:25768908, ECO:0000269|PubMed:27029405, ECO:0000269|PubMed:31331967, ECO:0000269|PubMed:31829086, ECO:0000269|PubMed:34428287, ECO:0000269|PubMed:37379838}.; FUNCTION: [Isoform QKI5]: Nuclear isoform that acts as an indirect regulator of mRNA splicing (By similarity). Regulates mRNA splicing of MAG pre-mRNA by inhibiting translation of HNRNPA1 mRNA, thereby preventing MAG exon 12 alternative splicing (By similarity). Involved in oligodendrocyte differentiation by promoting stabilization of SIRT2 mRNA (By similarity). Acts as a negative regulator of the interferon response by binding to MAVS mRNA, downregulating its expression (PubMed:31829086). Also inhibits the interferon response by binding to fibrinectin FN1 pre-mRNA, repressing EDA exon inclusion in FN1 (PubMed:34428287). Delays macrophage differentiation by binding to CSF1R mRNA, promoting its degradation (PubMed:22398723). In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2, promoting SREBF2/SREBP2-dependent cholesterol biosynthesis (By similarity). SREBF2/SREBP2-dependent cholesterol biosynthesis participates to myelinization and is required for eye lens transparency (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:22398723, ECO:0000269|PubMed:31829086, ECO:0000269|PubMed:34428287}.; FUNCTION: [Isoform QKI6]: Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (PubMed:37379838). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation (PubMed:37379838). Acts as a translational repressor for HNRNPA1 and GLI1 (By similarity). Translation inhibition of HNRNPA1 during oligodendrocyte differentiation prevents inclusion of exon 12 in MAG pre-mRNA splicing (By similarity). Involved in astrocyte differentiation by regulating translation of target mRNAs (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:37379838}.; FUNCTION: [Isoform QKI7]: Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (PubMed:37379838). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation (PubMed:37379838). Acts as a negative regulator of angiogenesis by binding to mRNAs encoding CDH5, NLGN1 and TNFAIP6, promoting their degradation (PubMed:32732889). Can also induce apoptosis in the cytoplasm (By similarity). Heterodimerization with other isoforms results in nuclear translocation of isoform QKI7 and suppression of apoptosis (By similarity). Also binds some microRNAs: promotes stabilitation of miR-122 by mediating recruitment of poly(A) RNA polymerase TENT2, leading to 3' adenylation and stabilization of miR-122 (PubMed:31792053). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:31792053, ECO:0000269|PubMed:32732889, ECO:0000269|PubMed:37379838}. |
| Q96PV0 | SYNGAP1 | S895 | ochoa | Ras/Rap GTPase-activating protein SynGAP (Neuronal RasGAP) (Synaptic Ras GTPase-activating protein 1) (Synaptic Ras-GAP 1) | Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. Exhibits dual GTPase-activating specificity for Ras and Rap. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits (By similarity). {ECO:0000250}. |
| Q96PY6 | NEK1 | S418 | psp | Serine/threonine-protein kinase Nek1 (EC 2.7.11.1) (Never in mitosis A-related kinase 1) (NimA-related protein kinase 1) (Renal carcinoma antigen NY-REN-55) | Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}. |
| Q96PY6 | NEK1 | S428 | ochoa | Serine/threonine-protein kinase Nek1 (EC 2.7.11.1) (Never in mitosis A-related kinase 1) (NimA-related protein kinase 1) (Renal carcinoma antigen NY-REN-55) | Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}. |
| Q96Q15 | SMG1 | S94 | ochoa | Serine/threonine-protein kinase SMG1 (SMG-1) (hSMG-1) (EC 2.7.11.1) (Lambda/iota protein kinase C-interacting protein) (Lambda-interacting protein) (Nonsense mediated mRNA decay-associated PI3K-related kinase SMG1) | Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154, ECO:0000269|PubMed:16452507}. |
| Q96QC0 | PPP1R10 | S545 | ochoa | Serine/threonine-protein phosphatase 1 regulatory subunit 10 (MHC class I region proline-rich protein CAT53) (PP1-binding protein of 114 kDa) (Phosphatase 1 nuclear targeting subunit) (p99) | Substrate-recognition component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation (PubMed:39603239, PubMed:39603240). Promoter-proximal pausing by RNA polymerase II is a transcription halt following transcription initiation but prior to elongation, which acts as a checkpoint to control that transcripts are favorably configured for transcriptional elongation (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex also regulates RNA polymerase II transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription (PubMed:31677974). PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at 'Ser-5' of the CTD, promoting RNA polymerase II degradation (PubMed:33264625). The PNUTS-PP1 complex also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (By similarity). PNUTS-PP1 complex mediates dephosphorylation of MYC, promoting MYC stability by preventing MYC ubiquitination by the SCF(FBXW7) complex (PubMed:30158517). In addition to acts as a substrate-recognition component, PPP1R10/PNUTS also acts as a nuclear targeting subunit for the PNUTS-PP1 complex (PubMed:9450550). In some context, PPP1R10/PNUTS also acts as an inhibitor of protein phosphatase 1 (PP1) activity by preventing access to substrates, such as RB (PubMed:18360108). {ECO:0000250|UniProtKB:Q80W00, ECO:0000269|PubMed:18360108, ECO:0000269|PubMed:30158517, ECO:0000269|PubMed:31677974, ECO:0000269|PubMed:33264625, ECO:0000269|PubMed:39603239, ECO:0000269|PubMed:39603240, ECO:0000269|PubMed:9450550}. |
| Q96RY5 | CRAMP1 | S110 | ochoa | Protein cramped-like (Cramped chromatin regulator homolog 1) (Hematological and neurological expressed 1-like protein) | None |
| Q96SB4 | SRPK1 | S51 | ochoa|psp | SRSF protein kinase 1 (EC 2.7.11.1) (SFRS protein kinase 1) (Serine/arginine-rich protein-specific kinase 1) (SR-protein-specific kinase 1) | Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. {ECO:0000269|PubMed:10049757, ECO:0000269|PubMed:10390541, ECO:0000269|PubMed:11509566, ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:15034300, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:16209947, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19240134, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675, ECO:0000269|PubMed:20708644, ECO:0000269|PubMed:8208298, ECO:0000269|PubMed:9237760}. |
| Q96SD1 | DCLRE1C | S548 | psp | Protein artemis (EC 3.1.-.-) (DNA cross-link repair 1C protein) (Protein A-SCID) (SNM1 homolog C) (hSNM1C) (SNM1-like protein) | Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination (PubMed:11336668, PubMed:11955432, PubMed:12055248, PubMed:14744996, PubMed:15071507, PubMed:15574326, PubMed:15936993). Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments (PubMed:11336668, PubMed:11955432, PubMed:14744996). V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs) (PubMed:11336668, PubMed:11955432, PubMed:14744996). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends (PubMed:11336668, PubMed:11955432, PubMed:14744996). These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively (PubMed:11336668, PubMed:11955432, PubMed:14744996). This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC (PubMed:11955432, PubMed:15071507, PubMed:15574326, PubMed:15936993). The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint (PubMed:11955432). Also required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ (PubMed:15456891, PubMed:15468306, PubMed:15574327, PubMed:15811628). {ECO:0000269|PubMed:11336668, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12055248, ECO:0000269|PubMed:14744996, ECO:0000269|PubMed:15071507, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15468306, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:15574327, ECO:0000269|PubMed:15811628, ECO:0000269|PubMed:15936993}. |
| Q96SN8 | CDK5RAP2 | S140 | psp | CDK5 regulatory subunit-associated protein 2 (CDK5 activator-binding protein C48) (Centrosome-associated protein 215) | Potential regulator of CDK5 activity via its interaction with CDK5R1 (PubMed:15164053). Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter (PubMed:19282672). Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends (PubMed:18042621, PubMed:17959831, PubMed:19553473). Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gTuRC) onto centrosomes (PubMed:18042621, PubMed:17959831, PubMed:26485573, PubMed:39321809). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q8K389, ECO:0000269|PubMed:15164053, ECO:0000269|PubMed:17959831, ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697, ECO:0000269|PubMed:39321809}. |
| Q96T23 | RSF1 | S1359 | ochoa|psp | Remodeling and spacing factor 1 (Rsf-1) (HBV pX-associated protein 8) (Hepatitis B virus X-associated protein) (p325 subunit of RSF chromatin-remodeling complex) | Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF-alpha induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984). {ECO:0000269|PubMed:11788598, ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:28801535}. |
| Q96T37 | RBM15 | S109 | ochoa | RNA-binding protein 15 (One-twenty two protein 1) (RNA-binding motif protein 15) | RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (By similarity). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495). May be implicated in HOX gene regulation (PubMed:11344311). {ECO:0000250|UniProtKB:Q0VBL3, ECO:0000269|PubMed:17001072, ECO:0000269|PubMed:19786495, ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:27602518, ECO:0000305|PubMed:11344311}. |
| Q96T37 | RBM15 | S210 | ochoa | RNA-binding protein 15 (One-twenty two protein 1) (RNA-binding motif protein 15) | RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (By similarity). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495). May be implicated in HOX gene regulation (PubMed:11344311). {ECO:0000250|UniProtKB:Q0VBL3, ECO:0000269|PubMed:17001072, ECO:0000269|PubMed:19786495, ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:27602518, ECO:0000305|PubMed:11344311}. |
| Q96T37 | RBM15 | S212 | ochoa | RNA-binding protein 15 (One-twenty two protein 1) (RNA-binding motif protein 15) | RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (By similarity). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495). May be implicated in HOX gene regulation (PubMed:11344311). {ECO:0000250|UniProtKB:Q0VBL3, ECO:0000269|PubMed:17001072, ECO:0000269|PubMed:19786495, ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:27602518, ECO:0000305|PubMed:11344311}. |
| Q96T58 | SPEN | S1261 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96TC7 | RMDN3 | S232 | ochoa | Regulator of microtubule dynamics protein 3 (RMD-3) (hRMD-3) (Cerebral protein 10) (Protein FAM82A2) (Protein FAM82C) (Protein tyrosine phosphatase-interacting protein 51) (TCPTP-interacting protein 51) | Involved in cellular calcium homeostasis regulation. May participate in differentiation and apoptosis of keratinocytes. Overexpression induces apoptosis. {ECO:0000269|PubMed:16820967, ECO:0000269|PubMed:22131369}. |
| Q99081 | TCF12 | S332 | ochoa | Transcription factor 12 (TCF-12) (Class B basic helix-loop-helix protein 20) (bHLHb20) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4) | Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (By similarity). May be involved in the functional network that regulates the development of the GnRH axis (PubMed:32620954). {ECO:0000250|UniProtKB:Q61286, ECO:0000269|PubMed:32620954}. |
| Q99418 | CYTH2 | S56 | ochoa | Cytohesin-2 (ARF exchange factor) (ARF nucleotide-binding site opener) (Protein ARNO) (PH, SEC7 and coiled-coil domain-containing protein 2) | Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Activates ARF factors through replacement of GDP with GTP (By similarity). The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane (PubMed:17398095). Involved in neurite growth (By similarity). {ECO:0000250|UniProtKB:P63034, ECO:0000269|PubMed:17398095}. |
| Q99442 | SEC62 | S335 | ochoa | Translocation protein SEC62 (Translocation protein 1) (TP-1) (hTP-1) | Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen. {ECO:0000269|PubMed:22375059, ECO:0000269|PubMed:29719251}. |
| Q99496 | RNF2 | S168 | ochoa | E3 ubiquitin-protein ligase RING2 (EC 2.3.2.27) (Huntingtin-interacting protein 2-interacting protein 3) (HIP2-interacting protein 3) (Protein DinG) (RING finger protein 1B) (RING1b) (RING finger protein 2) (RING finger protein BAP-1) (RING-type E3 ubiquitin transferase RING2) | E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation (PubMed:15386022, PubMed:16359901, PubMed:21772249, PubMed:25355358, PubMed:25519132, PubMed:26151332, PubMed:33864376). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation (By similarity). Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:16359901, PubMed:26151332). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:26151332). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:21772249). Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (Probable). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes (By similarity). Also acts as a negative regulator of autophagy by mediating ubiquitination of AMBRA1, leading to its subsequent degradation (By similarity). {ECO:0000250|UniProtKB:Q9CQJ4, ECO:0000269|PubMed:11513855, ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:16359901, ECO:0000269|PubMed:16714294, ECO:0000269|PubMed:20696397, ECO:0000269|PubMed:21772249, ECO:0000269|PubMed:25355358, ECO:0000269|PubMed:25519132, ECO:0000269|PubMed:26151332, ECO:0000269|PubMed:33864376, ECO:0000305}. |
| Q99638 | RAD9A | S368 | ochoa | Cell cycle checkpoint control protein RAD9A (hRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A) | Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10713044, PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:21659603). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). RAD9A possesses 3'->5' double stranded DNA exonuclease activity (PubMed:10713044). {ECO:0000269|PubMed:10713044, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:31135337}. |
| Q99640 | PKMYT1 | S160 | ochoa | Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (EC 2.7.11.1) (Myt1 kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins (PubMed:10373560, PubMed:10504341, PubMed:9001210, PubMed:9268380). Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation (PubMed:9001210, PubMed:9268380). May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect (PubMed:9001210, PubMed:9268380). {ECO:0000269|PubMed:10373560, ECO:0000269|PubMed:10504341, ECO:0000269|PubMed:9001210, ECO:0000269|PubMed:9268380}. |
| Q99666 | RGPD5 | S1223 | ochoa | RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) | None |
| Q99698 | LYST | S2152 | ochoa | Lysosomal-trafficking regulator (Beige homolog) | Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (PubMed:11984006, PubMed:25216107). Might regulate trafficking of effectors involved in exocytosis (PubMed:25425525). In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules (PubMed:26478006). In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes (By similarity). In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways (PubMed:27881733). {ECO:0000250|UniProtKB:P97412, ECO:0000269|PubMed:11984006, ECO:0000269|PubMed:25216107, ECO:0000269|PubMed:25425525, ECO:0000269|PubMed:26478006, ECO:0000269|PubMed:27881733}. |
| Q99698 | LYST | S2256 | ochoa | Lysosomal-trafficking regulator (Beige homolog) | Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (PubMed:11984006, PubMed:25216107). Might regulate trafficking of effectors involved in exocytosis (PubMed:25425525). In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules (PubMed:26478006). In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes (By similarity). In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways (PubMed:27881733). {ECO:0000250|UniProtKB:P97412, ECO:0000269|PubMed:11984006, ECO:0000269|PubMed:25216107, ECO:0000269|PubMed:25425525, ECO:0000269|PubMed:26478006, ECO:0000269|PubMed:27881733}. |
| Q99700 | ATXN2 | S642 | ochoa | Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) | Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}. |
| Q99729 | HNRNPAB | S242 | ochoa | Heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B) (APOBEC1-binding protein 1) (ABBP-1) | Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNA transcripts around the RNA editing site. |
| Q99856 | ARID3A | S101 | ochoa | AT-rich interactive domain-containing protein 3A (ARID domain-containing protein 3A) (B-cell regulator of IgH transcription) (Bright) (Dead ringer-like protein 1) (E2F-binding protein 1) | Transcription factor which may be involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation. {ECO:0000269|PubMed:11812999, ECO:0000269|PubMed:12692263}. |
| Q99952 | PTPN18 | S423 | ochoa | Tyrosine-protein phosphatase non-receptor type 18 (EC 3.1.3.48) (Brain-derived phosphatase) | Differentially dephosphorylate autophosphorylated tyrosine kinases which are known to be overexpressed in tumor tissues. |
| Q99956 | DUSP9 | S356 | ochoa | Dual specificity protein phosphatase 9 (EC 3.1.3.16) (EC 3.1.3.48) (Mitogen-activated protein kinase phosphatase 4) (MAP kinase phosphatase 4) (MKP-4) | Inactivates MAP kinases. Has a specificity for the ERK family. |
| Q99988 | GDF15 | S97 | ochoa | Growth/differentiation factor 15 (GDF-15) (Macrophage inhibitory cytokine 1) (MIC-1) (NSAID-activated gene 1 protein) (NAG-1) (NSAID-regulated gene 1 protein) (NRG-1) (Placental TGF-beta) (Placental bone morphogenetic protein) (Prostate differentiation factor) | Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (PubMed:23468844, PubMed:24971956, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:29046435, PubMed:30639358, PubMed:31875646, PubMed:33589633, PubMed:38092039). The aversive response is both required to reduce continuing exposure to those stresses at the time of exposure and to promote avoidance behavior in the future (PubMed:30639358, PubMed:33589633, PubMed:38092039). Acts by binding to its receptor, GFRAL, activating GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:31535977). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitutes part of the 'emergency circuit' that shapes responses to stressful conditions (PubMed:28953886). The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues (PubMed:31402172). Required for avoidance behavior in response to food allergens: induced downstream of mast cell activation to promote aversion and minimize harmful effects of exposure to noxious substances (By similarity). In addition to suppress appetite, also promotes weight loss by enhancing energy expenditure in muscle: acts by increasing calcium futile cycling in muscle (By similarity). Contributes to the effect of metformin, an anti-diabetic drug, on appetite reduction and weight loss: produced in the kidney in response to metformin treatment, thereby activating the GDF15-GFRAL response, leading to reduced appetite and weight (PubMed:31875646, PubMed:37060902). The contribution of GDF15 to weight loss following metformin treatment is however limited and subject to discussion (PubMed:36001956). Produced in response to anticancer drugs, such as camptothecin or cisplatin, promoting nausea, vomiting and contributing to malnutrition (By similarity). Overproduced in many cancers, promoting anorexia in cancer (cachexia) (PubMed:32661391). Responsible for the risk of nausea and vomiting during pregnancy: high levels of GDF15 during pregnancy, mostly originating from the fetus, are associated with increased nausea and vomiting (PubMed:38092039). Maternal sensitivity to nausea is probably determined by pre-pregnancy exposure to GDF15, women with naturally high level of GDF15 being less susceptible to nausea than women with low levels of GDF15 before pregnancy (PubMed:38092039). Promotes metabolic adaptation in response to systemic inflammation caused by bacterial and viral infections in order to promote tissue tolerance and prevent tissue damage (PubMed:31402172). Required for tissue tolerance in response to myocardial infarction by acting as an inhibitor of leukocyte integring activation, thereby protecting against cardiac rupture (By similarity). Inhibits growth hormone signaling on hepatocytes (By similarity). {ECO:0000250|UniProtKB:Q9Z0J7, ECO:0000269|PubMed:23468844, ECO:0000269|PubMed:24971956, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:29046435, ECO:0000269|PubMed:30639358, ECO:0000269|PubMed:31402172, ECO:0000269|PubMed:31535977, ECO:0000269|PubMed:31875646, ECO:0000269|PubMed:32661391, ECO:0000269|PubMed:33589633, ECO:0000269|PubMed:36001956, ECO:0000269|PubMed:37060902, ECO:0000269|PubMed:38092039}. |
| Q9BPU6 | DPYSL5 | S538 | ochoa | Dihydropyrimidinase-related protein 5 (DRP-5) (CRMP3-associated molecule) (CRAM) (Collapsin response mediator protein 5) (CRMP-5) (UNC33-like phosphoprotein 6) (ULIP-6) | Involved in the negative regulation of dendrite outgrowth. {ECO:0000269|PubMed:33894126}. |
| Q9BQ89 | FAM110A | S243 | ochoa | Protein FAM110A | None |
| Q9BQI5 | SGIP1 | S95 | ochoa | SH3-containing GRB2-like protein 3-interacting protein 1 (Endophilin-3-interacting protein) | May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis. {ECO:0000250|UniProtKB:Q8VD37}. |
| Q9BRD0 | BUD13 | S258 | ochoa | BUD13 homolog | Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}. |
| Q9BRQ0 | PYGO2 | S318 | ochoa | Pygopus homolog 2 | Involved in signal transduction through the Wnt pathway. |
| Q9BRR8 | GPATCH1 | S199 | ochoa | G patch domain-containing protein 1 (Evolutionarily conserved G-patch domain-containing protein) | None |
| Q9BRR8 | GPATCH1 | S203 | ochoa | G patch domain-containing protein 1 (Evolutionarily conserved G-patch domain-containing protein) | None |
| Q9BTC0 | DIDO1 | S1746 | ochoa | Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) | Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}. |
| Q9BUH8 | BEGAIN | S455 | ochoa | Brain-enriched guanylate kinase-associated protein | May sustain the structure of the postsynaptic density (PSD). |
| Q9BUL5 | PHF23 | S305 | ochoa | PHD finger protein 23 (PDH-containing protein JUNE-1) | Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria. {ECO:0000269|PubMed:25484098}. |
| Q9BVJ6 | UTP14A | S81 | ochoa | U3 small nucleolar RNA-associated protein 14 homolog A (Antigen NY-CO-16) (Serologically defined colon cancer antigen 16) | May be required for ribosome biogenesis. {ECO:0000250}. |
| Q9BVS4 | RIOK2 | S332 | ochoa | Serine/threonine-protein kinase RIO2 (EC 2.7.11.1) (RIO kinase 2) | Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in export of the 40S pre-ribosome particles (pre-40S) from the nucleus to the cytoplasm. Its kinase activity is required for the release of NOB1, PNO1 and LTV1 from the late pre-40S and the processing of 18S-E pre-rRNA to the mature 18S rRNA (PubMed:19564402). Regulates the timing of the metaphase-anaphase transition during mitotic progression, and its phosphorylation, most likely by PLK1, regulates this function (PubMed:21880710). {ECO:0000269|PubMed:16037817, ECO:0000269|PubMed:19564402, ECO:0000269|PubMed:21880710}. |
| Q9BW04 | SARG | S21 | ochoa | Specifically androgen-regulated gene protein | Putative androgen-specific receptor. {ECO:0000269|PubMed:15525603}. |
| Q9BW71 | HIRIP3 | S502 | ochoa | HIRA-interacting protein 3 | Histone chaperone that carries a H2A-H2B histone complex and facilitates its deposition onto chromatin. {ECO:0000269|PubMed:38334665, ECO:0000269|PubMed:9710638}. |
| Q9BWH6 | RPAP1 | S200 | ochoa | RNA polymerase II-associated protein 1 | Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. Required for interaction of the RNA polymerase II complex with acetylated histone H3. {ECO:0000269|PubMed:17643375}. |
| Q9BXB4 | OSBPL11 | S48 | ochoa | Oxysterol-binding protein-related protein 11 (ORP-11) (OSBP-related protein 11) | Plays a role in regulating ADIPOQ and FABP4 levels in differentiating adipocytes and is also involved in regulation of adipocyte triglyceride storage (PubMed:23028956). Weakly binds 25-hydroxycholesterol (PubMed:17428193). Interacts with OSBPL9 to function as lipid transfer proteins (PubMed:39106189). Together they form a heterodimer that localizes at the ER-trans-Golgi membrane contact sites, and exchanges phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) for phosphatidylinositol-4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), PI(4)P) between the two organelles, a step that is critical for sphingomyelin synthesis in the Golgi complex (PubMed:39106189). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:23028956, ECO:0000269|PubMed:39106189}. |
| Q9BXB5 | OSBPL10 | S265 | ochoa | Oxysterol-binding protein-related protein 10 (ORP-10) (OSBP-related protein 10) | Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable) (PubMed:23934110). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:19554302, ECO:0000269|PubMed:22906437, ECO:0000269|PubMed:23934110, ECO:0000305}. |
| Q9BXI6 | TBC1D10A | S64 | ochoa | TBC1 domain family member 10A (EBP50-PDX interactor of 64 kDa) (EPI64 protein) (Rab27A-GAP-alpha) | GTPase-activating protein (GAP) specific for RAB27A and RAB35 (PubMed:16923811, PubMed:30905672). Does not show GAP activity for RAB2A, RAB3A and RAB4A (PubMed:16923811). {ECO:0000269|PubMed:16923811, ECO:0000269|PubMed:30905672}. |
| Q9BXP5 | SRRT | S579 | ochoa | Serrate RNA effector molecule homolog (Arsenite-resistance protein 2) | Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped RNA); however interaction is probably mediated via its interaction with NCBP1/CBP80 component of the CBC complex. Involved in cell cycle progression at S phase. Does not directly confer arsenite resistance but rather modulates arsenic sensitivity. Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription (By similarity). {ECO:0000250, ECO:0000269|PubMed:19632182}. |
| Q9BXW6 | OSBPL1A | S509 | ochoa | Oxysterol-binding protein-related protein 1 (ORP-1) (OSBP-related protein 1) | Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (By similarity). Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A (PubMed:16176980). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000250, ECO:0000269|PubMed:16176980, ECO:0000269|PubMed:17428193}. |
| Q9BY89 | KIAA1671 | S120 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYV8 | CEP41 | S282 | ochoa | Centrosomal protein of 41 kDa (Cep41) (Testis-specific gene A14 protein) | Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of TTLL6, a tubulin polyglutamylase, between the basal body and the cilium. {ECO:0000269|PubMed:22246503}. |
| Q9BZ29 | DOCK9 | S170 | ochoa | Dedicator of cytokinesis protein 9 (Cdc42 guanine nucleotide exchange factor zizimin-1) (Zizimin-1) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation. {ECO:0000269|PubMed:12172552, ECO:0000269|PubMed:19745154}. |
| Q9BZ29 | DOCK9 | S310 | ochoa | Dedicator of cytokinesis protein 9 (Cdc42 guanine nucleotide exchange factor zizimin-1) (Zizimin-1) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Overexpression induces filopodia formation. {ECO:0000269|PubMed:12172552, ECO:0000269|PubMed:19745154}. |
| Q9BZ72 | PITPNM2 | S1277 | ochoa | Membrane-associated phosphatidylinositol transfer protein 2 (Phosphatidylinositol transfer protein, membrane-associated 2) (PITPnm 2) (Pyk2 N-terminal domain-interacting receptor 3) (NIR-3) | Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro). Binds calcium ions. {ECO:0000269|PubMed:10022914}. |
| Q9BZ95 | NSD3 | S568 | ochoa | Histone-lysine N-methyltransferase NSD3 (EC 2.1.1.370) (EC 2.1.1.371) (Nuclear SET domain-containing protein 3) (Protein whistle) (WHSC1-like 1 isoform 9 with methyltransferase activity to lysine) (Wolf-Hirschhorn syndrome candidate 1-like protein 1) (WHSC1-like protein 1) | Histone methyltransferase. Preferentially dimethylates 'Lys-4' and 'Lys-27' of histone H3 forming H3K4me2 and H3K27me2. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression. {ECO:0000269|PubMed:16682010}. |
| Q9C0C2 | TNKS1BP1 | S1024 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S1452 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C9 | UBE2O | S73 | ochoa | (E3-independent) E2 ubiquitin-conjugating enzyme (EC 2.3.2.24) (E2/E3 hybrid ubiquitin-protein ligase UBE2O) (Ubiquitin carrier protein O) (Ubiquitin-conjugating enzyme E2 O) (Ubiquitin-conjugating enzyme E2 of 230 kDa) (Ubiquitin-conjugating enzyme E2-230K) (Ubiquitin-protein ligase O) | E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). {ECO:0000269|PubMed:23381138, ECO:0000269|PubMed:23452853, ECO:0000269|PubMed:23455153, ECO:0000269|PubMed:24703950}. |
| Q9C0C9 | UBE2O | S98 | ochoa | (E3-independent) E2 ubiquitin-conjugating enzyme (EC 2.3.2.24) (E2/E3 hybrid ubiquitin-protein ligase UBE2O) (Ubiquitin carrier protein O) (Ubiquitin-conjugating enzyme E2 O) (Ubiquitin-conjugating enzyme E2 of 230 kDa) (Ubiquitin-conjugating enzyme E2-230K) (Ubiquitin-protein ligase O) | E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). {ECO:0000269|PubMed:23381138, ECO:0000269|PubMed:23452853, ECO:0000269|PubMed:23455153, ECO:0000269|PubMed:24703950}. |
| Q9C0D5 | TANC1 | S22 | ochoa | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9C0D5 | TANC1 | S1542 | ochoa | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9GZT9 | EGLN1 | S61 | psp | Egl nine homolog 1 (EC 1.14.11.29) (Hypoxia-inducible factor prolyl hydroxylase 2) (HIF-PH2) (HIF-prolyl hydroxylase 2) (HPH-2) (Prolyl hydroxylase domain-containing protein 2) (PHD2) (SM-20) | Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:12351678, ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:21792862, ECO:0000269|PubMed:25129147}. |
| Q9GZU1 | MCOLN1 | S559 | ochoa|psp | Mucolipin-1 (ML1) (MG-2) (Mucolipidin) (Transient receptor potential channel mucolipin 1) (TRPML1) | Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis (PubMed:11013137, PubMed:12459486, PubMed:14749347, PubMed:15336987, PubMed:18794901, PubMed:25720963, PubMed:27623384, PubMed:29019983). Acts as a Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:25720963, PubMed:29019983). Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy (PubMed:11013137, PubMed:12459486, PubMed:14749347, PubMed:15336987, PubMed:25720963, PubMed:27623384, PubMed:29019983). Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (By similarity). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events (PubMed:16978393). By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:25720963, PubMed:25733853, PubMed:27787197). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (PubMed:27357649). Also functions as a Fe(2+) permeable channel in late endosomes and lysosomes (PubMed:18794901). Also permeable to Mg(2+), Na(+). K(+) and Cs(+) (By similarity). Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (PubMed:25130899) In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity). {ECO:0000250|UniProtKB:Q99J21, ECO:0000269|PubMed:12459486, ECO:0000269|PubMed:14749347, ECO:0000269|PubMed:15336987, ECO:0000269|PubMed:16978393, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:25130899, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:25733853, ECO:0000269|PubMed:27357649, ECO:0000269|PubMed:27623384, ECO:0000269|PubMed:27787197, ECO:0000269|PubMed:29019983, ECO:0000305|PubMed:11013137}.; FUNCTION: May contribute to cellular lipase activity within the late endosomal pathway or at the cell surface which may be involved in processes of membrane reshaping and vesiculation, especially the growth of tubular structures. However, it is not known, whether it conveys the enzymatic activity directly, or merely facilitates the activity of an associated phospholipase. {ECO:0000305|PubMed:21256127}. |
| Q9GZV5 | WWTR1 | S60 | ochoa | WW domain-containing transcription regulator protein 1 (Transcriptional coactivator with PDZ-binding motif) | Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:11118213, PubMed:18227151, PubMed:23911299). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18227151). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (PubMed:19010321). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (PubMed:18568018). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (PubMed:18227151, PubMed:18568018). {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:18227151, ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321, ECO:0000269|PubMed:23911299}. |
| Q9GZY8 | MFF | S258 | ochoa | Mitochondrial fission factor | Plays a role in mitochondrial and peroxisomal fission (PubMed:18353969, PubMed:23530241, PubMed:24196833). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface (PubMed:23530241). May be involved in regulation of synaptic vesicle membrane dynamics by recruitment of DNM1L to clathrin-containing vesicles (By similarity). {ECO:0000250|UniProtKB:Q4KM98, ECO:0000269|PubMed:18353969, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:24196833}. |
| Q9H000 | MKRN2 | S132 | ochoa | E3 ubiquitin-protein ligase makorin-2 (EC 2.3.2.27) (RING finger protein 62) (RING-type E3 ubiquitin transferase makorin-2) | E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (By similarity). Promotes the polyubiquitination and proteasome-dependent degradation of RELA/p65, thereby suppressing RELA-mediated NF-kappaB transactivation and negatively regulating inflammatory responses (By similarity). Plays a role in the regulation of spermiation and in male fertility (By similarity). {ECO:0000250|UniProtKB:Q9ERV1}. |
| Q9H0B6 | KLC2 | S537 | ochoa | Kinesin light chain 2 (KLC 2) | Kinesin is a microtubule-associated force-producing protein that plays a role in organelle transport. The light chain functions in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (Probable). Through binding with PLEKHM2 and ARL8B, recruits kinesin-1 to lysosomes and hence direct lysosomes movement toward microtubule plus ends (PubMed:22172677). {ECO:0000269|PubMed:22172677, ECO:0000305|PubMed:22172677}. |
| Q9H0R3 | TMEM222 | S40 | ochoa | Transmembrane protein 222 | None |
| Q9H0W5 | CCDC8 | S401 | ochoa | Coiled-coil domain-containing protein 8 | Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696). Required for localization of CUL7 to the centrosome (PubMed:24793695). {ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}. |
| Q9H0W8 | SMG9 | S25 | ochoa | Nonsense-mediated mRNA decay factor SMG9 | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:19417104). Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8 (PubMed:19417104). Plays a role in brain, heart, and eye development (By similarity). {ECO:0000250|UniProtKB:Q9DB90, ECO:0000269|PubMed:19417104}. |
| Q9H0X9 | OSBPL5 | S327 | ochoa | Oxysterol-binding protein-related protein 5 (ORP-5) (OSBP-related protein 5) (Oxysterol-binding protein homolog 1) | Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:23934110, PubMed:26206935). May cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes (PubMed:21220512). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:21220512, ECO:0000269|PubMed:23934110, ECO:0000269|PubMed:26206935}. |
| Q9H1A4 | ANAPC1 | S60 | ochoa | Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9H201 | EPN3 | S163 | ochoa | Epsin-3 (EPS-15-interacting protein 3) | None |
| Q9H201 | EPN3 | S182 | ochoa | Epsin-3 (EPS-15-interacting protein 3) | None |
| Q9H2G2 | SLK | S667 | ochoa | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q9H2K8 | TAOK3 | S168 | ochoa | Serine/threonine-protein kinase TAO3 (EC 2.7.11.1) (Cutaneous T-cell lymphoma-associated antigen HD-CL-09) (CTCL-associated antigen HD-CL-09) (Dendritic cell-derived protein kinase) (JNK/SAPK-inhibitory kinase) (Jun kinase-inhibitory kinase) (Kinase from chicken homolog A) (hKFC-A) (Thousand and one amino acid protein 3) | Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of the MAPK8/JNK cascade and diminishes its activation in response to epidermal growth factor (EGF). Positively regulates canonical T cell receptor (TCR) signaling by preventing early PTPN6/SHP1-mediated inactivation of LCK, ensuring sustained TCR signaling that is required for optimal activation and differentiation of T cells (PubMed:30373850). Phosphorylates PTPN6/SHP1 on 'Thr-394', leading to its polyubiquitination and subsequent proteasomal degradation (PubMed:38166031). Required for cell surface expression of metalloprotease ADAM10 on type 1 transitional B cells which is necessary for their NOTCH-mediated development into marginal zone B cells (By similarity). Also required for the NOTCH-mediated terminal differentiation of splenic conventional type 2 dendritic cells (By similarity). Positively regulates osteoblast differentiation by acting as an upstream activator of the JNK pathway (PubMed:32807497). Promotes JNK signaling in hepatocytes and positively regulates hepatocyte lipid storage by inhibiting beta-oxidation and triacylglycerol secretion while enhancing lipid synthesis (PubMed:34634521). Restricts age-associated inflammation by negatively regulating differentiation of macrophages and their production of pro-inflammatory cytokines (By similarity). Plays a role in negatively regulating the abundance of regulatory T cells in white adipose tissue (By similarity). {ECO:0000250|UniProtKB:Q8BYC6, ECO:0000269|PubMed:10559204, ECO:0000269|PubMed:10924369, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:30373850, ECO:0000269|PubMed:32807497, ECO:0000269|PubMed:34634521, ECO:0000269|PubMed:38166031}. |
| Q9H2Y7 | ZNF106 | S1304 | ochoa | Zinc finger protein 106 (Zfp-106) (Zinc finger protein 474) | RNA-binding protein. Specifically binds to 5'-GGGGCC-3' sequence repeats in RNA. Essential for maintenance of peripheral motor neuron and skeletal muscle function. Required for normal expression and/or alternative splicing of a number of genes in spinal cord and skeletal muscle, including the neurite outgrowth inhibitor RTN4. Also contributes to normal mitochondrial respiratory function in motor neurons, via an unknown mechanism. {ECO:0000250|UniProtKB:O88466}. |
| Q9H4A3 | WNK1 | S185 | ochoa | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9H4A3 | WNK1 | S189 | ochoa | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9H4A3 | WNK1 | S2270 | ochoa | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9H4B7 | TUBB1 | S35 | ochoa | Tubulin beta-1 chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9H4E7 | DEF6 | S590 | ochoa | Differentially expressed in FDCP 6 homolog (DEF-6) (IRF4-binding protein) | Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42 (PubMed:12651066, PubMed:15023524). Can regulate cell morphology in cooperation with activated RAC1 (By similarity). Involved in immune homeostasis by ensuring proper trafficking and availability of T-cell regulator CTLA-4 at T-cell surface (PubMed:31308374). Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling (By similarity). {ECO:0000250|UniProtKB:Q8C2K1, ECO:0000269|PubMed:12651066, ECO:0000269|PubMed:15023524, ECO:0000269|PubMed:31308374}. |
| Q9H4G0 | EPB41L1 | S564 | ochoa | Band 4.1-like protein 1 (Erythrocyte membrane protein band 4.1-like 1) (Neuronal protein 4.1) (4.1N) | May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases. |
| Q9H4L5 | OSBPL3 | S30 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H4L5 | OSBPL3 | S166 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H4L5 | OSBPL3 | S764 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H694 | BICC1 | S31 | ochoa | Protein bicaudal C homolog 1 (Bic-C) | Putative RNA-binding protein. Acts as a negative regulator of Wnt signaling. May be involved in regulating gene expression during embryonic development. {ECO:0000269|PubMed:21922595}. |
| Q9H6I2 | SOX17 | S302 | ochoa | Transcription factor SOX-17 | Acts as a transcription regulator that binds target promoter DNA and bends the DNA. Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key role in the regulation of embryonic development. Required for normal development of the definitive gut endoderm. Required for normal looping of the embryonic heart tube. Plays an important role in embryonic and postnatal vascular development, including development of arteries. Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX18. Required for the generation and maintenance of fetal hematopoietic stem cells, and for fetal hematopoiesis. Probable transcriptional activator in the premeiotic germ cells. {ECO:0000250|UniProtKB:Q61473}. |
| Q9H6U6 | BCAS3 | S838 | ochoa | BCAS3 microtubule associated cell migration factor (Breast carcinoma-amplified sequence 3) (GAOB1) | Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation (By similarity). Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy (PubMed:33499712). Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures (PubMed:33499712). {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058, ECO:0000269|PubMed:33499712}. |
| Q9H6U6 | BCAS3 | S877 | ochoa | BCAS3 microtubule associated cell migration factor (Breast carcinoma-amplified sequence 3) (GAOB1) | Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation (By similarity). Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy (PubMed:33499712). Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures (PubMed:33499712). {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058, ECO:0000269|PubMed:33499712}. |
| Q9H792 | PEAK1 | S214 | ochoa | Inactive tyrosine-protein kinase PEAK1 (Pseudopodium-enriched atypical kinase 1) (Sugen kinase 269) (Tyrosine-protein kinase SgK269) | Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics (PubMed:20534451, PubMed:23105102, PubMed:35687021). Acts as a scaffold for mediating EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654, ECO:0000269|PubMed:35687021}. |
| Q9H7N4 | SCAF1 | S659 | ochoa | Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) | May function in pre-mRNA splicing. {ECO:0000250}. |
| Q9H7N4 | SCAF1 | S933 | ochoa | Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) | May function in pre-mRNA splicing. {ECO:0000250}. |
| Q9H7N4 | SCAF1 | S936 | ochoa | Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) | May function in pre-mRNA splicing. {ECO:0000250}. |
| Q9H875 | PRKRIP1 | S76 | ochoa | PRKR-interacting protein 1 | Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:30705154). Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity (By similarity). {ECO:0000250|UniProtKB:Q9CWV6, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:30705154}. |
| Q9H8S9 | MOB1A | S38 | ochoa | MOB kinase activator 1A (Mob1 alpha) (Mob1A) (Mob1 homolog 1B) (Mps one binder kinase activator-like 1B) | Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38. {ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19739119}. |
| Q9H8V3 | ECT2 | S861 | ochoa | Protein ECT2 (Epithelial cell-transforming sequence 2 oncogene) | Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}. |
| Q9H8Y5 | ANKZF1 | S51 | ochoa | tRNA endonuclease ANKZF1 (EC 3.1.-.-) (Ankyrin repeat and zinc finger domain-containing protein 1) (Zinc finger protein 744) | Endonuclease that cleaves polypeptidyl-tRNAs downstream of the ribosome-associated quality control (RQC) pathway to release incompletely synthesized polypeptides for degradation (PubMed:29632312, PubMed:30244831, PubMed:31011209). The RQC pathway disassembles aberrantly stalled translation complexes to recycle or degrade the constituent parts (PubMed:29632312, PubMed:30244831, PubMed:31011209). ANKZF1 acts downstream disassembly of stalled ribosomes and specifically cleaves off the terminal 3'-CCA nucleotides universal to all tRNAs from polypeptidyl-tRNAs, releasing (1) ubiquitinated polypeptides from 60S ribosomal subunit for degradation and (2) cleaved tRNAs (PubMed:31011209). ANKZF1-cleaved tRNAs are then repaired and recycled by ELAC1 and TRNT1 (PubMed:31011209, PubMed:32075755). Also plays a role in the cellular response to hydrogen peroxide and in the maintenance of mitochondrial integrity under conditions of cellular stress (PubMed:28302725). {ECO:0000269|PubMed:28302725, ECO:0000269|PubMed:29632312, ECO:0000269|PubMed:30244831, ECO:0000269|PubMed:31011209, ECO:0000269|PubMed:32075755}. |
| Q9H910 | JPT2 | S144 | ochoa | Jupiter microtubule associated homolog 2 (Hematological and neurological expressed 1-like protein) (HN1-like protein) | Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein required for NAADP-evoked intracellular calcium release (PubMed:33758061, PubMed:33758062). Confers NAADP-sensitivity to the two pore channels (TPCs) complex (PubMed:33758061). Enables NAADP to activate Ca(2+) release from the endoplasmic reticulum through ryanodine receptors (PubMed:33758062). {ECO:0000269|PubMed:33758061, ECO:0000269|PubMed:33758062}.; FUNCTION: (Microbial infection) Involved in the endolysosomal trafficking of human coronavirus SARS-CoV-2. {ECO:0000269|PubMed:33758061}. |
| Q9H9B1 | EHMT1 | S38 | ochoa | Histone-lysine N-methyltransferase EHMT1 (EC 2.1.1.-) (EC 2.1.1.367) (Euchromatic histone-lysine N-methyltransferase 1) (Eu-HMTase1) (G9a-like protein 1) (GLP) (GLP1) (Histone H3-K9 methyltransferase 5) (H3-K9-HMTase 5) (Lysine N-methyltransferase 1D) | Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with probable chromatin reader BAZ2B (By similarity). {ECO:0000250|UniProtKB:Q5DW34, ECO:0000269|PubMed:12004135, ECO:0000269|PubMed:20118233}. |
| Q9HAW4 | CLSPN | S34 | psp | Claspin (hClaspin) | Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| Q9HAZ1 | CLK4 | S326 | ochoa | Dual specificity protein kinase CLK4 (EC 2.7.12.1) (CDC-like kinase 4) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:11170754, ECO:0000269|PubMed:19168442}. |
| Q9HB19 | PLEKHA2 | S320 | ochoa | Pleckstrin homology domain-containing family A member 2 (PH domain-containing family A member 2) (Tandem PH domain-containing protein 2) (TAPP-2) | Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane (By similarity). {ECO:0000250}. |
| Q9HBE1 | PATZ1 | S282 | ochoa | POZ-, AT hook-, and zinc finger-containing protein 1 (BTB/POZ domain zinc finger transcription factor) (Protein kinase A RI subunit alpha-associated protein) (Zinc finger and BTB domain-containing protein 19) (Zinc finger protein 278) (Zinc finger sarcoma gene protein) | Transcriptional regulator that plays a role in many biological processes such as embryogenesis, senescence, T-cell development or neurogenesis (PubMed:10713105, PubMed:25755280, PubMed:31875552). Interacts with the TP53 protein to control genes that are important in proliferation and in the DNA-damage response. Mechanistically, the interaction inhibits the DNA binding and transcriptional activity of TP53/p53 (PubMed:25755280). Part of the transcriptional network modulating regulatory T-cell development and controls the generation of the regulatory T-cell pool under homeostatic conditions (PubMed:31875552). {ECO:0000269|PubMed:10713105, ECO:0000269|PubMed:25755280, ECO:0000269|PubMed:31875552}.; FUNCTION: (Microbial infection) Plays a positive role in viral cDNA synthesis. {ECO:0000269|PubMed:31060775}. |
| Q9HBH0 | RHOF | S64 | ochoa | Rho-related GTP-binding protein RhoF (Rho family GTPase Rif) (Rho in filopodia) | Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Causes the formation of thin, actin-rich surface projections called filopodia. Functions cooperatively with CDC42 and Rac to generate additional structures, increasing the diversity of actin-based morphology. |
| Q9HBL0 | TNS1 | S1413 | psp | Tensin-1 (EC 3.1.3.-) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in fibrillar adhesion formation (PubMed:21768292, PubMed:28005397). Essential for myofibroblast differentiation and myofibroblast-mediated extracellular matrix deposition (PubMed:28005397). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in cell polarization and migration (PubMed:19826001). May be involved in cartilage development and in linking signal transduction pathways to the cytoskeleton (PubMed:21768292). {ECO:0000269|PubMed:19826001, ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:28005397, ECO:0000305}. |
| Q9HC35 | EML4 | S87 | ochoa | Echinoderm microtubule-associated protein-like 4 (EMAP-4) (Restrictedly overexpressed proliferation-associated protein) (Ropp 120) | Essential for the formation and stability of microtubules (MTs) (PubMed:16890222, PubMed:31409757). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs (PubMed:25789526). Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression (PubMed:25789526). {ECO:0000269|PubMed:16890222, ECO:0000269|PubMed:25789526, ECO:0000269|PubMed:31409757}. |
| Q9HCD6 | TANC2 | S430 | ochoa | Protein TANC2 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2) | Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines. {ECO:0000269|PubMed:30021165}. |
| Q9HCM4 | EPB41L5 | S405 | ochoa | Band 4.1-like protein 5 (Erythrocyte membrane protein band 4.1-like 5) | Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells. {ECO:0000269|PubMed:17920587}. |
| Q9HCN4 | GPN1 | S301 | ochoa | GPN-loop GTPase 1 (EC 3.6.5.-) (MBD2-interacting protein) (MBDin) (RNAPII-associated protein 4) (XPA-binding protein 1) | Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII) (PubMed:20855544, PubMed:21768307). May act at an RNAP assembly step prior to nuclear import (PubMed:21768307). Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding proteins, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation (PubMed:17643375). May be involved in nuclear localization of XPA (PubMed:11058119). {ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:20855544, ECO:0000269|PubMed:21768307, ECO:0000305|PubMed:11058119}. |
| Q9HCS5 | EPB41L4A | S448 | ochoa | Band 4.1-like protein 4A (Erythrocyte membrane protein band 4.1-like 4A) (Protein NBL4) | None |
| Q9NPG3 | UBN1 | S336 | ochoa | Ubinuclein-1 (HIRA-binding protein) (Protein VT4) (Ubiquitously expressed nuclear protein) | Acts as a novel regulator of senescence. Involved in the formation of senescence-associated heterochromatin foci (SAHF), which represses expression of proliferation-promoting genes. Binds to proliferation-promoting genes. May be required for replication-independent chromatin assembly. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:19029251}. |
| Q9NQC1 | JADE2 | S635 | ochoa | E3 ubiquitin-protein ligase Jade-2 (EC 2.3.2.27) (Jade family PHD finger protein 2) (PHD finger protein 15) | Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity (PubMed:16387653). Acts as an E3 ubiquitin-protein ligase mediating the ubiquitination and subsequent proteasomal degradation of target protein histone demethylase KDM1A (PubMed:25018020). Also acts as a ubiquitin ligase E3 toward itself. Positive regulator of neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q6ZQF7, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:25018020}. |
| Q9NQW6 | ANLN | S664 | ochoa | Anillin | Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}. |
| Q9NR09 | BIRC6 | S1866 | ochoa | Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 (EC 2.3.2.24) (BIR repeat-containing ubiquitin-conjugating enzyme) (BRUCE) (Baculoviral IAP repeat-containing protein 6) (Ubiquitin-conjugating BIR domain enzyme apollon) (APOLLON) | Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase (PubMed:14765125, PubMed:15200957, PubMed:18329369). Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6 (PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2 (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases (PubMed:18329369, PubMed:36758106). Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC (PubMed:36758105). Important regulator for the final stages of cytokinesis (PubMed:18329369). Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification (PubMed:18329369). {ECO:0000269|PubMed:14765125, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:18329369, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}. |
| Q9NR45 | NANS | S134 | ochoa | N-acetylneuraminate-9-phosphate synthase (EC 2.5.1.57) (3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase) (EC 2.5.1.132) (N-acetylneuraminic acid phosphate synthase) (NANS) (Sialic acid phosphate synthase) (Sialic acid synthase) | Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) (PubMed:10749855). Also catalyzes the condensation of PEP and D-mannose 6-phosphate (Man-6-P) to produce 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate (KDN-9-P) (PubMed:10749855). Neu5Ac-9-P and KDN-9-P are the phosphorylated forms of sialic acids N-acetylneuraminic acid (Neu5Ac) and deaminoneuraminic acid (KDN), respectively (PubMed:10749855). Required for brain and skeletal development (PubMed:27213289). {ECO:0000269|PubMed:10749855, ECO:0000269|PubMed:27213289}. |
| Q9NR45 | NANS | S248 | ochoa | N-acetylneuraminate-9-phosphate synthase (EC 2.5.1.57) (3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase) (EC 2.5.1.132) (N-acetylneuraminic acid phosphate synthase) (NANS) (Sialic acid phosphate synthase) (Sialic acid synthase) | Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) (PubMed:10749855). Also catalyzes the condensation of PEP and D-mannose 6-phosphate (Man-6-P) to produce 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate (KDN-9-P) (PubMed:10749855). Neu5Ac-9-P and KDN-9-P are the phosphorylated forms of sialic acids N-acetylneuraminic acid (Neu5Ac) and deaminoneuraminic acid (KDN), respectively (PubMed:10749855). Required for brain and skeletal development (PubMed:27213289). {ECO:0000269|PubMed:10749855, ECO:0000269|PubMed:27213289}. |
| Q9NRR5 | UBQLN4 | S133 | ochoa | Ubiquilin-4 (Ataxin-1 interacting ubiquitin-like protein) (A1Up) (Ataxin-1 ubiquitin-like-interacting protein A1U) (Connexin43-interacting protein of 75 kDa) (CIP75) | Regulator of protein degradation that mediates the proteasomal targeting of misfolded, mislocalized or accumulated proteins (PubMed:15280365, PubMed:27113755, PubMed:29666234, PubMed:30612738). Acts by binding polyubiquitin chains of target proteins via its UBA domain and by interacting with subunits of the proteasome via its ubiquitin-like domain (PubMed:15280365, PubMed:27113755, PubMed:30612738). Key regulator of DNA repair that represses homologous recombination repair: in response to DNA damage, recruited to sites of DNA damage following phosphorylation by ATM and acts by binding and removing ubiquitinated MRE11 from damaged chromatin, leading to MRE11 degradation by the proteasome (PubMed:30612738). MRE11 degradation prevents homologous recombination repair, redirecting double-strand break repair toward non-homologous end joining (NHEJ) (PubMed:30612738). Specifically recognizes and binds mislocalized transmembrane-containing proteins and targets them to proteasomal degradation (PubMed:27113755). Collaborates with DESI1/POST in the export of ubiquitinated proteins from the nucleus to the cytoplasm (PubMed:29666234). Also plays a role in the regulation of the proteasomal degradation of non-ubiquitinated GJA1 (By similarity). Acts as an adapter protein that recruits UBQLN1 to the autophagy machinery (PubMed:23459205). Mediates the association of UBQLN1 with autophagosomes and the autophagy-related protein LC3 (MAP1LC3A/B/C) and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:23459205). {ECO:0000250|UniProtKB:Q99NB8, ECO:0000269|PubMed:15280365, ECO:0000269|PubMed:23459205, ECO:0000269|PubMed:27113755, ECO:0000269|PubMed:29666234, ECO:0000269|PubMed:30612738}. |
| Q9NRW1 | RAB6B | S117 | ochoa | Ras-related protein Rab-6B (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology (By similarity). Recruits VPS13B to the Golgi membrane (PubMed:25492866). Regulates the compacted morphology of the Golgi (PubMed:26209634). Seems to have a role in retrograde membrane traffic at the level of the Golgi complex. May function in retrograde transport in neuronal cells (PubMed:17707369). Plays a role in neuron projection development (PubMed:25492866). {ECO:0000250|UniProtKB:P20340, ECO:0000269|PubMed:17707369, ECO:0000269|PubMed:25492866, ECO:0000269|PubMed:26209634}. |
| Q9NUQ6 | SPATS2L | S455 | ochoa | SPATS2-like protein (DNA polymerase-transactivated protein 6) (Stress granule and nucleolar protein) (SGNP) | None |
| Q9NUQ8 | ABCF3 | S283 | ochoa | ATP-binding cassette sub-family F member 3 | Displays an antiviral effect against flaviviruses such as west Nile virus (WNV) in the presence of OAS1B. {ECO:0000250}. |
| Q9NUW8 | TDP1 | S563 | psp | Tyrosyl-DNA phosphodiesterase 1 (Tyr-DNA phosphodiesterase 1) (EC 3.1.4.-) | DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate. {ECO:0000269|PubMed:12023295, ECO:0000269|PubMed:15111055, ECO:0000269|PubMed:15811850, ECO:0000269|PubMed:16141202, ECO:0000269|PubMed:22822062}. |
| Q9NUY8 | TBC1D23 | S478 | ochoa | TBC1 domain family member 23 (HCV non-structural protein 4A-transactivated protein 1) | Putative Rab GTPase-activating protein which plays a role in vesicular trafficking (PubMed:28823707). Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197, PubMed:29426865). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). Plays a role in brain development, including in cortical neuron positioning (By similarity). May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth (By similarity). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (By similarity). {ECO:0000250|UniProtKB:Q8K0F1, ECO:0000269|PubMed:28823707, ECO:0000269|PubMed:29084197, ECO:0000269|PubMed:29426865}. |
| Q9NVE7 | PANK4 | S386 | ochoa | 4'-phosphopantetheine phosphatase (EC 3.1.3.-) (Inactive pantothenic acid kinase 4) (hPanK4) | Phosphatase which shows a preference for 4'-phosphopantetheine and its oxidatively damaged forms (sulfonate or S-sulfonate), providing strong indirect evidence that the phosphatase activity pre-empts damage in the coenzyme A (CoA) pathway (PubMed:27322068). Hydrolyzing excess 4'-phosphopantetheine could constitute a directed overflow mechanism to prevent its oxidation to the S-sulfonate, sulfonate, or other forms (PubMed:27322068). Hydrolyzing 4'-phosphopantetheine sulfonate or S-sulfonate would forestall their conversion to inactive forms of CoA and acyl carrier protein (PubMed:27322068). May play a role in the physiological regulation of CoA intracellular levels (Probable). {ECO:0000269|PubMed:27322068, ECO:0000305|PubMed:27322068}. |
| Q9NW13 | RBM28 | S644 | ochoa | RNA-binding protein 28 (RNA-binding motif protein 28) | Nucleolar component of the spliceosomal ribonucleoprotein complexes. {ECO:0000269|PubMed:17081119}. |
| Q9NWH9 | SLTM | S201 | ochoa | SAFB-like transcription modulator (Modulator of estrogen-induced transcription) | When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. {ECO:0000250}. |
| Q9NWS0 | PIH1D1 | S173 | ochoa | PIH1 domain-containing protein 1 (Nucleolar protein 17 homolog) | Involved in the assembly of C/D box small nucleolar ribonucleoprotein (snoRNP) particles (PubMed:17636026). Recruits the SWI/SNF complex to the core promoter of rRNA genes and enhances pre-rRNA transcription (PubMed:22368283, PubMed:24036451). Mediates interaction of TELO2 with the R2TP complex which is necessary for the stability of MTOR and SMG1 (PubMed:20864032). Positively regulates the assembly and activity of the mTORC1 complex (PubMed:24036451). {ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:20864032, ECO:0000269|PubMed:22368283, ECO:0000269|PubMed:24036451}. |
| Q9NX58 | LYAR | S244 | ochoa | Cell growth-regulating nucleolar protein | Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs (PubMed:24495227). Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression (PubMed:25092918). In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA (PubMed:28686580). Preferentially binds to a DNA motif containing 5'-GGTTAT-3' (PubMed:25092918). Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity (PubMed:31413131). In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines (PubMed:31413131). Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells (By similarity). Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal (By similarity). {ECO:0000250|UniProtKB:Q08288, ECO:0000269|PubMed:24495227, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:28686580, ECO:0000269|PubMed:31413131}. |
| Q9NYJ8 | TAB2 | S527 | ochoa | TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 2) (TAK1-binding protein 2) (TAB-2) (TGF-beta-activated kinase 1-binding protein 2) | Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122, PubMed:27746020, PubMed:33184450, PubMed:36681779). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122, PubMed:27746020). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:18079694, PubMed:22158122). Also recognizes and binds Lys-63'-linked polyubiquitin chains of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains (PubMed:27746020). Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (By similarity). Involved in heart development (PubMed:20493459). {ECO:0000250|UniProtKB:Q99K90, ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:15327770, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:20493459, ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:33184450, ECO:0000269|PubMed:36681779}. |
| Q9NYL2 | MAP3K20 | S685 | ochoa | Mitogen-activated protein kinase kinase kinase 20 (EC 2.7.11.25) (Human cervical cancer suppressor gene 4 protein) (HCCS-4) (Leucine zipper- and sterile alpha motif-containing kinase) (MLK-like mitogen-activated protein triple kinase) (Mitogen-activated protein kinase kinase kinase MLT) (Mixed lineage kinase 7) (Mixed lineage kinase-related kinase) (MLK-related kinase) (MRK) (Sterile alpha motif- and leucine zipper-containing kinase AZK) | Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation (PubMed:10924358, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15350844, PubMed:15737997, PubMed:18331592, PubMed:20559024, PubMed:26999302, PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JNK (MAPK8/JNK1, MAPK9/JNK2 and/or MAPK10/JNK3) and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11042189, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15172994, PubMed:15737997, PubMed:32289254, PubMed:32610081, PubMed:35857590). Activates JNK through phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7, and MAP kinase p38 gamma (MAPK12) via phosphorylation of MAP2K3/MKK3 and MAP2K6/MKK6 (PubMed:11836244, PubMed:12220515). Involved in stress associated with adrenergic stimulation: contributes to cardiac decompensation during periods of acute cardiac stress (PubMed:15350844, PubMed:21224381, PubMed:27859413). May be involved in regulation of S and G2 cell cycle checkpoint by mediating phosphorylation of CHEK2 (PubMed:15342622). {ECO:0000269|PubMed:10924358, ECO:0000269|PubMed:11042189, ECO:0000269|PubMed:11836244, ECO:0000269|PubMed:12220515, ECO:0000269|PubMed:14521931, ECO:0000269|PubMed:15172994, ECO:0000269|PubMed:15342622, ECO:0000269|PubMed:15350844, ECO:0000269|PubMed:15737997, ECO:0000269|PubMed:18331592, ECO:0000269|PubMed:20559024, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:26999302, ECO:0000269|PubMed:27859413, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}.; FUNCTION: [Isoform ZAKalpha]: Key component of the stress-activated protein kinase signaling cascade in response to ribotoxic stress or UV-B irradiation (PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts as the proximal sensor of ribosome collisions during the ribotoxic stress response (RSR): directly binds to the ribosome by inserting its flexible C-terminus into the ribosomal intersubunit space, thereby acting as a sentinel for colliding ribosomes (PubMed:32289254, PubMed:32610081). Upon ribosome collisions, activates either the stress-activated protein kinase signal transduction cascade or the integrated stress response (ISR), leading to programmed cell death or cell survival, respectively (PubMed:32610081). Dangerous levels of ribosome collisions trigger the autophosphorylation and activation of MAP3K20, which dissociates from colliding ribosomes and phosphorylates MAP kinase kinases, leading to activation of the JNK and MAP kinase p38 pathways that promote programmed cell death (PubMed:32289254, PubMed:32610081). Less dangerous levels of ribosome collisions trigger the integrated stress response (ISR): MAP3K20 activates EIF2AK4/GCN2 independently of its protein-kinase activity, promoting EIF2AK4/GCN2-mediated phosphorylation of EIF2S1/eIF-2-alpha (PubMed:32610081). Also part of the stress-activated protein kinase signaling cascade triggering the NLRP1 inflammasome in response to UV-B irradiation: ribosome collisions activate MAP3K20, which directly phosphorylates NLRP1, leading to activation of the NLRP1 inflammasome and subsequent pyroptosis (PubMed:35857590). NLRP1 is also phosphorylated by MAP kinase p38 downstream of MAP3K20 (PubMed:35857590). Also acts as a histone kinase by phosphorylating histone H3 at 'Ser-28' (H3S28ph) (PubMed:15684425). {ECO:0000269|PubMed:15684425, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}.; FUNCTION: [Isoform ZAKbeta]: Isoform that lacks the C-terminal region that mediates ribosome-binding: does not act as a sensor of ribosome collisions in response to ribotoxic stress (PubMed:32289254, PubMed:32610081, PubMed:35857590). May act as an antagonist of isoform ZAKalpha: interacts with isoform ZAKalpha, leading to decrease the expression of isoform ZAKalpha (PubMed:27859413). {ECO:0000269|PubMed:27859413, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}. |
| Q9NYQ6 | CELSR1 | S2784 | ochoa | Cadherin EGF LAG seven-pass G-type receptor 1 (Cadherin family member 9) (Flamingo homolog 2) (hFmi2) | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| Q9NYV4 | CDK12 | S29 | ochoa | Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) | Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| Q9NZB2 | FAM120A | S487 | ochoa | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q9NZM3 | ITSN2 | S1044 | ochoa | Intersectin-2 (SH3 domain-containing protein 1B) (SH3P18) (SH3P18-like WASP-associated protein) | Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:23999003}. |
| Q9NZM5 | NOP53 | S93 | ochoa | Ribosome biogenesis protein NOP53 (Glioma tumor suppressor candidate region gene 2 protein) (Protein interacting with carboxyl terminus 1) (PICT-1) (p60) | Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis (PubMed:24120868). In ribosome biogenesis, may also play a role in rRNA transcription (PubMed:27729611). Also functions as a nucleolar sensor that regulates the activation of p53/TP53 in response to ribosome biogenesis perturbation, DNA damage and other stress conditions (PubMed:21741933, PubMed:24120868, PubMed:27829214). DNA damage or perturbation of ribosome biogenesis disrupt the interaction between NOP53 and RPL11 allowing RPL11 transport to the nucleoplasm where it can inhibit MDM2 and allow p53/TP53 activation (PubMed:24120868, PubMed:27829214). It may also positively regulate the function of p53/TP53 in cell cycle arrest and apoptosis through direct interaction, preventing its MDM2-dependent ubiquitin-mediated proteasomal degradation (PubMed:22522597). Originally identified as a tumor suppressor, it may also play a role in cell proliferation and apoptosis by positively regulating the stability of PTEN, thereby antagonizing the PI3K-AKT/PKB signaling pathway (PubMed:15355975, PubMed:16971513, PubMed:27729611). May also inhibit cell proliferation and increase apoptosis through its interaction with NF2 (PubMed:21167305). May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation (PubMed:25818168). Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex (PubMed:25956029). May also regulate cellular aerobic respiration (PubMed:24556985). In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of RIGI (PubMed:27824081). {ECO:0000269|PubMed:15355975, ECO:0000269|PubMed:16971513, ECO:0000269|PubMed:21167305, ECO:0000269|PubMed:21741933, ECO:0000269|PubMed:22522597, ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:24556985, ECO:0000269|PubMed:25818168, ECO:0000269|PubMed:25956029, ECO:0000269|PubMed:27729611, ECO:0000269|PubMed:27824081, ECO:0000269|PubMed:27829214}. |
| Q9NZN4 | EHD2 | S470 | ochoa | EH domain-containing protein 2 (PAST homolog 2) | ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis (By similarity). Plays a role in membrane trafficking between the plasma membrane and endosomes (PubMed:17233914). Important for the internalization of GLUT4. Required for fusion of myoblasts to skeletal muscle myotubes. Required for normal translocation of FER1L5 to the plasma membrane (By similarity). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by constraining caveolae at the cell membrane (PubMed:25588833). {ECO:0000250|UniProtKB:Q8BH64, ECO:0000269|PubMed:17233914, ECO:0000269|PubMed:25588833}. |
| Q9NZN5 | ARHGEF12 | S22 | ochoa | Rho guanine nucleotide exchange factor 12 (Leukemia-associated RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}. |
| Q9NZN8 | CNOT2 | S242 | ochoa | CCR4-NOT transcription complex subunit 2 (CCR4-associated factor 2) | Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754, ECO:0000269|PubMed:22367759}. |
| Q9P0K8 | FOXJ2 | S38 | ochoa | Forkhead box protein J2 (Fork head homologous X) | [Isoform FOXJ2.L]: Transcriptional activator. Able to bind to two different type of DNA binding sites. More effective than isoform FOXJ2.S in transcriptional activation (PubMed:10777590, PubMed:10966786). Plays an important role in spermatogenesis, especially in spermatocyte meiosis (By similarity). {ECO:0000250|UniProtKB:Q9ES18, ECO:0000269|PubMed:10777590, ECO:0000269|PubMed:10966786}.; FUNCTION: [Isoform FOXJ2.S]: Transcriptional activator. {ECO:0000269|PubMed:10966786}. |
| Q9P0L2 | MARK1 | S463 | ochoa | Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}. |
| Q9P0L2 | MARK1 | S468 | ochoa | Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}. |
| Q9P0U4 | CXXC1 | S124 | ochoa | CXXC-type zinc finger protein 1 (CpG-binding protein) (PHD finger and CXXC domain-containing protein 1) | Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG. {ECO:0000269|PubMed:21407193}. |
| Q9P107 | GMIP | S421 | ochoa | GEM-interacting protein (GMIP) | Stimulates, in vitro and in vivo, the GTPase activity of RhoA. {ECO:0000269|PubMed:12093360}. |
| Q9P107 | GMIP | S907 | ochoa | GEM-interacting protein (GMIP) | Stimulates, in vitro and in vivo, the GTPase activity of RhoA. {ECO:0000269|PubMed:12093360}. |
| Q9P1Y5 | CAMSAP3 | S482 | ochoa | Calmodulin-regulated spectrin-associated protein 3 (Protein Nezha) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19041755, PubMed:23169647). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153). Required for the biogenesis and the maintenance of zonula adherens by anchoring the minus-end of microtubules to zonula adherens and by recruiting the kinesin KIFC3 to those junctional sites (PubMed:19041755). Required for orienting the apical-to-basal polarity of microtubules in epithelial cells: acts by tethering non-centrosomal microtubules to the apical cortex, leading to their longitudinal orientation (PubMed:26715742, PubMed:27802168). Plays a key role in early embryos, which lack centrosomes: accumulates at the microtubule bridges that connect pairs of cells and enables the formation of a non-centrosomal microtubule-organizing center that directs intracellular transport in the early embryo (By similarity). Couples non-centrosomal microtubules with actin: interaction with MACF1 at the minus ends of non-centrosomal microtubules, tethers the microtubules to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). Plays a key role in the generation of non-centrosomal microtubules by accumulating in the pericentrosomal region and cooperating with KATNA1 to release non-centrosomal microtubules from the centrosome (PubMed:28386021). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:28089391). Through interaction with AKAP9, involved in translocation of Golgi vesicles in epithelial cells, where microtubules are mainly non-centrosomal (PubMed:28089391). Plays an important role in motile cilia function by facilitatating proper orientation of basal bodies and formation of central microtubule pairs in motile cilia (By similarity). {ECO:0000250|UniProtKB:Q80VC9, ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:26715742, ECO:0000269|PubMed:27693509, ECO:0000269|PubMed:27802168, ECO:0000269|PubMed:28089391, ECO:0000269|PubMed:28386021}. |
| Q9P1Y6 | PHRF1 | S98 | ochoa | PHD and RING finger domain-containing protein 1 | None |
| Q9P219 | CCDC88C | S953 | ochoa | Protein Daple (Coiled-coil domain-containing protein 88C) (Dvl-associating protein with a high frequency of leucine residues) (hDaple) (Hook-related protein 2) (HkRP2) | Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation (PubMed:26126266). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical constriction of cells via ARHGEF18 (PubMed:30948426). {ECO:0000269|PubMed:26126266, ECO:0000269|PubMed:30948426}. |
| Q9P219 | CCDC88C | S1842 | ochoa | Protein Daple (Coiled-coil domain-containing protein 88C) (Dvl-associating protein with a high frequency of leucine residues) (hDaple) (Hook-related protein 2) (HkRP2) | Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation (PubMed:26126266). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical constriction of cells via ARHGEF18 (PubMed:30948426). {ECO:0000269|PubMed:26126266, ECO:0000269|PubMed:30948426}. |
| Q9P243 | ZFAT | S643 | ochoa | Zinc finger protein ZFAT (Zinc finger gene in AITD susceptibility region) (Zinc finger protein 406) | May be involved in transcriptional regulation. Overexpression causes down-regulation of a number of genes involved in the immune response. Some genes are also up-regulated (By similarity). {ECO:0000250}. |
| Q9P260 | RELCH | S45 | ochoa | RAB11-binding protein RELCH (LisH domain and HEAT repeat-containing protein KIAA1468) (RAB11 binding and LisH domain, coiled-coil and HEAT repeat-containing) (RAB11-binding protein containing LisH, coiled-coil, and HEAT repeats) | Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP (PubMed:29514919). Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes (PubMed:29514919). {ECO:0000269|PubMed:29514919}. |
| Q9P260 | RELCH | S51 | ochoa | RAB11-binding protein RELCH (LisH domain and HEAT repeat-containing protein KIAA1468) (RAB11 binding and LisH domain, coiled-coil and HEAT repeat-containing) (RAB11-binding protein containing LisH, coiled-coil, and HEAT repeats) | Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP (PubMed:29514919). Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes (PubMed:29514919). {ECO:0000269|PubMed:29514919}. |
| Q9P266 | JCAD | S1307 | ochoa | Junctional cadherin 5-associated protein (Junctional protein associated with coronary artery disease) (JCAD) | None |
| Q9P270 | SLAIN2 | S43 | ochoa | SLAIN motif-containing protein 2 | Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Promotes cytoplasmic microtubule nucleation and elongation. Required for normal structure of the microtubule cytoskeleton during interphase. {ECO:0000269|PubMed:21646404}. |
| Q9P2K8 | EIF2AK4 | S230 | ochoa|psp | eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}. |
| Q9P2Q2 | FRMD4A | S651 | ochoa | FERM domain-containing protein 4A | Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (By similarity). Plays a redundant role with FRMD4B in epithelial polarization (By similarity). May regulate MAPT secretion by activating ARF6-signaling (PubMed:27044754). {ECO:0000250|UniProtKB:Q8BIE6, ECO:0000269|PubMed:27044754}. |
| Q9P2Q2 | FRMD4A | S727 | ochoa | FERM domain-containing protein 4A | Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (By similarity). Plays a redundant role with FRMD4B in epithelial polarization (By similarity). May regulate MAPT secretion by activating ARF6-signaling (PubMed:27044754). {ECO:0000250|UniProtKB:Q8BIE6, ECO:0000269|PubMed:27044754}. |
| Q9P2Q2 | FRMD4A | S795 | ochoa | FERM domain-containing protein 4A | Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (By similarity). Plays a redundant role with FRMD4B in epithelial polarization (By similarity). May regulate MAPT secretion by activating ARF6-signaling (PubMed:27044754). {ECO:0000250|UniProtKB:Q8BIE6, ECO:0000269|PubMed:27044754}. |
| Q9UBC2 | EPS15L1 | S732 | ochoa | Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) | Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}. |
| Q9UBC2 | EPS15L1 | S734 | ochoa | Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) | Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}. |
| Q9UBE0 | SAE1 | S86 | ochoa | SUMO-activating enzyme subunit 1 (Ubiquitin-like 1-activating enzyme E1A) [Cleaved into: SUMO-activating enzyme subunit 1, N-terminally processed] | The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2. {ECO:0000269|PubMed:10187858, ECO:0000269|PubMed:10217437, ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:11481243, ECO:0000269|PubMed:15660128, ECO:0000269|PubMed:20164921, ECO:0000269|PubMed:9920803}. |
| Q9UBP9 | GULP1 | S206 | ochoa | PTB domain-containing engulfment adapter protein 1 (Cell death protein 6 homolog) (PTB domain adapter protein CED-6) (Protein GULP) | May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. Modulates cellular glycosphingolipid and cholesterol transport. May play a role in the internalization and endosomal trafficking of various LRP1 ligands, such as PSAP. Increases cellular levels of GTP-bound ARF6. {ECO:0000269|PubMed:10574763, ECO:0000269|PubMed:10574771, ECO:0000269|PubMed:16497666, ECO:0000269|PubMed:17398097}. |
| Q9UBR4 | LHX3 | S238 | psp | LIM/homeobox protein Lhx3 (LIM homeobox protein 3) | Transcription factor. Recognizes and binds to the consensus sequence motif 5'-AATTAATTA-3' in the regulatory elements of target genes, such as glycoprotein hormones alpha chain CGA and visual system homeobox CHX10, positively modulating transcription; transcription can be co-activated by LDB2. Synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (By similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system (PubMed:21149718). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1 (By similarity). {ECO:0000250|UniProtKB:P50481, ECO:0000269|PubMed:21149718}. |
| Q9UBS3 | DNAJB9 | S103 | ochoa | DnaJ homolog subfamily B member 9 (Endoplasmic reticulum DNA J domain-containing protein 4) (ER-resident protein ERdj4) (ERdj4) (Microvascular endothelial differentiation gene 1 protein) (Mdg-1) | Co-chaperone for Hsp70 protein HSPA5/BiP that acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). J domain-containing co-chaperones stimulate the ATPase activity of Hsp70 proteins and are required for efficient substrate recognition by Hsp70 proteins (PubMed:18400946). In the unstressed endoplasmic reticulum, interacts with the luminal region of ERN1/IRE1 and selectively recruits HSPA5/BiP: HSPA5/BiP disrupts the dimerization of the active ERN1/IRE1 luminal region, thereby inactivating ERN1/IRE1 (By similarity). Also involved in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. Required for survival of B-cell progenitors and normal antibody production (By similarity). {ECO:0000250|UniProtKB:G3H0N9, ECO:0000250|UniProtKB:Q9QYI6, ECO:0000269|PubMed:18400946}. |
| Q9UBS3 | DNAJB9 | S105 | ochoa | DnaJ homolog subfamily B member 9 (Endoplasmic reticulum DNA J domain-containing protein 4) (ER-resident protein ERdj4) (ERdj4) (Microvascular endothelial differentiation gene 1 protein) (Mdg-1) | Co-chaperone for Hsp70 protein HSPA5/BiP that acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). J domain-containing co-chaperones stimulate the ATPase activity of Hsp70 proteins and are required for efficient substrate recognition by Hsp70 proteins (PubMed:18400946). In the unstressed endoplasmic reticulum, interacts with the luminal region of ERN1/IRE1 and selectively recruits HSPA5/BiP: HSPA5/BiP disrupts the dimerization of the active ERN1/IRE1 luminal region, thereby inactivating ERN1/IRE1 (By similarity). Also involved in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. Required for survival of B-cell progenitors and normal antibody production (By similarity). {ECO:0000250|UniProtKB:G3H0N9, ECO:0000250|UniProtKB:Q9QYI6, ECO:0000269|PubMed:18400946}. |
| Q9UBU6 | FAM8A1 | S83 | ochoa | Protein FAM8A1 (Autosomal highly conserved protein) | Plays a role in the assembly of the HRD1 complex, a complex involved in the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD). {ECO:0000269|PubMed:28827405}. |
| Q9UBU7 | DBF4 | S502 | psp | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UBW7 | ZMYM2 | S833 | ochoa | Zinc finger MYM-type protein 2 (Fused in myeloproliferative disorders protein) (Rearranged in atypical myeloproliferative disorder protein) (Zinc finger protein 198) | Involved in the negative regulation of transcription. {ECO:0000269|PubMed:32891193}. |
| Q9UEE9 | CFDP1 | S216 | ochoa | Craniofacial development protein 1 (Bucentaur) | May play a role during embryogenesis. {ECO:0000250}. |
| Q9UER7 | DAXX | S641 | ochoa | Death domain-associated protein 6 (Daxx) (hDaxx) (ETS1-associated protein 1) (EAP1) (Fas death domain-associated protein) | Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as a histone chaperone that facilitates deposition of histone H3.3. Acts as a targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upon neuronal activation associates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV). Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (PubMed:15016915). {ECO:0000269|PubMed:12140263, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:17942542, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:24530302}. |
| Q9UET6 | FTSJ1 | S258 | ochoa | tRNA (cytidine(32)/guanosine(34)-2'-O)-methyltransferase (EC 2.1.1.205) (2'-O-ribose RNA methyltransferase TRM7 homolog) (Protein ftsJ homolog 1) | Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs (PubMed:25404562, PubMed:26310293, PubMed:32198346, PubMed:32558197, PubMed:33771871, PubMed:36720500). Requisite for faithful cytoplasmic translation (PubMed:32393790). Requires THADA for methylation of the nucleotide at position 32 of the anticodon loop of substrate tRNAs (PubMed:25404562, PubMed:26310293). Requires WDR6 for methylation of the nucleotide at position 34 of the anticodon loop of substrate tRNAs (PubMed:32558197, PubMed:33771871). Promotes translation efficiency of the UUU codon (PubMed:32558197). Plays a role in neurogenesis (PubMed:36720500). Required for expression of genes involved in neurogenesis, mitochondrial translation and energy generation, and lipid biosynthesis (PubMed:33771871, PubMed:36720500). Requisite for RNA-mediated gene silencing (PubMed:36720500). May modify position 32 in tRNA(Arg(ACG)), tRNA(Arg(CCG)), tRNA(Arg(UCG)), tRNA(Cys(GCA)), tRNA(Cys(ACA)), tRNA(Gln(CUG)), tRNA(Gln(UUG)), tRNA(Gly(CCC)), tRNA(Leu(CAG))/tRNA(Leu(CAA)), tRNA(Leu(A/IAG)), tRNA(Leu(UAG)), tRNA(Phe(GAA)), tRNA(Pro(AGG))/tRNA(Pro(CGG))/tRNA(Pro(UGG)) and tRNA(Trp(CCA)), and position 34 in tRNA(Phe(GAA)), tRNA(Leu(CAA)), tRNA(Sec(UCA)), and tRNA(Trp(CCA)) (PubMed:26310293, PubMed:32198346, PubMed:32558197, PubMed:33771871, PubMed:36720500). {ECO:0000269|PubMed:25404562, ECO:0000269|PubMed:26310293, ECO:0000269|PubMed:32198346, ECO:0000269|PubMed:32393790, ECO:0000269|PubMed:32558197, ECO:0000269|PubMed:33771871, ECO:0000269|PubMed:36720500}. |
| Q9UEW8 | STK39 | S370 | ochoa | STE20/SPS1-related proline-alanine-rich protein kinase (Ste-20-related kinase) (EC 2.7.11.1) (DCHT) (Serine/threonine-protein kinase 39) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:21321328). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:12740379, PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities (By similarity). Phosphorylates RELT (By similarity). {ECO:0000250|UniProtKB:Q9Z1W9, ECO:0000269|PubMed:12740379, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:34289367}. |
| Q9UGP4 | LIMD1 | S145 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UGP4 | LIMD1 | S360 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UGP4 | LIMD1 | S416 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UH99 | SUN2 | S30 | ochoa | SUN domain-containing protein 2 (Protein unc-84 homolog B) (Rab5-interacting protein) (Rab5IP) (Sad1/unc-84 protein-like 2) | As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5. {ECO:0000250|UniProtKB:Q8BJS4, ECO:0000269|PubMed:18396275, ECO:0000305}. |
| Q9UH99 | SUN2 | S130 | ochoa | SUN domain-containing protein 2 (Protein unc-84 homolog B) (Rab5-interacting protein) (Rab5IP) (Sad1/unc-84 protein-like 2) | As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5. {ECO:0000250|UniProtKB:Q8BJS4, ECO:0000269|PubMed:18396275, ECO:0000305}. |
| Q9UHB7 | AFF4 | S409 | ochoa | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UHF7 | TRPS1 | S1061 | ochoa | Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) | Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}. |
| Q9UHI5 | SLC7A8 | S29 | ochoa | Large neutral amino acids transporter small subunit 2 (L-type amino acid transporter 2) (hLAT2) (Solute carrier family 7 member 8) | Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1. Functions as amino acid antiporter mediating the influx of extracellular essential amino acids mainly in exchange with the efflux of highly concentrated intracellular amino acids (PubMed:10391915, PubMed:11311135, PubMed:11847106, PubMed:12716892, PubMed:15081149, PubMed:15918515, PubMed:29355479, PubMed:33298890, PubMed:34848541). Has relatively symmetrical selectivities but strongly asymmetrical substrate affinities at both the intracellular and extracellular sides of the transporter (PubMed:11847106). This asymmetry allows SLC7A8 to regulate intracellular amino acid pools (mM concentrations) by exchange with external amino acids (uM concentration range), equilibrating the relative concentrations of different amino acids across the plasma membrane instead of mediating their net uptake (PubMed:10391915, PubMed:11847106). May play an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney (PubMed:12716892). Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity (PubMed:12117417). Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane (PubMed:15769744). Imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4) (By similarity). Mediates the uptake of L-DOPA (By similarity). May participate in auditory function (By similarity). {ECO:0000250|UniProtKB:Q9QXW9, ECO:0000250|UniProtKB:Q9WVR6, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11847106, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15081149, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15918515, ECO:0000269|PubMed:29355479, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:34848541}. |
| Q9UHK0 | NUFIP1 | S314 | ochoa | FMR1-interacting protein NUFIP1 (Nuclear FMR1-interacting protein 1) (Nuclear FMRP-interacting protein 1) | Binds RNA. {ECO:0000269|PubMed:10556305}. |
| Q9UIG0 | BAZ1B | S708 | ochoa | Tyrosine-protein kinase BAZ1B (EC 2.7.10.2) (Bromodomain adjacent to zinc finger domain protein 1B) (Williams syndrome transcription factor) (Williams-Beuren syndrome chromosomal region 10 protein) (Williams-Beuren syndrome chromosomal region 9 protein) (hWALp2) | Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802, PubMed:19234442). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802, PubMed:19234442). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (PubMed:28801535). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (PubMed:15543136). {ECO:0000250|UniProtKB:Q9Z277, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:28801535}. |
| Q9UIQ6 | LNPEP | S51 | ochoa | Leucyl-cystinyl aminopeptidase (Cystinyl aminopeptidase) (EC 3.4.11.3) (Insulin-regulated membrane aminopeptidase) (Insulin-responsive aminopeptidase) (IRAP) (Oxytocinase) (OTase) (Placental leucine aminopeptidase) (P-LAP) [Cleaved into: Leucyl-cystinyl aminopeptidase, pregnancy serum form] | Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. {ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:11707427, ECO:0000269|PubMed:1731608}. |
| Q9UJC3 | HOOK1 | S235 | ochoa | Protein Hook homolog 1 (h-hook1) (hHK1) | Component of the FTS/Hook/FHIP complex (FHF complex) (PubMed:18799622, PubMed:32073997). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex) (PubMed:18799622). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). Required for spermatid differentiation. Probably involved in the positioning of the microtubules of the manchette and the flagellum in relation to the membrane skeleton (By similarity). {ECO:0000250|UniProtKB:Q8BIL5, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}. |
| Q9UJF2 | RASAL2 | S641 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UJV9 | DDX41 | S68 | ochoa | Probable ATP-dependent RNA helicase DDX41 (EC 3.6.4.13) (DEAD box protein 41) (DEAD box protein abstrakt homolog) | Multifunctional protein that participates in many aspects of cellular RNA metabolism. Plays pivotal roles in innate immune sensing and hematopoietic homeostasis (PubMed:34473945). Recognizes foreign or self-nucleic acids generated during microbial infection, thereby initiating anti-pathogen responses (PubMed:23222971). Mechanistically, phosphorylation by BTK allows binding to dsDNA leading to interaction with STING1 (PubMed:25704810). Modulates the homeostasis of dsDNA through its ATP-dependent DNA-unwinding activity and ATP-independent strand-annealing activity (PubMed:35613581). In turn, induces STING1-mediated type I interferon and cytokine responses to DNA and DNA viruses (PubMed:35613581). Selectively modulates the transcription of certain immunity-associated genes by regulating their alternative splicing (PubMed:33650667). Binds to RNA (R)-loops, structures consisting of DNA/RNA hybrids and a displaced strand of DNA that occur during transcription, and prevents their accumulation, thereby maintaining genome stability (PubMed:36229594). Also participates in pre-mRNA splicing, translational regulation and snoRNA processing, which is essential for ribosome biogenesis (PubMed:36229594, PubMed:36780110). {ECO:0000250|UniProtKB:Q91VN6, ECO:0000269|PubMed:23222971, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:25920683, ECO:0000269|PubMed:33650667, ECO:0000269|PubMed:34473945, ECO:0000269|PubMed:35613581, ECO:0000269|PubMed:36229594, ECO:0000269|PubMed:36780110}. |
| Q9UK76 | JPT1 | S115 | ochoa | Jupiter microtubule associated homolog 1 (Androgen-regulated protein 2) (Hematological and neurological expressed 1 protein) [Cleaved into: Jupiter microtubule associated homolog 1, N-terminally processed] | Modulates negatively AKT-mediated GSK3B signaling (PubMed:21323578, PubMed:22155408). Induces CTNNB1 'Ser-33' phosphorylation and degradation through the suppression of the inhibitory 'Ser-9' phosphorylation of GSK3B, which represses the function of the APC:CTNNB1:GSK3B complex and the interaction with CDH1/E-cadherin in adherent junctions (PubMed:25169422). Plays a role in the regulation of cell cycle and cell adhesion (PubMed:25169422, PubMed:25450365). Has an inhibitory role on AR-signaling pathway through the induction of receptor proteasomal degradation (PubMed:22155408). {ECO:0000269|PubMed:21323578, ECO:0000269|PubMed:22155408, ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:25450365}. |
| Q9UK96 | FBXO10 | S342 | ochoa | F-box only protein 10 | Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Mediates the ubiquitination and degradation of BCL2, an antiapoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. Targets also the receptor for advanced glycation end products RAGE for ubiquitination and subsequent lysosomal degradation (PubMed:28515150). Directly controls HGAL/GCSAM ubiquitination and degradation and thereby decreases BCR signaling (PubMed:31570756). {ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:28515150, ECO:0000269|PubMed:31570756}. |
| Q9UKE5 | TNIK | S701 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
| Q9UKF6 | CPSF3 | S659 | ochoa | Cleavage and polyadenylation specificity factor subunit 3 (EC 3.1.27.-) (Cleavage and polyadenylation specificity factor 73 kDa subunit) (CPSF 73 kDa subunit) (mRNA 3'-end-processing endonuclease CPSF-73) | Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as an mRNA 3'-end-processing endonuclease (PubMed:30507380). Also involved in the histone 3'-end pre-mRNA processing (PubMed:30507380). U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner. Required for entering/progressing through S-phase of the cell cycle (PubMed:30507380). Required for the selective processing of microRNAs (miRNAs) during embryonic stem cell differentiation via its interaction with ISY1 (By similarity). Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (By similarity). Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (By similarity). {ECO:0000250|UniProtKB:Q9QXK7, ECO:0000269|PubMed:14749727, ECO:0000269|PubMed:15037765, ECO:0000269|PubMed:17128255, ECO:0000269|PubMed:18688255, ECO:0000269|PubMed:30507380}. |
| Q9UKJ3 | GPATCH8 | S352 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKJ3 | GPATCH8 | S765 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKJ3 | GPATCH8 | S1076 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKK3 | PARP4 | S1507 | ochoa | Protein mono-ADP-ribosyltransferase PARP4 (EC 2.4.2.-) (193 kDa vault protein) (ADP-ribosyltransferase diphtheria toxin-like 4) (ARTD4) (PARP-related/IalphaI-related H5/proline-rich) (PH5P) (Poly [ADP-ribose] polymerase 4) (PARP-4) (Vault poly(ADP-ribose) polymerase) (VPARP) | Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. {ECO:0000269|PubMed:25043379}. |
| Q9UKX7 | NUP50 | S227 | ochoa | Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) | Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}. |
| Q9ULC3 | RAB23 | S200 | ochoa | Ras-related protein Rab-23 (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Together with SUFU, prevents nuclear import of GLI1, and thereby inhibits GLI1 transcription factor activity. Regulates GLI1 in differentiating chondrocytes. Likewise, regulates GLI3 proteolytic processing and modulates GLI2 and GLI3 transcription factor activity. Plays a role in autophagic vacuole assembly, and mediates defense against pathogens, such as S.aureus, by promoting their capture by autophagosomes that then merge with lysosomes. {ECO:0000269|PubMed:22365972, ECO:0000269|PubMed:22452336}. |
| Q9ULC8 | ZDHHC8 | S606 | ochoa | Palmitoyltransferase ZDHHC8 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 8) (DHHC-8) (Zinc finger protein 378) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes (Probable). Through the palmitoylation of ABCA1 regulates the localization of the transporter to the plasma membrane and thereby regulates its function in cholesterol and phospholipid efflux (Probable). Could also pamitoylate the D(2) dopamine receptor DRD2 and regulate its stability and localization to the plasma membrane (Probable). Could also play a role in glutamatergic transmission (By similarity). {ECO:0000250|UniProtKB:Q5Y5T5, ECO:0000305|PubMed:19556522, ECO:0000305|PubMed:23034182, ECO:0000305|PubMed:26535572}.; FUNCTION: (Microbial infection) Able to palmitoylate SARS coronavirus-2/SARS-CoV-2 spike protein following its synthesis in the endoplasmic reticulum (ER). In the infected cell, promotes spike biogenesis by protecting it from premature ER degradation, increases half-life and controls the lipid organization of its immediate membrane environment. Once the virus has formed, spike palmitoylation controls fusion with the target cell. {ECO:0000269|PubMed:34599882}. |
| Q9ULE3 | DENND2A | S257 | ochoa | DENN domain-containing protein 2A | Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. May play a role in late endosomes back to trans-Golgi network/TGN transport. {ECO:0000269|PubMed:20937701}. |
| Q9ULE6 | PALD1 | S483 | ochoa | Paladin | None |
| Q9ULI0 | ATAD2B | S61 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9ULJ3 | ZBTB21 | S322 | ochoa | Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) | Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}. |
| Q9ULT0 | TTC7A | S51 | ochoa | Tetratricopeptide repeat protein 7A (TPR repeat protein 7A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}. |
| Q9ULT0 | TTC7A | S674 | ochoa | Tetratricopeptide repeat protein 7A (TPR repeat protein 7A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}. |
| Q9ULU4 | ZMYND8 | S1141 | ochoa | MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) | Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}. |
| Q9ULW3 | ABT1 | S208 | ochoa | Activator of basal transcription 1 (hABT1) (Basal transcriptional activator) | Could be a novel TATA-binding protein (TBP) which can function as a basal transcription activator. Can act as a regulator of basal transcription for class II genes (By similarity). {ECO:0000250}. |
| Q9ULX6 | AKAP8L | S117 | ochoa | A-kinase anchor protein 8-like (AKAP8-like protein) (Helicase A-binding protein 95) (HAP95) (Homologous to AKAP95 protein) (HA95) (Neighbor of A-kinase-anchoring protein 95) (Neighbor of AKAP95) | Could play a role in constitutive transport element (CTE)-mediated gene expression by association with DHX9. Increases CTE-dependent nuclear unspliced mRNA export (PubMed:10748171, PubMed:11402034). Proposed to target PRKACA to the nucleus but does not seem to be implicated in the binding of regulatory subunit II of PKA (PubMed:10761695, PubMed:11884601). May be involved in nuclear envelope breakdown and chromatin condensation. May be involved in anchoring nuclear membranes to chromatin in interphase and in releasing membranes from chromating at mitosis (PubMed:11034899). May regulate the initiation phase of DNA replication when associated with TMPO isoform Beta (PubMed:12538639). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function seems to act redundantly with AKAP8 (PubMed:16980585). May be involved in regulation of pre-mRNA splicing (PubMed:17594903). {ECO:0000269|PubMed:10748171, ECO:0000269|PubMed:11034899, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11884601, ECO:0000269|PubMed:12538639, ECO:0000269|PubMed:16980585, ECO:0000305|PubMed:10761695}.; FUNCTION: (Microbial infection) In case of EBV infection, may target PRKACA to EBNA-LP-containing nuclear sites to modulate transcription from specific promoters. {ECO:0000269|PubMed:11884601}.; FUNCTION: (Microbial infection) Can synergize with DHX9 to activate the CTE-mediated gene expression of type D retroviruses. {ECO:0000269|PubMed:11402034}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, involved in the DHX9-promoted annealing of host tRNA(Lys3) to viral genomic RNA as a primer in reverse transcription; in vitro negatively regulates DHX9 annealing activity. {ECO:0000269|PubMed:25034436}. |
| Q9ULX9 | MAFF | S146 | ochoa | Transcription factor MafF (U-Maf) (V-maf musculoaponeurotic fibrosarcoma oncogene homolog F) | Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (PubMed:8932385). However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2L1/NRF1, and recruiting them to specific DNA-binding sites. Interacts with the upstream promoter region of the oxytocin receptor gene (PubMed:16549056, PubMed:8932385). May be a transcriptional enhancer in the up-regulation of the oxytocin receptor gene at parturition (PubMed:10527846). {ECO:0000269|PubMed:10527846, ECO:0000269|PubMed:16549056, ECO:0000269|PubMed:8932385}. |
| Q9UMD9 | COL17A1 | S61 | ochoa | Collagen alpha-1(XVII) chain (180 kDa bullous pemphigoid antigen 2) (Bullous pemphigoid antigen 2) [Cleaved into: 120 kDa linear IgA disease antigen (120 kDa linear IgA dermatosis antigen) (Linear IgA disease antigen 1) (LAD-1); 97 kDa linear IgA disease antigen (97 kDa linear IgA bullous dermatosis antigen) (97 kDa LAD antigen) (97-LAD) (Linear IgA bullous disease antigen of 97 kDa) (LABD97)] | May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.; FUNCTION: The 120 kDa linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion. Is the target of linear IgA bullous dermatosis autoantibodies. |
| Q9UMD9 | COL17A1 | S112 | ochoa | Collagen alpha-1(XVII) chain (180 kDa bullous pemphigoid antigen 2) (Bullous pemphigoid antigen 2) [Cleaved into: 120 kDa linear IgA disease antigen (120 kDa linear IgA dermatosis antigen) (Linear IgA disease antigen 1) (LAD-1); 97 kDa linear IgA disease antigen (97 kDa linear IgA bullous dermatosis antigen) (97 kDa LAD antigen) (97-LAD) (Linear IgA bullous disease antigen of 97 kDa) (LABD97)] | May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.; FUNCTION: The 120 kDa linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion. Is the target of linear IgA bullous dermatosis autoantibodies. |
| Q9UMN6 | KMT2B | S346 | ochoa | Histone-lysine N-methyltransferase 2B (Lysine N-methyltransferase 2B) (EC 2.1.1.364) (Myeloid/lymphoid or mixed-lineage leukemia protein 4) (Trithorax homolog 2) (WW domain-binding protein 7) (WBP-7) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17707229, PubMed:25561738). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (PubMed:24081332). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250|UniProtKB:O08550, ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q9UMN6 | KMT2B | S941 | ochoa | Histone-lysine N-methyltransferase 2B (Lysine N-methyltransferase 2B) (EC 2.1.1.364) (Myeloid/lymphoid or mixed-lineage leukemia protein 4) (Trithorax homolog 2) (WW domain-binding protein 7) (WBP-7) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17707229, PubMed:25561738). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (PubMed:24081332). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250|UniProtKB:O08550, ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q9UMN6 | KMT2B | S2146 | ochoa | Histone-lysine N-methyltransferase 2B (Lysine N-methyltransferase 2B) (EC 2.1.1.364) (Myeloid/lymphoid or mixed-lineage leukemia protein 4) (Trithorax homolog 2) (WW domain-binding protein 7) (WBP-7) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17707229, PubMed:25561738). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (PubMed:24081332). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250|UniProtKB:O08550, ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q9UMS6 | SYNPO2 | S595 | ochoa | Synaptopodin-2 (Genethonin-2) (Myopodin) | Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}. |
| Q9UMZ2 | SYNRG | S821 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UMZ2 | SYNRG | S935 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UN19 | DAPP1 | S117 | ochoa | Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide (hDAPP1) (B lymphocyte adapter protein Bam32) (B-cell adapter molecule of 32 kDa) | May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K. {ECO:0000269|PubMed:10770799}. |
| Q9UNF1 | MAGED2 | S190 | ochoa | Melanoma-associated antigen D2 (11B6) (Breast cancer-associated gene 1 protein) (BCG-1) (Hepatocellular carcinoma-associated protein JCL-1) (MAGE-D2 antigen) | Regulates the expression, localization to the plasma membrane and function of the sodium chloride cotransporters SLC12A1 and SLC12A3, two key components of salt reabsorption in the distal renal tubule. {ECO:0000269|PubMed:27120771}. |
| Q9UNI6 | DUSP12 | S241 | ochoa | Dual specificity protein phosphatase 12 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity tyrosine phosphatase YVH1) | Dual specificity phosphatase; can dephosphorylate both phosphotyrosine and phosphoserine or phosphothreonine residues. Can dephosphorylate glucokinase (in vitro) (By similarity). Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate and other in vitro substrates (PubMed:10446167, PubMed:24531476). {ECO:0000250|UniProtKB:Q9JIM4, ECO:0000269|PubMed:10446167, ECO:0000269|PubMed:24531476}. |
| Q9UNZ2 | NSFL1C | S262 | ochoa | NSFL1 cofactor p47 (UBX domain-containing protein 2C) (p97 cofactor p47) | Reduces the ATPase activity of VCP (By similarity). Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Inhibits the activity of CTSL (in vitro) (PubMed:15498563). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase (PubMed:23649807). Also, regulates spindle orientation during mitosis (PubMed:23649807). {ECO:0000250|UniProtKB:O35987, ECO:0000269|PubMed:15498563, ECO:0000269|PubMed:23649807}. |
| Q9UP83 | COG5 | S49 | ochoa | Conserved oligomeric Golgi complex subunit 5 (COG complex subunit 5) (13S Golgi transport complex 90 kDa subunit) (GTC-90) (Component of oligomeric Golgi complex 5) (Golgi transport complex 1) | Required for normal Golgi function. {ECO:0000250|UniProtKB:Q9VJD3}. |
| Q9UP83 | COG5 | S197 | ochoa | Conserved oligomeric Golgi complex subunit 5 (COG complex subunit 5) (13S Golgi transport complex 90 kDa subunit) (GTC-90) (Component of oligomeric Golgi complex 5) (Golgi transport complex 1) | Required for normal Golgi function. {ECO:0000250|UniProtKB:Q9VJD3}. |
| Q9UPP1 | PHF8 | S1024 | ochoa | Histone lysine demethylase PHF8 (EC 1.14.11.27) (EC 1.14.11.65) (PHD finger protein 8) ([histone H3]-dimethyl-L-lysine(36) demethylase PHF8) ([histone H3]-dimethyl-L-lysine(9) demethylase PHF8) | Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}. |
| Q9UPQ9 | TNRC6B | S1432 | ochoa | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}. |
| Q9UPT8 | ZC3H4 | S815 | ochoa | Zinc finger CCCH domain-containing protein 4 | RNA-binding protein that suppresses transcription of long non-coding RNAs (lncRNAs) (PubMed:33767452, PubMed:33913806). LncRNAs are defined as transcripts more than 200 nucleotides that are not translated into protein (PubMed:33767452, PubMed:33913806). Together with WDR82, part of a transcription termination checkpoint that promotes transcription termination of lncRNAs and their subsequent degradation by the exosome (PubMed:33767452, PubMed:33913806). The transcription termination checkpoint is activated by the inefficiently spliced first exon of lncRNAs (PubMed:33767452). {ECO:0000269|PubMed:33767452, ECO:0000269|PubMed:33913806}. |
| Q9UPU5 | USP24 | S1616 | ochoa|psp | Ubiquitin carboxyl-terminal hydrolase 24 (EC 3.4.19.12) (Deubiquitinating enzyme 24) (Ubiquitin thioesterase 24) (Ubiquitin-specific-processing protease 24) | Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}. |
| Q9UPU5 | USP24 | S1854 | ochoa | Ubiquitin carboxyl-terminal hydrolase 24 (EC 3.4.19.12) (Deubiquitinating enzyme 24) (Ubiquitin thioesterase 24) (Ubiquitin-specific-processing protease 24) | Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}. |
| Q9UPV9 | TRAK1 | S537 | ochoa | Trafficking kinesin-binding protein 1 (106 kDa O-GlcNAc transferase-interacting protein) (Protein Milton) | Involved in the regulation of endosome-to-lysosome trafficking, including endocytic trafficking of EGF-EGFR complexes and GABA-A receptors (PubMed:18675823). Involved in mitochondrial motility. When O-glycosylated, abolishes mitochondrial motility. Crucial for recruiting OGT to the mitochondrial surface of neuronal processes (PubMed:24995978). TRAK1 and RHOT form an essential protein complex that links KIF5 to mitochondria for light chain-independent, anterograde transport of mitochondria (By similarity). {ECO:0000250|UniProtKB:Q960V3, ECO:0000269|PubMed:18675823, ECO:0000269|PubMed:24995978}. |
| Q9UPZ3 | HPS5 | S1052 | ochoa | BLOC-2 complex member HPS5 (Alpha-integrin-binding protein 63) (Hermansky-Pudlak syndrome 5 protein) (Ruby-eye protein 2 homolog) (Ru2) | May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules. Regulates intracellular vesicular trafficking in fibroblasts. May be involved in the regulation of general functions of integrins. {ECO:0000269|PubMed:15296495, ECO:0000269|PubMed:17301833}. |
| Q9UQ35 | SRRM2 | S449 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQ35 | SRRM2 | S1032 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQ35 | SRRM2 | S2141 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQ35 | SRRM2 | S2155 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQC2 | GAB2 | S285 | ochoa | GRB2-associated-binding protein 2 (GRB2-associated binder 2) (Growth factor receptor bound protein 2-associated protein 2) (pp100) | Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis. {ECO:0000269|PubMed:15750601, ECO:0000269|PubMed:19172738}. |
| Q9UQE7 | SMC3 | S383 | psp | Structural maintenance of chromosomes protein 3 (SMC protein 3) (SMC-3) (Basement membrane-associated chondroitin proteoglycan) (Bamacan) (Chondroitin sulfate proteoglycan 6) (Chromosome-associated polypeptide) (hCAP) | Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement. {ECO:0000269|PubMed:11076961, ECO:0000269|PubMed:19907496}. |
| Q9UQE7 | SMC3 | S1074 | ochoa | Structural maintenance of chromosomes protein 3 (SMC protein 3) (SMC-3) (Basement membrane-associated chondroitin proteoglycan) (Bamacan) (Chondroitin sulfate proteoglycan 6) (Chromosome-associated polypeptide) (hCAP) | Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement. {ECO:0000269|PubMed:11076961, ECO:0000269|PubMed:19907496}. |
| Q9Y272 | RASD1 | S232 | ochoa | Dexamethasone-induced Ras-related protein 1 (Activator of G-protein signaling 1) | Small GTPase. Negatively regulates the transcription regulation activity of the APBB1/FE65-APP complex via its interaction with APBB1/FE65 (By similarity). {ECO:0000250}. |
| Q9Y283 | INVS | S661 | ochoa | Inversin (Inversion of embryo turning homolog) (Nephrocystin-2) | Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:15852005, ECO:0000269|PubMed:18371931}. |
| Q9Y2H5 | PLEKHA6 | S282 | ochoa | Pleckstrin homology domain-containing family A member 6 (PH domain-containing family A member 6) (Phosphoinositol 3-phosphate-binding protein 3) (PEPP-3) | None |
| Q9Y2I1 | NISCH | S1022 | ochoa | Nischarin (Imidazoline receptor 1) (I-1) (IR1) (Imidazoline receptor antisera-selected protein) (hIRAS) (Imidazoline-1 receptor) (I1R) (Imidazoline-1 receptor candidate protein) (I-1 receptor candidate protein) (I1R candidate protein) | Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Also inhibits LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures. {ECO:0000250, ECO:0000269|PubMed:10882231, ECO:0000269|PubMed:12868002, ECO:0000269|PubMed:15028619, ECO:0000269|PubMed:15028621, ECO:0000269|PubMed:15475348}. |
| Q9Y2J4 | AMOTL2 | S534 | ochoa | Angiomotin-like protein 2 (Leman coiled-coil protein) (LCCP) | Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments. Plays a role in coupling actin fibers to cell junctions in endothelial cells and is therefore required for correct endothelial cell morphology via facilitating transcellular transmission of mechanical force resulting in endothelial cell elongation (By similarity). Required for the anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane which facilitates organization of radial actin fiber structure and cellular response to contractile forces (PubMed:28842668). This contributes to maintenance of cell area, size, shape, epithelial sheet organization and trophectoderm cell properties that facilitate blastocyst zona hatching (PubMed:28842668). Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. Activates the Hippo signaling pathway in response to cell contact inhibition via interaction with and ubiquitination by Crumbs complex-bound WWP1 (PubMed:34404733). Ubiquitinated AMOTL2 then interacts with LATS2 which in turn phosphorylates YAP1, excluding it from the nucleus and localizing it to the cytoplasm and tight junctions, therefore ultimately repressing YAP1-driven transcription of target genes (PubMed:17293535, PubMed:21205866, PubMed:26598551). Acts to inhibit WWTR1/TAZ transcriptional coactivator activity via sequestering WWTR1/TAZ in the cytoplasm and at tight junctions (PubMed:23911299). Regulates the size and protein composition of the podosome cortex and core at myofibril neuromuscular junctions (PubMed:23525008). Selectively promotes FGF-induced MAPK activation through SRC (PubMed:17293535). May play a role in the polarity, proliferation and migration of endothelial cells. {ECO:0000250|UniProtKB:Q8K371, ECO:0000269|PubMed:17293535, ECO:0000269|PubMed:21205866, ECO:0000269|PubMed:21937427, ECO:0000269|PubMed:22362771, ECO:0000269|PubMed:23525008, ECO:0000269|PubMed:23911299, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:28842668, ECO:0000269|PubMed:34404733}. |
| Q9Y2J4 | AMOTL2 | S537 | ochoa | Angiomotin-like protein 2 (Leman coiled-coil protein) (LCCP) | Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments. Plays a role in coupling actin fibers to cell junctions in endothelial cells and is therefore required for correct endothelial cell morphology via facilitating transcellular transmission of mechanical force resulting in endothelial cell elongation (By similarity). Required for the anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane which facilitates organization of radial actin fiber structure and cellular response to contractile forces (PubMed:28842668). This contributes to maintenance of cell area, size, shape, epithelial sheet organization and trophectoderm cell properties that facilitate blastocyst zona hatching (PubMed:28842668). Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. Activates the Hippo signaling pathway in response to cell contact inhibition via interaction with and ubiquitination by Crumbs complex-bound WWP1 (PubMed:34404733). Ubiquitinated AMOTL2 then interacts with LATS2 which in turn phosphorylates YAP1, excluding it from the nucleus and localizing it to the cytoplasm and tight junctions, therefore ultimately repressing YAP1-driven transcription of target genes (PubMed:17293535, PubMed:21205866, PubMed:26598551). Acts to inhibit WWTR1/TAZ transcriptional coactivator activity via sequestering WWTR1/TAZ in the cytoplasm and at tight junctions (PubMed:23911299). Regulates the size and protein composition of the podosome cortex and core at myofibril neuromuscular junctions (PubMed:23525008). Selectively promotes FGF-induced MAPK activation through SRC (PubMed:17293535). May play a role in the polarity, proliferation and migration of endothelial cells. {ECO:0000250|UniProtKB:Q8K371, ECO:0000269|PubMed:17293535, ECO:0000269|PubMed:21205866, ECO:0000269|PubMed:21937427, ECO:0000269|PubMed:22362771, ECO:0000269|PubMed:23525008, ECO:0000269|PubMed:23911299, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:28842668, ECO:0000269|PubMed:34404733}. |
| Q9Y2K7 | KDM2A | S883 | ochoa | Lysine-specific demethylase 2A (EC 1.14.11.27) (CXXC-type zinc finger protein 8) (F-box and leucine-rich repeat protein 11) (F-box protein FBL7) (F-box protein Lilina) (F-box/LRR-repeat protein 11) (JmjC domain-containing histone demethylation protein 1A) ([Histone-H3]-lysine-36 demethylase 1A) | Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-BMAL1 heterodimer and RORA in a catalytically-independent manner (PubMed:26037310). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:19001877, ECO:0000269|PubMed:26037310, ECO:0000269|PubMed:28262558}. |
| Q9Y2W1 | THRAP3 | S232 | ochoa | Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) | Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| Q9Y2X7 | GIT1 | S592 | ochoa | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y2Z0 | SUGT1 | S321 | ochoa|psp | Protein SGT1 homolog (Protein 40-6-3) (Sgt1) (Suppressor of G2 allele of SKP1 homolog) | May play a role in ubiquitination and subsequent proteasomal degradation of target proteins. |
| Q9Y3B2 | EXOSC1 | S21 | ochoa | Exosome complex component CSL4 (Exosome component 1) | Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC1 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC6 and EXOSC8. |
| Q9Y3B2 | EXOSC1 | S24 | ochoa | Exosome complex component CSL4 (Exosome component 1) | Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC1 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC6 and EXOSC8. |
| Q9Y3B9 | RRP15 | S51 | ochoa | RRP15-like protein (Ribosomal RNA-processing protein 15) | None |
| Q9Y3M8 | STARD13 | S171 | ochoa | StAR-related lipid transfer protein 13 (46H23.2) (Deleted in liver cancer 2 protein) (DLC-2) (Rho GTPase-activating protein) (START domain-containing protein 13) (StARD13) | GTPase-activating protein for RhoA, and perhaps for Cdc42. May be involved in regulation of cytoskeletal reorganization, cell proliferation and cell motility. Acts a tumor suppressor in hepatocellular carcinoma cells. {ECO:0000269|PubMed:14697242, ECO:0000269|PubMed:16217026}. |
| Q9Y446 | PKP3 | S141 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y478 | PRKAB1 | S96 | ochoa | 5'-AMP-activated protein kinase subunit beta-1 (AMPK subunit beta-1) (AMPKb) | Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3). |
| Q9Y4B5 | MTCL1 | S790 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4B5 | MTCL1 | S1656 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4B5 | MTCL1 | S1820 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| Q9Y4F9 | RIPOR2 | S588 | ochoa | Rho family-interacting cell polarization regulator 2 | Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization (PubMed:17150207, PubMed:23241886, PubMed:24687993, PubMed:24958875, PubMed:25588844, PubMed:27556504). Inhibits chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration (PubMed:23241886). Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion (By similarity). Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear (By similarity). Plays a role for maintaining the structural organization of the basal domain of stereocilia (By similarity). Involved in mechanosensory hair cell function (By similarity). Required for normal hearing (PubMed:24958875). {ECO:0000250|UniProtKB:Q80U16, ECO:0000269|PubMed:17150207, ECO:0000269|PubMed:23241886, ECO:0000269|PubMed:24687993, ECO:0000269|PubMed:24958875, ECO:0000269|PubMed:27556504}.; FUNCTION: [Isoform 2]: Acts as an inhibitor of the small GTPase RHOA (PubMed:25588844). Plays a role in fetal mononuclear myoblast differentiation by promoting filopodia and myotube formation (PubMed:17150207). Maintains naive T lymphocytes in a quiescent state (PubMed:27556504). {ECO:0000269|PubMed:17150207, ECO:0000269|PubMed:25588844, ECO:0000269|PubMed:27556504}. |
| Q9Y4G6 | TLN2 | S460 | ochoa | Talin-2 | As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion. Recruits PIP5K1C to focal adhesion plaques and strongly activates its kinase activity (By similarity). {ECO:0000250}. |
| Q9Y4G8 | RAPGEF2 | S1248 | psp | Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) | Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}. |
| Q9Y4H2 | IRS2 | S608 | ochoa | Insulin receptor substrate 2 (IRS-2) | Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:25879670). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:24616100). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:15316008, PubMed:19109239). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). Plays a role in cell cycle progression by promoting a robust spindle assembly checkpoint (SAC) during M-phase (PubMed:32554797). In macrophages, IL4-induced tyrosine phosphorylation of IRS2 leads to the recruitment and activation of phosphoinositide 3-kinase (PI3K) (PubMed:19109239). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:15316008, ECO:0000269|PubMed:19109239, ECO:0000269|PubMed:24616100, ECO:0000269|PubMed:25879670, ECO:0000269|PubMed:32554797}. |
| Q9Y4H2 | IRS2 | S667 | psp | Insulin receptor substrate 2 (IRS-2) | Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:25879670). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:24616100). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:15316008, PubMed:19109239). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). Plays a role in cell cycle progression by promoting a robust spindle assembly checkpoint (SAC) during M-phase (PubMed:32554797). In macrophages, IL4-induced tyrosine phosphorylation of IRS2 leads to the recruitment and activation of phosphoinositide 3-kinase (PI3K) (PubMed:19109239). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:15316008, ECO:0000269|PubMed:19109239, ECO:0000269|PubMed:24616100, ECO:0000269|PubMed:25879670, ECO:0000269|PubMed:32554797}. |
| Q9Y4L1 | HYOU1 | S964 | ochoa | Hypoxia up-regulated protein 1 (150 kDa oxygen-regulated protein) (ORP-150) (170 kDa glucose-regulated protein) (GRP-170) (Heat shock protein family H member 4) | Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. Promotes HSPA5/BiP-mediated ATP nucleotide exchange and thereby activates the unfolded protein response (UPR) pathway in the presence of endoplasmic reticulum stress (By similarity). May play a role as a molecular chaperone and participate in protein folding. {ECO:0000250|UniProtKB:Q9JKR6, ECO:0000269|PubMed:10037731}. |
| Q9Y520 | PRRC2C | S653 | ochoa | Protein PRRC2C (BAT2 domain-containing protein 1) (HBV X-transactivated gene 2 protein) (HBV XAg-transactivated protein 2) (HLA-B-associated transcript 2-like 2) (Proline-rich and coiled-coil-containing protein 2C) | Required for efficient formation of stress granules. {ECO:0000269|PubMed:29395067}. |
| Q9Y520 | PRRC2C | S2665 | ochoa | Protein PRRC2C (BAT2 domain-containing protein 1) (HBV X-transactivated gene 2 protein) (HBV XAg-transactivated protein 2) (HLA-B-associated transcript 2-like 2) (Proline-rich and coiled-coil-containing protein 2C) | Required for efficient formation of stress granules. {ECO:0000269|PubMed:29395067}. |
| Q9Y570 | PPME1 | S25 | ochoa | Protein phosphatase methylesterase 1 (PME-1) (EC 3.1.1.89) | Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme. {ECO:0000269|PubMed:10318862}. |
| Q9Y5A9 | YTHDF2 | S359 | ochoa | YTH domain-containing family protein 2 (DF2) (CLL-associated antigen KW-14) (High-glucose-regulated protein 8) (Renal carcinoma antigen NY-REN-2) | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:25412658, PubMed:25412661, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31292544, PubMed:31388144, PubMed:31642031, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440). {ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658, ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30065315, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:30930054, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:31642031, ECO:0000269|PubMed:31815440, ECO:0000269|PubMed:32169943, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282). {ECO:0000269|PubMed:29447282}.; FUNCTION: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}. |
| Q9Y5B0 | CTDP1 | S869 | ochoa | RNA polymerase II subunit A C-terminal domain phosphatase (EC 3.1.3.16) (TFIIF-associating CTD phosphatase) | Processively dephosphorylates 'Ser-2' and 'Ser-5' of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. This promotes the activity of RNA polymerase II. Plays a role in the exit from mitosis by dephosphorylating crucial mitotic substrates (USP44, CDC20 and WEE1) that are required for M-phase-promoting factor (MPF)/CDK1 inactivation. {ECO:0000269|PubMed:22692537}. |
| Q9Y5B6 | PAXBP1 | S295 | ochoa | PAX3- and PAX7-binding protein 1 (GC-rich sequence DNA-binding factor 1) | Adapter protein linking the transcription factors PAX3 and PAX7 to the histone methylation machinery and involved in myogenesis. Associates with a histone methyltransferase complex that specifically mediates dimethylation and trimethylation of 'Lys-4' of histone H3. Mediates the recruitment of that complex to the transcription factors PAX3 and PAX7 on chromatin to regulate the expression of genes involved in muscle progenitor cells proliferation including ID3 and CDC20. {ECO:0000250|UniProtKB:P58501}. |
| Q9Y6A5 | TACC3 | S402 | ochoa | Transforming acidic coiled-coil-containing protein 3 (ERIC-1) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:21297582, PubMed:23532825). May be involved in the control of cell growth and differentiation. May contribute to cancer (PubMed:14767476). {ECO:0000250|UniProtKB:Q9JJ11, ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| Q9Y6A5 | TACC3 | S505 | ochoa | Transforming acidic coiled-coil-containing protein 3 (ERIC-1) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:21297582, PubMed:23532825). May be involved in the control of cell growth and differentiation. May contribute to cancer (PubMed:14767476). {ECO:0000250|UniProtKB:Q9JJ11, ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| Q9Y6B6 | SAR1B | S162 | ochoa | Small COPII coat GTPase SAR1B (EC 3.6.5.2) (GTP-binding protein B) (GTBPB) (Secretion-associated Ras-related GTPase 1B) | Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport. The active GTP-bound form inserts into the endoplasmic reticulum membrane where it recruits the remainder of the coat protein complex II/COPII (PubMed:23433038, PubMed:32358066, PubMed:33186557, PubMed:36369712). The coat protein complex II assembling and polymerizing on endoplasmic reticulum membrane is responsible for both the sorting of cargos and the deformation and budding of membranes into vesicles destined to the Golgi (PubMed:23433038, PubMed:32358066, PubMed:33186557). In contrast to SAR1A, SAR1B specifically interacts with the cargo receptor SURF4 to mediate the transport of lipid-carrying lipoproteins including APOB and APOA1 from the endoplasmic reticulum to the Golgi and thereby, indirectly regulates lipid homeostasis (PubMed:32358066, PubMed:33186557). In addition to its role in vesicle trafficking, can also function as a leucine sensor regulating TORC1 signaling and more indirectly cellular metabolism, growth and survival. In absence of leucine, interacts with the GATOR2 complex via MIOS and inhibits TORC1 signaling. The binding of leucine abrogates the interaction with GATOR2 and the inhibition of the TORC1 signaling. This function is completely independent of the GTPase activity of SAR1B (PubMed:34290409). {ECO:0000269|PubMed:23433038, ECO:0000269|PubMed:32358066, ECO:0000269|PubMed:33186557, ECO:0000269|PubMed:34290409, ECO:0000269|PubMed:36369712}. |
| Q9Y6D6 | ARFGEF1 | S286 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (Brefeldin A-inhibited GEP 1) (ADP-ribosylation factor guanine nucleotide-exchange factor 1) (p200 ARF guanine nucleotide exchange factor) (p200 ARF-GEP1) | Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturation of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competitive RhoA binding. The function in the nucleus remains to be determined. {ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15644318, ECO:0000269|PubMed:17227842, ECO:0000269|PubMed:20360857, ECO:0000269|PubMed:22084092}. |
| Q9Y6D6 | ARFGEF1 | S678 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (Brefeldin A-inhibited GEP 1) (ADP-ribosylation factor guanine nucleotide-exchange factor 1) (p200 ARF guanine nucleotide exchange factor) (p200 ARF-GEP1) | Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturation of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competitive RhoA binding. The function in the nucleus remains to be determined. {ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15644318, ECO:0000269|PubMed:17227842, ECO:0000269|PubMed:20360857, ECO:0000269|PubMed:22084092}. |
| Q9Y6J9 | TAF6L | S505 | ochoa | TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L (TAF6L) (PCAF-associated factor 65-alpha) (PAF65-alpha) | Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex (Probable). With TAF5L, acts as an epigenetic regulator essential for somatic reprogramming. Regulates target genes through H3K9ac deposition and MYC recruitment which trigger MYC regulatory network to orchestrate gene expression programs to control embryonic stem cell state. Functions with MYC to activate target gene expression through RNA polymerase II pause release (By similarity). {ECO:0000250|UniProtKB:Q8R2K4, ECO:0000305|PubMed:9674419}. |
| Q9Y6K1 | DNMT3A | S105 | ochoa | DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) (EC 2.1.1.37) (Cysteine methyltransferase DNMT3A) (EC 2.1.1.-) (DNA methyltransferase HsaIIIA) (DNA MTase HsaIIIA) (M.HsaIIIA) | Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation is coordinated with methylation of histones (PubMed:12138111, PubMed:16357870, PubMed:30478443). It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:12138111, PubMed:16357870, PubMed:30478443). May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (By similarity). Plays a role in paternal and maternal imprinting (By similarity). Required for methylation of most imprinted loci in germ cells (By similarity). Acts as a transcriptional corepressor for ZBTB18 (By similarity). Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (By similarity). Can actively repress transcription through the recruitment of HDAC activity (By similarity). Also has weak auto-methylation activity on Cys-710 in absence of DNA (By similarity). {ECO:0000250|UniProtKB:O88508, ECO:0000269|PubMed:12138111, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:30478443}. |
| Q9Y6K5 | OAS3 | S381 | ochoa | 2'-5'-oligoadenylate synthase 3 ((2-5')oligo(A) synthase 3) (2-5A synthase 3) (EC 2.7.7.84) (p100 OAS) (p100OAS) | Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV). {ECO:0000269|PubMed:19056102, ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:9880533}. |
| Q9Y6M4 | CSNK1G3 | S31 | ochoa | Casein kinase I isoform gamma-3 (CKI-gamma 3) (EC 2.7.11.1) | Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate (By similarity). {ECO:0000250}. |
| Q9Y6M5 | SLC30A1 | S172 | ochoa | Proton-coupled zinc antiporter SLC30A1 (Solute carrier family 30 member 1) (Zinc transporter 1) | Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444). Forms a complex with TMC6/EVER1 and TMC8/EVER2 at the ER membrane of keratynocytes which facilitates zinc uptake into the ER (PubMed:18158319). Down-regulates the activity of transcription factors induced by zinc and cytokines (PubMed:18158319). {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:18158319, ECO:0000269|PubMed:31471319, ECO:0000269|PubMed:32441444}. |
| Q9Y6R0 | NUMBL | S224 | ochoa | Numb-like protein (Numb-related protein) (Numb-R) | Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF-kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and degradation of TRAF6 in cortical neurons. {ECO:0000269|PubMed:18299187, ECO:0000269|PubMed:20079715}. |
| Q9Y6R9 | CCDC61 | S373 | ochoa | Centrosomal protein CCDC61 (Coiled-coil domain-containing protein 61) (VFL3 homolog) | Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required for anchoring microtubule at the mother centriole subdistal appendages and for centrosome positioning (PubMed:31789463). During mitosis, may be involved in spindle assembly and chromatin alignment by regulating the organization of spindle microtubules into a symmetrical structure (PubMed:30354798). Has been proposed to play a role in CEP170 recruitment to centrosomes (PubMed:30354798). However, this function could not be confirmed (PubMed:31789463). Plays a non-essential role in ciliogenesis (PubMed:31789463, PubMed:32375023). {ECO:0000269|PubMed:30354798, ECO:0000269|PubMed:31789463, ECO:0000269|PubMed:32375023}. |
| Q9Y6R9 | CCDC61 | S376 | ochoa | Centrosomal protein CCDC61 (Coiled-coil domain-containing protein 61) (VFL3 homolog) | Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker (PubMed:31789463). In interphase, required for anchoring microtubule at the mother centriole subdistal appendages and for centrosome positioning (PubMed:31789463). During mitosis, may be involved in spindle assembly and chromatin alignment by regulating the organization of spindle microtubules into a symmetrical structure (PubMed:30354798). Has been proposed to play a role in CEP170 recruitment to centrosomes (PubMed:30354798). However, this function could not be confirmed (PubMed:31789463). Plays a non-essential role in ciliogenesis (PubMed:31789463, PubMed:32375023). {ECO:0000269|PubMed:30354798, ECO:0000269|PubMed:31789463, ECO:0000269|PubMed:32375023}. |
| Q9Y6X4 | FAM169A | S526 | ochoa | Soluble lamin-associated protein of 75 kDa (SLAP75) (Protein FAM169A) | None |
| Q9Y6Y0 | IVNS1ABP | S246 | ochoa | Influenza virus NS1A-binding protein (NS1-BP) (NS1-binding protein) (Aryl hydrocarbon receptor-associated protein 3) (Kelch-like protein 39) | Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats (By similarity). Protects cells from cell death induced by actin destabilization (By similarity). Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription (PubMed:16582008). In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors (PubMed:25619834). Inhibits pre-mRNA splicing (in vitro) (PubMed:9696811). May play a role in mRNA nuclear export (PubMed:30538201). {ECO:0000250|UniProtKB:Q920Q8, ECO:0000269|PubMed:16582008, ECO:0000269|PubMed:25619834, ECO:0000269|PubMed:30538201, ECO:0000269|PubMed:9696811}.; FUNCTION: (Microbial infection) Involved in the alternative splicing of influenza A virus M1 mRNA through interaction with HNRNPK, thereby facilitating the generation of viral M2 protein (PubMed:23825951, PubMed:9696811). The BTB and Kelch domains are required for splicing activity (PubMed:30538201). Promotes export of viral M mRNA and RNP via its interaction with mRNA export factor ALYREF (PubMed:30538201). {ECO:0000269|PubMed:23825951, ECO:0000269|PubMed:30538201, ECO:0000269|PubMed:9696811}. |
| S4R3N1 | HSPE1-MOB4 | S51 | ochoa | 10 kDa heat shock protein, mitochondrial (10 kDa chaperonin) (Chaperonin 10) (MOB-like protein phocein) (Mob1 homolog 3) (Mps one binder kinase activator-like 3) (Preimplantation protein 3) | Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein. {ECO:0000256|ARBA:ARBA00046093}.; FUNCTION: Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation. {ECO:0000256|ARBA:ARBA00044741}. |
| P78371 | CCT2 | S150 | Sugiyama | T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P14314 | PRKCSH | S451 | Sugiyama | Glucosidase 2 subunit beta (80K-H protein) (Glucosidase II subunit beta) (Protein kinase C substrate 60.1 kDa protein heavy chain) (PKCSH) | Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:O08795, ECO:0000269|PubMed:10929008}. |
| P19338 | NCL | S595 | Sugiyama | Nucleolin (Protein C23) | Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}. |
| Q6EEV6 | SUMO4 | S28 | Sugiyama | Small ubiquitin-related modifier 4 (SUMO-4) (Small ubiquitin-like protein 4) | Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may modulate protein subcellular localization, stability or activity. Upon oxidative stress, conjugates to various anti-oxidant enzymes, chaperones, and stress defense proteins. May also conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their transcriptional activity, and to NR3C1, positively regulating its transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I. {ECO:0000269|PubMed:15123604, ECO:0000269|PubMed:15247916, ECO:0000269|PubMed:16236267}. |
| Q99700 | ATXN2 | S508 | Sugiyama | Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) | Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}. |
| Q7KZF4 | SND1 | S727 | Sugiyama | Staphylococcal nuclease domain-containing protein 1 (EC 3.1.31.1) (100 kDa coactivator) (EBNA2 coactivator p100) (Tudor domain-containing protein 11) (p100 co-activator) | Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (PubMed:18453631, PubMed:28546213). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition (PubMed:28546213). Functions as a bridging factor between STAT6 and the basal transcription factor (PubMed:12234934). Plays a role in PIM1 regulation of MYB activity (PubMed:9809063). Functions as a transcriptional coactivator for STAT5 (By similarity). {ECO:0000250|UniProtKB:Q78PY7, ECO:0000269|PubMed:12234934, ECO:0000269|PubMed:18453631, ECO:0000269|PubMed:28546213, ECO:0000269|PubMed:9809063}.; FUNCTION: (Microbial infection) Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2). {ECO:0000269|PubMed:7651391}.; FUNCTION: (Microbial infection) Promotes SARS-CoV-2 RNA synthesis by binding to negative-sense RNA and the viral protein nsp9. {ECO:0000269|PubMed:37794589}. |
| Q02809 | PLOD1 | S342 | Sugiyama | Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (EC 1.14.11.4) (Lysyl hydroxylase 1) (LH1) | Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (By similarity). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:10686424, PubMed:15854030, PubMed:8621606). These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links (Probable). {ECO:0000250|UniProtKB:Q9R0E2, ECO:0000269|PubMed:10686424, ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:8621606, ECO:0000305}. |
| P28066 | PSMA5 | S172 | Sugiyama | Proteasome subunit alpha type-5 (Macropain zeta chain) (Multicatalytic endopeptidase complex zeta chain) (Proteasome subunit alpha-5) (alpha-5) (Proteasome zeta chain) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P05187 | ALPP | S438 | Sugiyama | Alkaline phosphatase, placental type (EC 3.1.3.1) (Alkaline phosphatase Regan isozyme) (Placental alkaline phosphatase 1) (PLAP-1) | Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000269|PubMed:1939159, ECO:0000269|PubMed:25775211}. |
| P10696 | ALPG | S435 | Sugiyama | Alkaline phosphatase, germ cell type (EC 3.1.3.1) (ALP-1) (Alkaline phosphatase Nagao isozyme) (Alkaline phosphatase, placental-like) (Germ cell alkaline phosphatase) (GCAP) (Placental alkaline phosphatase-like) (PLAP-like) | Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000269|PubMed:1939159}. |
| P52209 | PGD | S126 | Sugiyama | 6-phosphogluconate dehydrogenase, decarboxylating (EC 1.1.1.44) | Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. {ECO:0000250}. |
| P49750 | YLPM1 | S1088 | PSP | YLP motif-containing protein 1 (Nuclear protein ZAP3) (ZAP113) | Plays a role in the reduction of telomerase activity during differentiation of embryonic stem cells by binding to the core promoter of TERT and controlling its down-regulation. {ECO:0000250}. |
| Q8IYE1 | CCDC13 | S680 | Sugiyama | Coiled-coil domain-containing protein 13 | Required for primary cilia formation and promotes the localization of the ciliopathy protein BBS4 to both centriolar satellites and cilia. {ECO:0000269|PubMed:24816561}. |
| P00519 | ABL1 | S1106 | Sugiyama | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| Q06323 | PSME1 | S31 | Sugiyama | Proteasome activator complex subunit 1 (11S regulator complex subunit alpha) (REG-alpha) (Activator of multicatalytic protease subunit 1) (Interferon gamma up-regulated I-5111 protein) (IGUP I-5111) (Proteasome activator 28 subunit alpha) (PA28a) (PA28alpha) | Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. |
| P05129 | PRKCG | S600 | Sugiyama | Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319, ECO:0000269|PubMed:16377624, ECO:0000269|PubMed:36040231}. |
| O96004 | HAND1 | S98 | ELM | Heart- and neural crest derivatives-expressed protein 1 (Class A basic helix-loop-helix protein 27) (bHLHa27) (Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1) (eHAND) | Transcription factor that plays an essential role in both trophoblast giant cell differentiation and in cardiac morphogenesis (By similarity). Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box) (By similarity). Acts as a transcriptional repressor of SOX15 (By similarity). In the adult, could be required for ongoing expression of cardiac-specific genes (PubMed:9931445). {ECO:0000250|UniProtKB:Q64279, ECO:0000269|PubMed:9931445}. |
| P08034 | GJB1 | S233 | ELM | Gap junction beta-1 protein (Connexin-32) (Cx32) (GAP junction 28 kDa liver protein) | One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. |
| P35408 | PTGER4 | S460 | ELM | Prostaglandin E2 receptor EP4 subtype (PGE receptor EP4 subtype) (PGE2 receptor EP4 subtype) (Prostanoid EP4 receptor) | Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function. |
| Q14697 | GANAB | S190 | Sugiyama | Neutral alpha-glucosidase AB (EC 3.2.1.207) (Alpha-glucosidase 2) (Glucosidase II subunit alpha) | Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:27259053). {ECO:0000269|PubMed:10929008, ECO:0000269|PubMed:27259053}. |
| Q92626 | PXDN | S918 | Sugiyama | Peroxidasin homolog (EC 1.11.2.-) (Melanoma-associated antigen MG50) (Peroxidasin 1) (hsPxd01) (Vascular peroxidase 1) (p53-responsive gene 2 protein) [Cleaved into: PXDN active fragment] | Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncross-linked collagen IV/COL4A1 NC1 hexamer (PubMed:18929642, PubMed:19590037, PubMed:22842973, PubMed:25708780, PubMed:25713063, PubMed:27697841, PubMed:28154175, PubMed:34679700). In turns, directly contributes to the collagen IV network-dependent fibronectin/FN and laminin assembly, which is required for full extracellular matrix (ECM)-mediated signaling (PubMed:19590037, PubMed:32543734, PubMed:34679700). Thus, sulfilimine cross-links are essential for growth factor-induced cell proliferation and survival in endothelial cells, an event essential to basement membrane integrity (PubMed:32543734). In addition, through the bromide oxidation, may promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and FAK pathways (PubMed:25713063). Moreover brominates alpha2 collagen IV chain/COL4A2 at 'Tyr-1485' and leads to bromine enrichment of the basement membranes (PubMed:32571911). In vitro, can also catalyze the two-electron oxidation of thiocyanate and iodide and these two substrates could effectively compete with bromide and thus inhibit the formation of sulfilimine bonds (PubMed:28154175). Binds laminins (PubMed:32485152). May play a role in the organization of eyeball structure and lens development during eye development (By similarity). {ECO:0000250|UniProtKB:Q3UQ28, ECO:0000269|PubMed:18929642, ECO:0000269|PubMed:19590037, ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:25713063, ECO:0000269|PubMed:27697841, ECO:0000269|PubMed:28154175, ECO:0000269|PubMed:32485152, ECO:0000269|PubMed:32543734, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:34679700}. |
| P14616 | INSRR | S1271 | Sugiyama | Insulin receptor-related protein (IRR) (EC 2.7.10.1) (IR-related receptor) [Cleaved into: Insulin receptor-related protein alpha chain; Insulin receptor-related protein beta chain] | Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB. {ECO:0000269|PubMed:21641549}. |
| P02686 | MBP | S190 | SIGNOR|EPSD | Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) | The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}. |
| P35368 | ADRA1B | S412 | SIGNOR|iPTMNet|EPSD | Alpha-1B adrenergic receptor (Alpha-1B adrenoreceptor) (Alpha-1B adrenoceptor) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P11168 | SLC2A2 | S505 | ELM|iPTMNet|EPSD | Solute carrier family 2, facilitated glucose transporter member 2 (Glucose transporter type 2, liver) (GLUT-2) | Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose (PubMed:16186102, PubMed:23396969, PubMed:28083649, PubMed:8027028, PubMed:8457197). Likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of the beta cell (PubMed:8027028). May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney (PubMed:3399500). Also able to mediate the transport of dehydroascorbate (PubMed:23396969). {ECO:0000269|PubMed:16186102, ECO:0000269|PubMed:23396969, ECO:0000269|PubMed:28083649, ECO:0000269|PubMed:3399500, ECO:0000269|PubMed:8027028, ECO:0000269|PubMed:8457197}. |
| P24752 | ACAT1 | S69 | Sugiyama | Acetyl-CoA acetyltransferase, mitochondrial (EC 2.3.1.9) (Acetoacetyl-CoA thiolase) (T2) | This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148, PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688, PubMed:7728148, PubMed:9744475). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a major role in ketone body metabolism (PubMed:1715688, PubMed:17371050, PubMed:7728148, PubMed:9744475). {ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. |
| Q15084 | PDIA6 | S375 | Sugiyama | Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) | May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}. |
| Q8NCN5 | PDPR | S127 | Sugiyama | Pyruvate dehydrogenase phosphatase regulatory subunit, mitochondrial (PDPr) | Decreases the sensitivity of PDP1 to magnesium ions, and this inhibition is reversed by the polyamine spermine. {ECO:0000250}. |
| P08195 | SLC3A2 | S286 | Sugiyama | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| P29322 | EPHA8 | S643 | Sugiyama | Ephrin type-A receptor 8 (EC 2.7.10.1) (EPH- and ELK-related kinase) (EPH-like kinase 3) (EK3) (hEK3) (Tyrosine-protein kinase receptor EEK) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity). {ECO:0000250}. |
| P41219 | PRPH | S59 | SIGNOR | Peripherin (Neurofilament 4) | Class-III neuronal intermediate filament protein (By similarity). May form an independent structural network without the involvement of other neurofilaments or may cooperate with the neuronal intermediate filament proteins NEFL, NEFH, NEFM and INA to form a filamentous network (PubMed:15322088, PubMed:15446584). Assembly of the neuronal intermediate filaments may be regulated by RAB7A (By similarity). Plays a role in the development of unmyelinated sensory neurons (By similarity). May be involved in axon elongation and axon regeneration after injury (By similarity). Inhibits neurite extension in type II spiral ganglion neurons in the cochlea (By similarity). {ECO:0000250|UniProtKB:P15331, ECO:0000250|UniProtKB:P21807, ECO:0000269|PubMed:15322088, ECO:0000269|PubMed:15446584}. |
| O60231 | DHX16 | S116 | Sugiyama | Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 (EC 3.6.4.13) (ATP-dependent RNA helicase #3) (DEAH-box protein 16) | Required for pre-mRNA splicing as a component of the spliceosome (PubMed:20423332, PubMed:20841358, PubMed:25296192, PubMed:29360106). Contributes to pre-mRNA splicing after spliceosome formation and prior to the first transesterification reaction. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Also plays a role in innate antiviral response by acting as a pattern recognition receptor sensing splicing signals in viral RNA (PubMed:35263596). Mechanistically, TRIM6 promotes the interaction between unanchored 'Lys-48'-polyubiquitin chains and DHX16, leading to DHX16 interaction with RIGI and ssRNA to amplify RIGI-dependent innate antiviral immune responses (PubMed:35263596). {ECO:0000269|PubMed:20423332, ECO:0000269|PubMed:20841358, ECO:0000269|PubMed:25296192, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:35263596, ECO:0000305|PubMed:33509932}. |
| Q7KZ85 | SUPT6H | S73 | Sugiyama | Transcription elongation factor SPT6 (hSPT6) (Histone chaperone suppressor of Ty6) (Tat-cotransactivator 2 protein) (Tat-CT2 protein) | Histone H3-H4 chaperone that plays a key role in the regulation of transcription elongation and mRNA processing. Enhances the transcription elongation by RNA polymerase II (RNAPII) and is also required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. Besides chaperoning histones in transcription, acts to transport and splice mRNA by forming a complex with IWS1 and the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2), to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. SUPT6H via its association with SETD1A, regulates both class-switch recombination and somatic hypermutation through formation of H3K4me3 epigenetic marks on activation-induced cytidine deaminase (AICDA) target loci. Promotes the activation of the myogenic gene program by entailing erasure of the repressive H3K27me3 epigenetic mark through stabilization of the chromatin interaction of the H3K27 demethylase KDM6A. {ECO:0000269|PubMed:15060154, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:22316138, ECO:0000269|PubMed:23503590, ECO:0000269|PubMed:9514752}. |
| Q8WYR1 | PIK3R5 | S446 | Sugiyama | Phosphoinositide 3-kinase regulatory subunit 5 (PI3-kinase regulatory subunit 5) (PI3-kinase p101 subunit) (Phosphatidylinositol 4,5-bisphosphate 3-kinase regulatory subunit) (PtdIns-3-kinase regulatory subunit) (Protein FOAP-2) (PtdIns-3-kinase p101) (p101-PI3K) | Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity). {ECO:0000250}. |
| O60829 | PAGE4 | S79 | EPSD|PSP | P antigen family member 4 (PAGE-4) (G antigen family C member 1) (PAGE-1) | Intrinsically disordered protein that potentiates the transcriptional activator activity of JUN (PubMed:24263171, PubMed:28289210). Protects cells from stress-induced apoptosis by inhibiting reactive oxygen species (ROS) production and via regulation of the MAPK signaling pathway (PubMed:21357425, PubMed:25374899, PubMed:30658679). {ECO:0000269|PubMed:21357425, ECO:0000269|PubMed:24263171, ECO:0000269|PubMed:25374899, ECO:0000269|PubMed:28289210, ECO:0000269|PubMed:30658679}. |
| P52948 | NUP98 | S872 | Sugiyama | Nuclear pore complex protein Nup98-Nup96 (EC 3.4.21.-) [Cleaved into: Nuclear pore complex protein Nup98 (98 kDa nucleoporin) (Nucleoporin Nup98) (Nup98); Nuclear pore complex protein Nup96 (96 kDa nucleoporin) (Nucleoporin Nup96) (Nup96)] | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC (PubMed:33097660). May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:33097660}.; FUNCTION: (Microbial infection) Interacts with HIV-1 capsid protein P24 and nucleocapsid protein P7 and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change Asn-74-Asp is reduced (in vitro) (PubMed:23523133). {ECO:0000269|PubMed:23523133}. |
| Q9NY33 | DPP3 | S130 | Sugiyama | Dipeptidyl peptidase 3 (EC 3.4.14.4) (Dipeptidyl aminopeptidase III) (Dipeptidyl arylamidase III) (Dipeptidyl peptidase III) (DPP III) (Enkephalinase B) | Cleaves and degrades bioactive peptides, including angiotensin, Leu-enkephalin and Met-enkephalin (PubMed:1515063, PubMed:3233187). Also cleaves Arg-Arg-beta-naphthylamide (in vitro) (PubMed:11209758, PubMed:3233187, PubMed:9425109). {ECO:0000269|PubMed:11209758, ECO:0000269|PubMed:1515063, ECO:0000269|PubMed:3233187, ECO:0000269|PubMed:9425109}. |
| P51957 | NEK4 | S772 | Sugiyama | Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) | Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}. |
| O60307 | MAST3 | S885 | Sugiyama | Microtubule-associated serine/threonine-protein kinase 3 (EC 2.7.11.1) | None |
| Q86U86 | PBRM1 | S267 | Sugiyama | Protein polybromo-1 (hPB1) (BRG1-associated factor 180) (BAF180) (Polybromo-1D) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation. {ECO:0000269|PubMed:21248752, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P57059 | SIK1 | S644 | Sugiyama | Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}. |
| Q14432 | PDE3A | S273 | Sugiyama | cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (EC 3.1.4.17) (Cyclic GMP-inhibited phosphodiesterase A) (CGI-PDE A) (cGMP-inhibited cAMP phosphodiesterase) (cGI-PDE) | Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099). {ECO:0000269|PubMed:1315035, ECO:0000269|PubMed:25961942, ECO:0000269|PubMed:27975297, ECO:0000269|PubMed:31420216, ECO:0000269|PubMed:34707099, ECO:0000269|PubMed:8155697, ECO:0000269|PubMed:8695850}. |
| P61244 | MAX | S129 | iPTMNet | Protein max (Class D basic helix-loop-helix protein 4) (bHLHd4) (Myc-associated factor X) | Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a repressor. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 'Lys-9' histone methyltransferase activity. Represses MYC transcriptional activity from E-box elements. {ECO:0000269|PubMed:26070438}. |
| Q13422 | IKZF1 | S101 | SIGNOR | DNA-binding protein Ikaros (Ikaros family zinc finger protein 1) (Lymphoid transcription factor LyF-1) | Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067). {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, ECO:0000269|PubMed:19141594}. |
| P17096 | HMGA1 | S64 | SIGNOR | High mobility group protein HMG-I/HMG-Y (HMG-I(Y)) (High mobility group AT-hook protein 1) (High mobility group protein A1) (High mobility group protein R) | HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions. |
| Q96GQ7 | DDX27 | S98 | Sugiyama | Probable ATP-dependent RNA helicase DDX27 (EC 3.6.4.13) (DEAD box protein 27) | Probable ATP-dependent RNA helicase. Component of the nucleolar ribosomal RNA (rRNA) processing machinery that regulates 3' end formation of ribosomal 47S rRNA (PubMed:25825154). {ECO:0000269|PubMed:25825154}. |
| Q13470 | TNK1 | S124 | Sugiyama | Non-receptor tyrosine-protein kinase TNK1 (EC 2.7.10.2) (CD38 negative kinase 1) | Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction. {ECO:0000269|PubMed:10873601, ECO:0000269|PubMed:18974114}. |
| Q15118 | PDK1 | S67 | Sugiyama | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 1) (PDH kinase 1) | Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2 (PubMed:7499431, PubMed:18541534, PubMed:22195962, PubMed:26942675, PubMed:17683942). This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate (PubMed:18541534, PubMed:22195962, PubMed:26942675). Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia (PubMed:18541534, PubMed:22195962, PubMed:26942675). {ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18541534, ECO:0000269|PubMed:22195962, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:7499431}. |
| Q15119 | PDK2 | S41 | Sugiyama | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 2) (PDH kinase 2) (PDKII) | Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis. {ECO:0000269|PubMed:17222789, ECO:0000269|PubMed:19833728, ECO:0000269|PubMed:21283817, ECO:0000269|PubMed:22123926, ECO:0000269|PubMed:7499431, ECO:0000269|PubMed:9787110}. |
| Q15349 | RPS6KA2 | S82 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q16539 | MAPK14 | S32 | Sugiyama | Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}. |
| O15212 | PFDN6 | S53 | Sugiyama | Prefoldin subunit 6 (Protein Ke2) | Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. {ECO:0000269|PubMed:9630229}. |
| Q16654 | PDK4 | S45 | Sugiyama | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 4) | Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism. {ECO:0000269|PubMed:15955060, ECO:0000269|PubMed:18658136, ECO:0000269|PubMed:21816445, ECO:0000269|PubMed:21852536}. |
| Q5S007 | LRRK2 | S1345 | EPSD|PSP | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| P49748 | ACADVL | S489 | Sugiyama | Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (VLCAD) (EC 1.3.8.9) | Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9599005, PubMed:9839948). The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9839948). Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 12 to 24 carbons long primary chains (PubMed:21237683, PubMed:9839948). {ECO:0000269|PubMed:18227065, ECO:0000269|PubMed:21237683, ECO:0000269|PubMed:7668252, ECO:0000269|PubMed:9461620, ECO:0000269|PubMed:9599005, ECO:0000269|PubMed:9839948}. |
| Q96AY3 | FKBP10 | S207 | Sugiyama | Peptidyl-prolyl cis-trans isomerase FKBP10 (PPIase FKBP10) (EC 5.2.1.8) (65 kDa FK506-binding protein) (65 kDa FKBP) (FKBP-65) (FK506-binding protein 10) (FKBP-10) (Immunophilin FKBP65) (Rotamase) | PPIases accelerate the folding of proteins during protein synthesis. |
| Q8N568 | DCLK2 | S129 | Sugiyama | Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) | Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}. |
| Q8N5S9 | CAMKK1 | S179 | Sugiyama | Calcium/calmodulin-dependent protein kinase kinase 1 (CaM-KK 1) (CaM-kinase kinase 1) (CaMKK 1) (EC 2.7.11.17) (CaM-kinase IV kinase) (Calcium/calmodulin-dependent protein kinase kinase alpha) (CaM-KK alpha) (CaM-kinase kinase alpha) (CaMKK alpha) | Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. {ECO:0000269|PubMed:12935886}. |
| Q8NE63 | HIPK4 | S406 | Sugiyama | Homeodomain-interacting protein kinase 4 (EC 2.7.11.1) | Protein kinase that phosphorylates human TP53 at Ser-9, and thus induces TP53 repression of BIRC5 promoter (By similarity). May act as a corepressor of transcription factors (Potential). {ECO:0000250, ECO:0000305}. |
| Q8NG66 | NEK11 | S37 | Sugiyama | Serine/threonine-protein kinase Nek11 (EC 2.7.11.1) (Never in mitosis A-related kinase 11) (NimA-related protein kinase 11) | Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation. {ECO:0000269|PubMed:12154088, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422}. |
| Q8NG66 | NEK11 | S511 | Sugiyama | Serine/threonine-protein kinase Nek11 (EC 2.7.11.1) (Never in mitosis A-related kinase 11) (NimA-related protein kinase 11) | Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation. {ECO:0000269|PubMed:12154088, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422}. |
| Q9H6T3 | RPAP3 | S348 | Sugiyama | RNA polymerase II-associated protein 3 | Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. {ECO:0000269|PubMed:17643375}. |
| Q12904 | AIMP1 | S144 | Sugiyama | Aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (Multisynthase complex auxiliary component p43) [Cleaved into: Endothelial monocyte-activating polypeptide 2 (EMAP-2) (Endothelial monocyte-activating polypeptide II) (EMAP-II) (Small inducible cytokine subfamily E member 1)] | Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase (PubMed:10358004). Binds tRNA. Possesses inflammatory cytokine activity (PubMed:11306575). Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7-mediated degradation (By similarity). Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels (By similarity). Promotes dermal fibroblast proliferation and wound repair (PubMed:16472771). Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum (By similarity). Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelian cell apoptosis at high concentrations (PubMed:12237313). Induces maturation of dendritic cells and monocyte cell adhesion (PubMed:11818442). Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7 (PubMed:19362550). {ECO:0000250|UniProtKB:P31230, ECO:0000269|PubMed:10358004, ECO:0000269|PubMed:11157763, ECO:0000269|PubMed:11306575, ECO:0000269|PubMed:11818442, ECO:0000269|PubMed:12237313, ECO:0000269|PubMed:19362550}. |
| Q96PY6 | NEK1 | S285 | Sugiyama | Serine/threonine-protein kinase Nek1 (EC 2.7.11.1) (Never in mitosis A-related kinase 1) (NimA-related protein kinase 1) (Renal carcinoma antigen NY-REN-55) | Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}. |
| Q99558 | MAP3K14 | S410 | Sugiyama | Mitogen-activated protein kinase kinase kinase 14 (EC 2.7.11.25) (NF-kappa-beta-inducing kinase) (HsNIK) (Serine/threonine-protein kinase NIK) | Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Phosphorylates CHUK/IKKA, thereby promoting proteolytic processing of NFKB2/P100, which leads to NF-kappa-B activation via the non-canonical pathway (PubMed:25406581, PubMed:29230214). Has an essential role in the non-canonical NF-kappa-B signaling that regulates genes encoding molecules involved in B-cell survival, lymphoid organogenesis, and immune response (PubMed:25406581). Could act in a receptor-selective manner. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:25406581}. |
| Q8N3D4 | EHBP1L1 | S927 | Sugiyama | EH domain-binding protein 1-like protein 1 | May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000305|PubMed:27552051}. |
| Q9H1R3 | MYLK2 | S90 | Sugiyama | Myosin light chain kinase 2, skeletal/cardiac muscle (MLCK2) (EC 2.7.11.18) | Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain. {ECO:0000269|PubMed:11733062}. |
| Q9HBH9 | MKNK2 | S166 | Sugiyama | MAP kinase-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (MAP kinase signal-integrating kinase 2) (MAPK signal-integrating kinase 2) (Mnk2) | Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}. |
| Q9NQU5 | PAK6 | S224 | Sugiyama | Serine/threonine-protein kinase PAK 6 (EC 2.7.11.1) (PAK-5) (p21-activated kinase 6) (PAK-6) | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Also inhibits ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}. |
| Q9Y570 | PPME1 | S265 | Sugiyama | Protein phosphatase methylesterase 1 (PME-1) (EC 3.1.1.89) | Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme. {ECO:0000269|PubMed:10318862}. |
| Q9Y4K4 | MAP4K5 | S28 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 5 (EC 2.7.11.1) (Kinase homologous to SPS1/STE20) (KHS) (MAPK/ERK kinase kinase kinase 5) (MEK kinase kinase 5) (MEKKK 5) | May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. {ECO:0000269|PubMed:9038372}. |
| O43741 | PRKAB2 | S39 | ochoa | 5'-AMP-activated protein kinase subunit beta-2 (AMPK subunit beta-2) | Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3). |
| O60333 | KIF1B | S1454 | ochoa | Kinesin-like protein KIF1B (Klp) (EC 5.6.1.3) | Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules. {ECO:0000269|PubMed:16225668}.; FUNCTION: [Isoform 2]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde synaptic vesicle transport along axonal microtubules from the cell body to the presynapse in neuronal cells (By similarity). Functions as a downstream effector in a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells (PubMed:18334619). {ECO:0000250|UniProtKB:Q60575, ECO:0000269|PubMed:18334619}.; FUNCTION: [Isoform 3]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde transport of mitochondria. {ECO:0000269|PubMed:16225668}. |
| O75369 | FLNB | S2113 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| P06400 | RB1 | S882 | ochoa|psp | Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110) | Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; FUNCTION: (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}. |
| P21333 | FLNA | S2158 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21796 | VDAC1 | S57 | ochoa | Non-selective voltage-gated ion channel VDAC1 (Outer mitochondrial membrane protein porin 1) (Plasmalemmal porin) (Porin 31HL) (Porin 31HM) (Voltage-dependent anion-selective channel protein 1) (VDAC-1) (hVDAC1) | Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:30061676, PubMed:8420959). The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:8420959). It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (PubMed:10661876, PubMed:18755977, PubMed:8420959). The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:18755977, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:18755977, PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Mediates cytochrome c efflux (PubMed:20230784). {ECO:0000250|UniProtKB:Q60932, ECO:0000269|PubMed:10661876, ECO:0000269|PubMed:11845315, ECO:0000269|PubMed:15033708, ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:25296756, ECO:0000269|PubMed:30061676, ECO:0000269|PubMed:31015432, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:8420959}.; FUNCTION: Catalyzes the scrambling of phospholipids across the outer mitochondrial membrane; the mechanism is unrelated to channel activity and is capable of translocating both anionic and zwitterionic phospholipids. {ECO:0000269|PubMed:38065946}. |
| P23497 | SP100 | S231 | ochoa | Nuclear autoantigen Sp-100 (Nuclear dot-associated Sp100 protein) (Speckled 100 kDa) | Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation. {ECO:0000269|PubMed:11909962, ECO:0000269|PubMed:14647468, ECO:0000269|PubMed:15247905, ECO:0000269|PubMed:15592518, ECO:0000269|PubMed:15767676, ECO:0000269|PubMed:16177824, ECO:0000269|PubMed:17245429, ECO:0000269|PubMed:21274506, ECO:0000269|PubMed:21880768}. |
| P28749 | RBL1 | S1009 | psp | Retinoblastoma-like protein 1 (107 kDa retinoblastoma-associated protein) (p107) (pRb1) | Key regulator of entry into cell division (PubMed:17671431). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (By similarity). Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression (By similarity). Controls histone H4 'Lys-20' trimethylation (By similarity). Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters (By similarity). Potent inhibitor of E2F-mediated trans-activation (PubMed:8319904). May act as a tumor suppressor (PubMed:8319904). {ECO:0000250|UniProtKB:Q64701, ECO:0000269|PubMed:17671431, ECO:0000269|PubMed:8319904}. |
| P29317 | EPHA2 | S901 | ochoa | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P38398 | BRCA1 | S425 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P49116 | NR2C2 | S46 | ochoa | Nuclear receptor subfamily 2 group C member 2 (Orphan nuclear receptor TAK1) (Orphan nuclear receptor TR4) (Testicular receptor 4) | Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation. {ECO:0000250, ECO:0000269|PubMed:10347174, ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:17974920, ECO:0000269|PubMed:7779113, ECO:0000269|PubMed:9556573}. |
| P51116 | FXR2 | S601 | ochoa | RNA-binding protein FXR2 (FXR2P) (FMR1 autosomal homolog 2) | mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for adult hippocampal neurogenesis (By similarity). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs: mRNAs storage into membraneless compartments regulates their translation and/or stability (By similarity). Acts as a regulator of adult hippocampal neurogenesis by regulating translation and/or stability of NOG mRNA, thereby preventing NOG protein expression in the dentate gyrus (By similarity). {ECO:0000250|UniProtKB:Q61584, ECO:0000250|UniProtKB:Q9WVR4}. |
| P55082 | MFAP3 | S334 | ochoa | Microfibril-associated glycoprotein 3 | Component of the elastin-associated microfibrils. |
| Q13177 | PAK2 | S64 | ochoa|psp | Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. |
| Q14244 | MAP7 | S169 | ochoa | Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) | Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}. |
| Q14244 | MAP7 | S657 | ochoa | Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) | Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}. |
| Q14669 | TRIP12 | S163 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14839 | CHD4 | S1349 | ochoa|psp | Chromodomain-helicase-DNA-binding protein 4 (CHD-4) (EC 3.6.4.-) (ATP-dependent helicase CHD4) (Mi-2 autoantigen 218 kDa protein) (Mi2-beta) | ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA (PubMed:28977666, PubMed:32543371). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:17626165, PubMed:28977666, PubMed:9804427). Localizes to acetylated damaged chromatin in a ZMYND8-dependent manner, to promote transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309). Involved in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q6PDQ2, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:32543371, ECO:0000269|PubMed:9804427}. |
| Q15349 | RPS6KA2 | S546 | ochoa | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q16831 | UPP1 | S61 | ochoa | Uridine phosphorylase 1 (UPase 1) (UrdPase 1) (EC 2.4.2.3) | Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (PubMed:7488099). Shows broad substrate specificity and can also accept deoxyuridine and other analogous compounds (Probable). {ECO:0000269|PubMed:7488099, ECO:0000305|PubMed:13737038}. |
| Q16877 | PFKFB4 | S176 | ochoa | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (6PF-2-K/Fru-2,6-P2ase 4) (PFK/FBPase 4) (6PF-2-K/Fru-2,6-P2ase testis-type isozyme) [Includes: 6-phosphofructo-2-kinase (EC 2.7.1.105); Fructose-2,6-bisphosphatase (EC 3.1.3.46)] | Synthesis and degradation of fructose 2,6-bisphosphate. |
| Q3MHD2 | LSM12 | S157 | ochoa | Protein LSM12 | Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein (PubMed:34362892). Confers NAADP sensitivity to the two pore channel complex (TPCs) by acting as TPC accessory protein necessary for NAADP-evoked Ca(2+) release (PubMed:34362892). {ECO:0000269|PubMed:34362892}. |
| Q3V6T2 | CCDC88A | S1678 | ochoa | Girdin (Akt phosphorylation enhancer) (APE) (Coiled-coil domain-containing protein 88A) (G alpha-interacting vesicle-associated protein) (GIV) (Girders of actin filament) (Hook-related protein 1) (HkRP1) | Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:16139227, PubMed:19211784, PubMed:20462955, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}. |
| Q56P03 | EAPP | S87 | ochoa | E2F-associated phosphoprotein (EAPP) | May play an important role in the fine-tuning of both major E2F1 activities, the regulation of the cell-cycle and the induction of apoptosis. Promotes S-phase entry, and inhibits p14(ARP) expression. {ECO:0000269|PubMed:15716352}. |
| Q5H8A4 | PIGG | S639 | ochoa | GPI ethanolamine phosphate transferase 2, catalytic subunit (EC 2.-.-.-) (GPI7 homolog) (hGPI7) (Phosphatidylinositol-glycan biosynthesis class G protein) (PIG-G) | Catalytic subunit of the ethanolamine phosphate transferase 2 complex that transfers an ethanolamine phosphate (EtNP) from a phosphatidylethanolamine (PE) to the 6-OH position of the second alpha-1,6-linked mannose of a 6-PEtn-alpha-D-Man-(1->2)-alpha-D-Man-(1->6)-2-PEtn-alpha-D-Man-(1->4)-alpha-D-GlcN-(1->6)-(1-radyl,2-acyl-sn-glycero-3-phospho)-2-acyl-inositol (also termed H7) intermediate to generate a 6-PEtn-alpha-D-Man-(1->2)-6-PEtn-alpha-D-Man-(1->6)-2-PEtn-alpha-D-Man-(1->4)-alpha-D-GlcN-(1->6)-(1-radyl,2-acyl-sn-glycero-3-phospho)-2-acyl-inositol (also termed H8) and participates in the eleventh step of the glycosylphosphatidylinositol-anchor biosynthesis. {ECO:0000269|PubMed:15632136, ECO:0000269|PubMed:26996948, ECO:0000269|PubMed:33763700, ECO:0000269|PubMed:34113002}. |
| Q5JSH3 | WDR44 | S27 | ochoa | WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) | Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| Q5T7W0 | ZNF618 | S120 | ochoa | Zinc finger protein 618 | Regulates UHRF2 function as a specific 5-hydroxymethylcytosine (5hmC) reader by regulating its chromatin localization. {ECO:0000269|PubMed:27129234}. |
| Q63HN8 | RNF213 | S2904 | ochoa | E3 ubiquitin-protein ligase RNF213 (EC 2.3.2.27) (EC 3.6.4.-) (ALK lymphoma oligomerization partner on chromosome 17) (E3 ubiquitin-lipopolysaccharide ligase RNF213) (EC 2.3.2.-) (Mysterin) (RING finger protein 213) | Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115). {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, ECO:0000269|PubMed:26766444, ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:30846318, ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849, ECO:0000269|PubMed:34012115}. |
| Q66K14 | TBC1D9B | S1138 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q6ZNL6 | FGD5 | S1330 | ochoa | FYVE, RhoGEF and PH domain-containing protein 5 (Zinc finger FYVE domain-containing protein 23) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Mediates VEGF-induced CDC42 activation. May regulate proangiogenic action of VEGF in vascular endothelial cells, including network formation, directional movement and proliferation. May play a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:22328776}. |
| Q86UX6 | STK32C | S70 | ochoa | Serine/threonine-protein kinase 32C (EC 2.7.11.1) (PKE) (Yet another novel kinase 3) | None |
| Q8IU60 | DCP2 | S284 | ochoa | m7GpppN-mRNA hydrolase (EC 3.6.1.62) (Nucleoside diphosphate-linked moiety X motif 20) (Nudix motif 20) (mRNA-decapping enzyme 2) (hDpc) | Decapping metalloenzyme that catalyzes the cleavage of the cap structure on mRNAs (PubMed:12218187, PubMed:12417715, PubMed:12923261, PubMed:21070968, PubMed:28002401, PubMed:31875550). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12486012, PubMed:12923261, PubMed:21070968, PubMed:28002401, PubMed:31875550). Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:14527413). Plays a role in replication-dependent histone mRNA degradation (PubMed:18172165). Has higher activity towards mRNAs that lack a poly(A) tail (PubMed:21070968). Has no activity towards a cap structure lacking an RNA moiety (PubMed:21070968). The presence of a N(6)-methyladenosine methylation at the second transcribed position of mRNAs (N(6),2'-O-dimethyladenosine cap; m6A(m)) provides resistance to DCP2-mediated decapping (PubMed:28002401). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573). {ECO:0000269|PubMed:12218187, ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:12486012, ECO:0000269|PubMed:12923261, ECO:0000269|PubMed:14527413, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:26098573, ECO:0000269|PubMed:28002401}. |
| Q8IVT5 | KSR1 | S334 | ochoa | Kinase suppressor of Ras 1 (EC 2.7.11.1) | Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity). Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (PubMed:29433126). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (By similarity). Its kinase activity is unsure (By similarity). Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (By similarity). {ECO:0000250|UniProtKB:Q61097, ECO:0000269|PubMed:29433126}. |
| Q8N3J3 | HROB | S351 | ochoa | Homologous recombination OB-fold protein | DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis. {ECO:0000269|PubMed:31467087}. |
| Q8N3Z6 | ZCCHC7 | S485 | ochoa | Zinc finger CCHC domain-containing protein 7 (TRAMP-like complex RNA-binding factor ZCCHC7) | None |
| Q8TBB1 | LNX1 | S441 | ochoa | E3 ubiquitin-protein ligase LNX (EC 2.3.2.27) (Ligand of Numb-protein X 1) (Numb-binding protein 1) (PDZ domain-containing RING finger protein 2) (RING-type E3 ubiquitin transferase LNX) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65. {ECO:0000250|UniProtKB:O70263}.; FUNCTION: Isoform 2 provides an endocytic scaffold for IGSF5/JAM4. {ECO:0000250|UniProtKB:O70263}. |
| Q8TCG2 | PI4K2B | S45 | ochoa | Phosphatidylinositol 4-kinase type 2-beta (EC 2.7.1.67) (Phosphatidylinositol 4-kinase type II-beta) (PI4KII-BETA) | Together with PI4K2A and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell (PubMed:11923287, PubMed:12324459). This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments (PubMed:11923287, PubMed:12324459). The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3) (PubMed:11923287, PubMed:12324459). Contributes to the production of InsP3 in stimulated cells and is likely to be involved in the regulation of vesicular trafficking. {ECO:0000269|PubMed:11923287, ECO:0000269|PubMed:12324459}. |
| Q8TCT0 | CERK | S340 | ochoa|psp | Ceramide kinase (hCERK) (EC 2.7.1.138) (Acylsphingosine kinase) (Lipid kinase 4) (LK4) | Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate (PubMed:11956206, PubMed:16269826, PubMed:19168031). Acts efficiently on natural and analog ceramides (C6, C8, C16 ceramides, and C8-dihydroceramide), to a lesser extent on C2-ceramide and C6-dihydroceramide, but not on other lipids, such as various sphingosines (PubMed:11956206, PubMed:16269826, PubMed:19168031). Shows a greater preference for D-erythro isomer of ceramides (PubMed:16269826). Binds phosphoinositides (PubMed:19168031). {ECO:0000269|PubMed:11956206, ECO:0000269|PubMed:16269826, ECO:0000269|PubMed:19168031}. |
| Q92610 | ZNF592 | S412 | ochoa | Zinc finger protein 592 | May be involved in transcriptional regulation. {ECO:0000269|PubMed:20531441}. |
| Q92614 | MYO18A | S987 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q96CA5 | BIRC7 | S37 | ochoa | Baculoviral IAP repeat-containing protein 7 (EC 2.3.2.27) (Kidney inhibitor of apoptosis protein) (KIAP) (Livin) (Melanoma inhibitor of apoptosis protein) (ML-IAP) (RING finger protein 50) (RING-type E3 ubiquitin transferase BIRC7) [Cleaved into: Baculoviral IAP repeat-containing protein 7 30kDa subunit (Truncated livin) (p30-Livin) (tLivin)] | Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control (PubMed:11024045, PubMed:11084335, PubMed:11162435, PubMed:16729033, PubMed:17294084). Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity (PubMed:11024045, PubMed:16729033). As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival (PubMed:16729033). May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions (PubMed:16729033). Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine (PubMed:11084335, PubMed:11162435, PubMed:11865055). Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2 (PubMed:11865055). This activation depends on TAB1 and MAP3K7/TAK1 (PubMed:11865055). In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9 (PubMed:11024045). {ECO:0000269|PubMed:11024045, ECO:0000269|PubMed:11084335, ECO:0000269|PubMed:11162435, ECO:0000269|PubMed:11865055, ECO:0000269|PubMed:16729033, ECO:0000269|PubMed:17294084}.; FUNCTION: [Isoform 1]: Blocks staurosporine-induced apoptosis (PubMed:11322947). Promotes natural killer (NK) cell-mediated killing (PubMed:18034418). {ECO:0000269|PubMed:11322947, ECO:0000269|PubMed:18034418}.; FUNCTION: [Isoform 2]: Blocks etoposide-induced apoptosis (PubMed:11162435, PubMed:11322947). Protects against natural killer (NK) cell-mediated killing (PubMed:18034418). {ECO:0000269|PubMed:11162435, ECO:0000269|PubMed:11322947, ECO:0000269|PubMed:18034418}. |
| Q96KG9 | SCYL1 | S41 | ochoa | N-terminal kinase-like protein (Coated vesicle-associated kinase of 90 kDa) (SCY1-like protein 1) (Telomerase regulation-associated protein) (Telomerase transcriptional element-interacting factor) (Teratoma-associated tyrosine kinase) | Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). {ECO:0000269|PubMed:18556652, ECO:0000269|PubMed:26581903}.; FUNCTION: [Isoform 6]: Acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region. {ECO:0000269|PubMed:15963946}. |
| Q96ST3 | SIN3A | S860 | ochoa | Paired amphipathic helix protein Sin3a (Histone deacetylase complex subunit Sin3a) (Transcriptional corepressor Sin3a) | Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (By similarity). Required for cortical neuron differentiation and callosal axon elongation (By similarity). {ECO:0000250|UniProtKB:Q60520, ECO:0000269|PubMed:12150998}. |
| Q9HCP0 | CSNK1G1 | S31 | ochoa | Casein kinase I isoform gamma-1 (CKI-gamma 1) (EC 2.7.11.1) | Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate (By similarity). Phosphorylates CLSPN. {ECO:0000250, ECO:0000269|PubMed:21680713}. |
| Q9NX01 | TXNL4B | S96 | ochoa | Thioredoxin-like protein 4B (Dim1-like protein) | Essential role in pre-mRNA splicing. Required in cell cycle progression for S/G(2) transition. {ECO:0000269|PubMed:15161931}. |
| Q9NX95 | SYBU | S107 | ochoa | Syntabulin (Golgi-localized syntaphilin-related protein) (Syntaxin-1-binding protein) | Part of a kinesin motor-adapter complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development. {ECO:0000250, ECO:0000269|PubMed:15459722}. |
| Q9P2E9 | RRBP1 | S573 | ochoa | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| Q9UDY4 | DNAJB4 | S248 | ochoa | DnaJ homolog subfamily B member 4 (Heat shock 40 kDa protein 1 homolog) (HSP40 homolog) (Heat shock protein 40 homolog) (Human liver DnaJ-like protein) | Probable chaperone. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro) (PubMed:24318877). {ECO:0000269|PubMed:24318877}. |
| Q9Y462 | ZNF711 | S230 | ochoa | Zinc finger protein 711 (Zinc finger protein 6) | Transcription regulator required for brain development (PubMed:20346720). Probably acts as a transcription factor that binds to the promoter of target genes and recruits PHF8 histone demethylase, leading to activated expression of genes involved in neuron development, such as KDM5C (PubMed:20346720, PubMed:31691806). May compete with transcription factor ARX for activation of expression of KDM5C (PubMed:31691806). {ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:31691806}. |
| Q9Y6K1 | DNMT3A | S267 | ochoa | DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) (EC 2.1.1.37) (Cysteine methyltransferase DNMT3A) (EC 2.1.1.-) (DNA methyltransferase HsaIIIA) (DNA MTase HsaIIIA) (M.HsaIIIA) | Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:12138111, PubMed:16357870, PubMed:30478443). DNA methylation is coordinated with methylation of histones (PubMed:12138111, PubMed:16357870, PubMed:30478443). It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:12138111, PubMed:16357870, PubMed:30478443). May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (By similarity). Plays a role in paternal and maternal imprinting (By similarity). Required for methylation of most imprinted loci in germ cells (By similarity). Acts as a transcriptional corepressor for ZBTB18 (By similarity). Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (By similarity). Can actively repress transcription through the recruitment of HDAC activity (By similarity). Also has weak auto-methylation activity on Cys-710 in absence of DNA (By similarity). {ECO:0000250|UniProtKB:O88508, ECO:0000269|PubMed:12138111, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:30478443}. |
| P14625 | HSP90B1 | S544 | Sugiyama | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-1640170 | Cell Cycle | 9.436896e-15 | 14.025 |
| R-HSA-69278 | Cell Cycle, Mitotic | 1.754152e-14 | 13.756 |
| R-HSA-68886 | M Phase | 1.063261e-11 | 10.973 |
| R-HSA-8953897 | Cellular responses to stimuli | 5.565792e-11 | 10.254 |
| R-HSA-2262752 | Cellular responses to stress | 1.787368e-10 | 9.748 |
| R-HSA-69620 | Cell Cycle Checkpoints | 3.572432e-09 | 8.447 |
| R-HSA-75153 | Apoptotic execution phase | 1.737653e-08 | 7.760 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 2.451953e-08 | 7.610 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 3.373376e-08 | 7.472 |
| R-HSA-438064 | Post NMDA receptor activation events | 4.821556e-08 | 7.317 |
| R-HSA-68877 | Mitotic Prometaphase | 6.381664e-08 | 7.195 |
| R-HSA-69275 | G2/M Transition | 6.838642e-08 | 7.165 |
| R-HSA-199991 | Membrane Trafficking | 1.047432e-07 | 6.980 |
| R-HSA-162582 | Signal Transduction | 1.792600e-07 | 6.747 |
| R-HSA-68882 | Mitotic Anaphase | 3.107852e-07 | 6.508 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 3.666076e-07 | 6.436 |
| R-HSA-422475 | Axon guidance | 3.561535e-07 | 6.448 |
| R-HSA-2467813 | Separation of Sister Chromatids | 4.631960e-07 | 6.334 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 5.342550e-07 | 6.272 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 5.623959e-07 | 6.250 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 7.600629e-07 | 6.119 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 9.622155e-07 | 6.017 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 9.676762e-07 | 6.014 |
| R-HSA-983189 | Kinesins | 1.013516e-06 | 5.994 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 1.107319e-06 | 5.956 |
| R-HSA-9675108 | Nervous system development | 1.105266e-06 | 5.957 |
| R-HSA-437239 | Recycling pathway of L1 | 2.239504e-06 | 5.650 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 2.738085e-06 | 5.563 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 3.157466e-06 | 5.501 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 3.728797e-06 | 5.428 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 4.636163e-06 | 5.334 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 4.856666e-06 | 5.314 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 5.991026e-06 | 5.222 |
| R-HSA-72172 | mRNA Splicing | 6.112566e-06 | 5.214 |
| R-HSA-9700206 | Signaling by ALK in cancer | 6.459446e-06 | 5.190 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 6.459446e-06 | 5.190 |
| R-HSA-69481 | G2/M Checkpoints | 8.235798e-06 | 5.084 |
| R-HSA-2559583 | Cellular Senescence | 8.609348e-06 | 5.065 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 8.955028e-06 | 5.048 |
| R-HSA-3371556 | Cellular response to heat stress | 8.799371e-06 | 5.056 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 1.039415e-05 | 4.983 |
| R-HSA-9663891 | Selective autophagy | 1.171976e-05 | 4.931 |
| R-HSA-193648 | NRAGE signals death through JNK | 1.414556e-05 | 4.849 |
| R-HSA-68875 | Mitotic Prophase | 1.466912e-05 | 4.834 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 1.596832e-05 | 4.797 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 1.596832e-05 | 4.797 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 1.654387e-05 | 4.781 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 1.841879e-05 | 4.735 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 1.839664e-05 | 4.735 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 2.284556e-05 | 4.641 |
| R-HSA-5688426 | Deubiquitination | 2.715151e-05 | 4.566 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 3.518423e-05 | 4.454 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 3.604373e-05 | 4.443 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 3.784508e-05 | 4.422 |
| R-HSA-2028269 | Signaling by Hippo | 3.784508e-05 | 4.422 |
| R-HSA-3247509 | Chromatin modifying enzymes | 4.185756e-05 | 4.378 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 4.274858e-05 | 4.369 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 5.513736e-05 | 4.259 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 5.585202e-05 | 4.253 |
| R-HSA-4839726 | Chromatin organization | 5.841886e-05 | 4.233 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 6.178999e-05 | 4.209 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.422097e-05 | 4.192 |
| R-HSA-3371568 | Attenuation phase | 7.170109e-05 | 4.144 |
| R-HSA-9646399 | Aggrephagy | 7.170109e-05 | 4.144 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 6.988214e-05 | 4.156 |
| R-HSA-8953854 | Metabolism of RNA | 7.221110e-05 | 4.141 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 8.065426e-05 | 4.093 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 8.304756e-05 | 4.081 |
| R-HSA-73887 | Death Receptor Signaling | 9.640811e-05 | 4.016 |
| R-HSA-373760 | L1CAM interactions | 1.050302e-04 | 3.979 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 1.273173e-04 | 3.895 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 1.273173e-04 | 3.895 |
| R-HSA-3371571 | HSF1-dependent transactivation | 1.335097e-04 | 3.874 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 1.413600e-04 | 3.850 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 1.451664e-04 | 3.838 |
| R-HSA-1500931 | Cell-Cell communication | 1.451785e-04 | 3.838 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 1.559138e-04 | 3.807 |
| R-HSA-9833482 | PKR-mediated signaling | 1.685758e-04 | 3.773 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 1.754133e-04 | 3.756 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 1.896571e-04 | 3.722 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 1.914448e-04 | 3.718 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 2.166273e-04 | 3.664 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 2.256781e-04 | 3.647 |
| R-HSA-380287 | Centrosome maturation | 2.662751e-04 | 3.575 |
| R-HSA-109581 | Apoptosis | 2.949830e-04 | 3.530 |
| R-HSA-3214847 | HATs acetylate histones | 3.224855e-04 | 3.491 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.224855e-04 | 3.491 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 3.363409e-04 | 3.473 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 3.481907e-04 | 3.458 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 3.567758e-04 | 3.448 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 3.991448e-04 | 3.399 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 4.211574e-04 | 3.376 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 4.688178e-04 | 3.329 |
| R-HSA-5689880 | Ub-specific processing proteases | 4.841337e-04 | 3.315 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 4.850987e-04 | 3.314 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 5.616895e-04 | 3.251 |
| R-HSA-9612973 | Autophagy | 6.556518e-04 | 3.183 |
| R-HSA-1632852 | Macroautophagy | 6.740804e-04 | 3.171 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 6.978854e-04 | 3.156 |
| R-HSA-190828 | Gap junction trafficking | 7.076298e-04 | 3.150 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 7.959111e-04 | 3.099 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 7.959111e-04 | 3.099 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 8.000397e-04 | 3.097 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 8.154524e-04 | 3.089 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 8.352166e-04 | 3.078 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 8.375716e-04 | 3.077 |
| R-HSA-774815 | Nucleosome assembly | 9.000597e-04 | 3.046 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 9.000597e-04 | 3.046 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 9.294208e-04 | 3.032 |
| R-HSA-416482 | G alpha (12/13) signalling events | 9.600267e-04 | 3.018 |
| R-HSA-3371511 | HSF1 activation | 9.633472e-04 | 3.016 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 1.057444e-03 | 2.976 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 1.034293e-03 | 2.985 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 1.034293e-03 | 2.985 |
| R-HSA-157858 | Gap junction trafficking and regulation | 1.008086e-03 | 2.997 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 1.123598e-03 | 2.949 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 1.123598e-03 | 2.949 |
| R-HSA-140342 | Apoptosis induced DNA fragmentation | 1.154165e-03 | 2.938 |
| R-HSA-5653656 | Vesicle-mediated transport | 1.175906e-03 | 2.930 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 1.205427e-03 | 2.919 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 1.247325e-03 | 2.904 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 1.382275e-03 | 2.859 |
| R-HSA-190861 | Gap junction assembly | 1.382275e-03 | 2.859 |
| R-HSA-180746 | Nuclear import of Rev protein | 1.382275e-03 | 2.859 |
| R-HSA-162906 | HIV Infection | 1.295438e-03 | 2.888 |
| R-HSA-211000 | Gene Silencing by RNA | 1.344639e-03 | 2.871 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 1.428014e-03 | 2.845 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 1.433520e-03 | 2.844 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 1.442709e-03 | 2.841 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 1.460451e-03 | 2.836 |
| R-HSA-5693538 | Homology Directed Repair | 1.554806e-03 | 2.808 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 1.572710e-03 | 2.803 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 1.603760e-03 | 2.795 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 1.659142e-03 | 2.780 |
| R-HSA-5633007 | Regulation of TP53 Activity | 1.746335e-03 | 2.758 |
| R-HSA-2132295 | MHC class II antigen presentation | 1.769068e-03 | 2.752 |
| R-HSA-446728 | Cell junction organization | 1.780583e-03 | 2.749 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 1.786569e-03 | 2.748 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.803885e-03 | 2.744 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 1.837336e-03 | 2.736 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 1.908530e-03 | 2.719 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 1.984828e-03 | 2.702 |
| R-HSA-391251 | Protein folding | 2.011619e-03 | 2.696 |
| R-HSA-5693606 | DNA Double Strand Break Response | 1.989645e-03 | 2.701 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 2.068961e-03 | 2.684 |
| R-HSA-1489509 | DAG and IP3 signaling | 2.008537e-03 | 2.697 |
| R-HSA-162909 | Host Interactions of HIV factors | 2.015838e-03 | 2.696 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 2.137555e-03 | 2.670 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 2.141418e-03 | 2.669 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 2.176577e-03 | 2.662 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 2.191681e-03 | 2.659 |
| R-HSA-111933 | Calmodulin induced events | 2.289680e-03 | 2.640 |
| R-HSA-111997 | CaM pathway | 2.289680e-03 | 2.640 |
| R-HSA-70171 | Glycolysis | 2.365236e-03 | 2.626 |
| R-HSA-5610787 | Hedgehog 'off' state | 2.365236e-03 | 2.626 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 2.560844e-03 | 2.592 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 2.614158e-03 | 2.583 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 2.413575e-03 | 2.617 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 2.671864e-03 | 2.573 |
| R-HSA-9700645 | ALK mutants bind TKIs | 2.671864e-03 | 2.573 |
| R-HSA-426496 | Post-transcriptional silencing by small RNAs | 2.673023e-03 | 2.573 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 2.852320e-03 | 2.545 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 2.852320e-03 | 2.545 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 2.904320e-03 | 2.537 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 2.909541e-03 | 2.536 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 2.989739e-03 | 2.524 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 3.132129e-03 | 2.504 |
| R-HSA-3214815 | HDACs deacetylate histones | 3.456167e-03 | 2.461 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 3.505346e-03 | 2.455 |
| R-HSA-1538133 | G0 and Early G1 | 3.669778e-03 | 2.435 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 3.717246e-03 | 2.430 |
| R-HSA-5334118 | DNA methylation | 4.102557e-03 | 2.387 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 3.804809e-03 | 2.420 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 4.129816e-03 | 2.384 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 3.759507e-03 | 2.425 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 3.968163e-03 | 2.401 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 4.133829e-03 | 2.384 |
| R-HSA-9909396 | Circadian clock | 4.139396e-03 | 2.383 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 4.145088e-03 | 2.382 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 4.245246e-03 | 2.372 |
| R-HSA-5357801 | Programmed Cell Death | 4.268541e-03 | 2.370 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 4.295224e-03 | 2.367 |
| R-HSA-194138 | Signaling by VEGF | 4.296599e-03 | 2.367 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 4.520572e-03 | 2.345 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 4.563334e-03 | 2.341 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 4.670547e-03 | 2.331 |
| R-HSA-1221632 | Meiotic synapsis | 4.780903e-03 | 2.320 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 4.640474e-03 | 2.333 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 4.543850e-03 | 2.343 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 4.778058e-03 | 2.321 |
| R-HSA-111996 | Ca-dependent events | 4.914085e-03 | 2.309 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 4.507947e-03 | 2.346 |
| R-HSA-5617833 | Cilium Assembly | 4.830131e-03 | 2.316 |
| R-HSA-376176 | Signaling by ROBO receptors | 4.828962e-03 | 2.316 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 4.548869e-03 | 2.342 |
| R-HSA-162587 | HIV Life Cycle | 4.990122e-03 | 2.302 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 5.177199e-03 | 2.286 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 5.377709e-03 | 2.269 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 5.402377e-03 | 2.267 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 5.522872e-03 | 2.258 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 5.621343e-03 | 2.250 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 5.883400e-03 | 2.230 |
| R-HSA-5683057 | MAPK family signaling cascades | 5.940861e-03 | 2.226 |
| R-HSA-70326 | Glucose metabolism | 6.465642e-03 | 2.189 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 7.305618e-03 | 2.136 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 7.324095e-03 | 2.135 |
| R-HSA-8852135 | Protein ubiquitination | 7.336878e-03 | 2.134 |
| R-HSA-69242 | S Phase | 7.365294e-03 | 2.133 |
| R-HSA-389948 | Co-inhibition by PD-1 | 8.050635e-03 | 2.094 |
| R-HSA-164944 | Nef and signal transduction | 8.769929e-03 | 2.057 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 8.282720e-03 | 2.082 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 9.070753e-03 | 2.042 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 8.236834e-03 | 2.084 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 9.094561e-03 | 2.041 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 9.094561e-03 | 2.041 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 8.282720e-03 | 2.082 |
| R-HSA-112043 | PLC beta mediated events | 9.661253e-03 | 2.015 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 9.745905e-03 | 2.011 |
| R-HSA-9930044 | Nuclear RNA decay | 1.039866e-02 | 1.983 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 1.050842e-02 | 1.978 |
| R-HSA-525793 | Myogenesis | 1.083819e-02 | 1.965 |
| R-HSA-72649 | Translation initiation complex formation | 1.102254e-02 | 1.958 |
| R-HSA-8853659 | RET signaling | 1.111237e-02 | 1.954 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 1.111237e-02 | 1.954 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 1.131722e-02 | 1.946 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 1.159301e-02 | 1.936 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 1.187890e-02 | 1.925 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 1.209997e-02 | 1.917 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 1.228304e-02 | 1.911 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 1.233756e-02 | 1.909 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 1.249987e-02 | 1.903 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 1.433439e-02 | 1.844 |
| R-HSA-4641258 | Degradation of DVL | 1.349966e-02 | 1.870 |
| R-HSA-9948299 | Ribosome-associated quality control | 1.361214e-02 | 1.866 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 1.360620e-02 | 1.866 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 1.310330e-02 | 1.883 |
| R-HSA-373755 | Semaphorin interactions | 1.308984e-02 | 1.883 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 1.308984e-02 | 1.883 |
| R-HSA-8848021 | Signaling by PTK6 | 1.308984e-02 | 1.883 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 1.349966e-02 | 1.870 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 1.433439e-02 | 1.844 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 1.396296e-02 | 1.855 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 1.393940e-02 | 1.856 |
| R-HSA-5358351 | Signaling by Hedgehog | 1.361214e-02 | 1.866 |
| R-HSA-9020591 | Interleukin-12 signaling | 1.479813e-02 | 1.830 |
| R-HSA-6807070 | PTEN Regulation | 1.497995e-02 | 1.824 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 1.497995e-02 | 1.824 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 1.510580e-02 | 1.821 |
| R-HSA-164378 | PKA activation in glucagon signalling | 1.556228e-02 | 1.808 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 1.556228e-02 | 1.808 |
| R-HSA-381070 | IRE1alpha activates chaperones | 1.569258e-02 | 1.804 |
| R-HSA-195721 | Signaling by WNT | 1.597588e-02 | 1.797 |
| R-HSA-9645723 | Diseases of programmed cell death | 1.601226e-02 | 1.796 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 1.679762e-02 | 1.775 |
| R-HSA-5368598 | Negative regulation of TCF-dependent signaling by DVL-interacting proteins | 1.684789e-02 | 1.773 |
| R-HSA-9944997 | Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome | 1.684789e-02 | 1.773 |
| R-HSA-9944971 | Loss of Function of KMT2D in Kabuki Syndrome | 1.684789e-02 | 1.773 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 1.713687e-02 | 1.766 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 1.713687e-02 | 1.766 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 1.742658e-02 | 1.759 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 1.750795e-02 | 1.757 |
| R-HSA-418990 | Adherens junctions interactions | 1.809150e-02 | 1.743 |
| R-HSA-913531 | Interferon Signaling | 1.892697e-02 | 1.723 |
| R-HSA-1059683 | Interleukin-6 signaling | 1.903841e-02 | 1.720 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 1.944225e-02 | 1.711 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 1.945765e-02 | 1.711 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 1.945765e-02 | 1.711 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 1.948202e-02 | 1.710 |
| R-HSA-9839394 | TGFBR3 expression | 1.948202e-02 | 1.710 |
| R-HSA-9620244 | Long-term potentiation | 1.948202e-02 | 1.710 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 2.062042e-02 | 1.686 |
| R-HSA-446107 | Type I hemidesmosome assembly | 2.129629e-02 | 1.672 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 2.129629e-02 | 1.672 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 2.049942e-02 | 1.688 |
| R-HSA-9675151 | Disorders of Developmental Biology | 2.278537e-02 | 1.642 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 2.278537e-02 | 1.642 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 2.082979e-02 | 1.681 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 2.184832e-02 | 1.661 |
| R-HSA-210990 | PECAM1 interactions | 2.049942e-02 | 1.688 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 2.029740e-02 | 1.693 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 2.161019e-02 | 1.665 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 2.278537e-02 | 1.642 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 2.246878e-02 | 1.648 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 2.016289e-02 | 1.695 |
| R-HSA-6784531 | tRNA processing in the nucleus | 2.017076e-02 | 1.695 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 2.049942e-02 | 1.688 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 2.184832e-02 | 1.661 |
| R-HSA-112040 | G-protein mediated events | 2.281962e-02 | 1.642 |
| R-HSA-447115 | Interleukin-12 family signaling | 2.329435e-02 | 1.633 |
| R-HSA-191859 | snRNP Assembly | 2.336412e-02 | 1.631 |
| R-HSA-194441 | Metabolism of non-coding RNA | 2.336412e-02 | 1.631 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 2.361233e-02 | 1.627 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 2.555514e-02 | 1.593 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 2.567531e-02 | 1.590 |
| R-HSA-69206 | G1/S Transition | 2.572772e-02 | 1.590 |
| R-HSA-69306 | DNA Replication | 2.598550e-02 | 1.585 |
| R-HSA-1500620 | Meiosis | 2.677318e-02 | 1.572 |
| R-HSA-1227986 | Signaling by ERBB2 | 2.677432e-02 | 1.572 |
| R-HSA-421270 | Cell-cell junction organization | 2.686016e-02 | 1.571 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 2.723896e-02 | 1.565 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 2.723896e-02 | 1.565 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 2.741308e-02 | 1.562 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 3.012528e-02 | 1.521 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 3.187666e-02 | 1.497 |
| R-HSA-426486 | Small interfering RNA (siRNA) biogenesis | 3.187666e-02 | 1.497 |
| R-HSA-199920 | CREB phosphorylation | 3.187666e-02 | 1.497 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 3.348446e-02 | 1.475 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 3.348446e-02 | 1.475 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 3.348446e-02 | 1.475 |
| R-HSA-171306 | Packaging Of Telomere Ends | 2.943603e-02 | 1.531 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 3.189169e-02 | 1.496 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 3.142520e-02 | 1.503 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 3.054982e-02 | 1.515 |
| R-HSA-4086400 | PCP/CE pathway | 3.160589e-02 | 1.500 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 2.950681e-02 | 1.530 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 2.950681e-02 | 1.530 |
| R-HSA-9609690 | HCMV Early Events | 3.385881e-02 | 1.470 |
| R-HSA-2682334 | EPH-Ephrin signaling | 2.827742e-02 | 1.549 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 3.242169e-02 | 1.489 |
| R-HSA-69560 | Transcriptional activation of p53 responsive genes | 3.012528e-02 | 1.521 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 | 3.012528e-02 | 1.521 |
| R-HSA-73864 | RNA Polymerase I Transcription | 3.160589e-02 | 1.500 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 3.128761e-02 | 1.505 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 3.243628e-02 | 1.489 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 3.155141e-02 | 1.501 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 2.943603e-02 | 1.531 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 3.219686e-02 | 1.492 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 3.160589e-02 | 1.500 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 3.421265e-02 | 1.466 |
| R-HSA-8863678 | Neurodegenerative Diseases | 3.421265e-02 | 1.466 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 3.620062e-02 | 1.441 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 3.649660e-02 | 1.438 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 3.694357e-02 | 1.432 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 3.720459e-02 | 1.429 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 3.720459e-02 | 1.429 |
| R-HSA-3928664 | Ephrin signaling | 3.720459e-02 | 1.429 |
| R-HSA-163615 | PKA activation | 3.720459e-02 | 1.429 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 3.720459e-02 | 1.429 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 3.720459e-02 | 1.429 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 3.737290e-02 | 1.427 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 3.737290e-02 | 1.427 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 3.790541e-02 | 1.421 |
| R-HSA-9617828 | FOXO-mediated transcription of cell cycle genes | 3.980083e-02 | 1.400 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 3.980083e-02 | 1.400 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 4.070097e-02 | 1.390 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 4.177720e-02 | 1.379 |
| R-HSA-912446 | Meiotic recombination | 4.177720e-02 | 1.379 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 4.240078e-02 | 1.373 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 4.240078e-02 | 1.373 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 4.255931e-02 | 1.371 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 4.293737e-02 | 1.367 |
| R-HSA-9710421 | Defective pyroptosis | 4.294891e-02 | 1.367 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 4.298699e-02 | 1.367 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 4.320188e-02 | 1.364 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 4.320188e-02 | 1.364 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 4.320188e-02 | 1.364 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 4.336219e-02 | 1.363 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 4.336219e-02 | 1.363 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 4.336219e-02 | 1.363 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 4.336219e-02 | 1.363 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 4.336219e-02 | 1.363 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 4.336219e-02 | 1.363 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 4.336219e-02 | 1.363 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 4.336219e-02 | 1.363 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 4.336219e-02 | 1.363 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 4.336219e-02 | 1.363 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 4.336219e-02 | 1.363 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 4.347467e-02 | 1.362 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 4.347467e-02 | 1.362 |
| R-HSA-3134963 | DEx/H-box helicases activate type I IFN and inflammatory cytokines production | 4.818313e-02 | 1.317 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 4.635455e-02 | 1.334 |
| R-HSA-114516 | Disinhibition of SNARE formation | 4.635455e-02 | 1.334 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 4.942733e-02 | 1.306 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 4.942733e-02 | 1.306 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 5.055567e-02 | 1.296 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 5.007387e-02 | 1.300 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 4.939096e-02 | 1.306 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 4.654036e-02 | 1.332 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 5.395197e-02 | 1.268 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 5.387373e-02 | 1.269 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 4.587891e-02 | 1.338 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 5.055567e-02 | 1.296 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 4.939096e-02 | 1.306 |
| R-HSA-8939211 | ESR-mediated signaling | 4.733719e-02 | 1.325 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 4.855396e-02 | 1.314 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 5.055567e-02 | 1.296 |
| R-HSA-202403 | TCR signaling | 5.462303e-02 | 1.263 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 5.387373e-02 | 1.269 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 5.132080e-02 | 1.290 |
| R-HSA-157118 | Signaling by NOTCH | 5.642037e-02 | 1.249 |
| R-HSA-75893 | TNF signaling | 4.654036e-02 | 1.332 |
| R-HSA-68949 | Orc1 removal from chromatin | 4.758814e-02 | 1.323 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 5.253637e-02 | 1.280 |
| R-HSA-442720 | CREB1 phosphorylation through the activation of Adenylate Cyclase | 4.942733e-02 | 1.306 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 4.587891e-02 | 1.338 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 4.877579e-02 | 1.312 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 5.632043e-02 | 1.249 |
| R-HSA-447038 | NrCAM interactions | 4.818313e-02 | 1.317 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 4.848733e-02 | 1.314 |
| R-HSA-9008059 | Interleukin-37 signaling | 5.055567e-02 | 1.296 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 5.648201e-02 | 1.248 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 5.648201e-02 | 1.248 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 5.661089e-02 | 1.247 |
| R-HSA-6807004 | Negative regulation of MET activity | 5.686182e-02 | 1.245 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 5.686182e-02 | 1.245 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 5.686182e-02 | 1.245 |
| R-HSA-373753 | Nephrin family interactions | 5.686182e-02 | 1.245 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 5.756802e-02 | 1.240 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 5.756802e-02 | 1.240 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 5.756802e-02 | 1.240 |
| R-HSA-9022534 | Loss of MECP2 binding ability to 5hmC-DNA | 5.773425e-02 | 1.239 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 5.912471e-02 | 1.228 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 5.912471e-02 | 1.228 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 5.912471e-02 | 1.228 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 5.929016e-02 | 1.227 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 5.929016e-02 | 1.227 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 5.943845e-02 | 1.226 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 6.295216e-02 | 1.201 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 6.295216e-02 | 1.201 |
| R-HSA-391160 | Signal regulatory protein family interactions | 6.295216e-02 | 1.201 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 6.387424e-02 | 1.195 |
| R-HSA-444257 | RSK activation | 6.416820e-02 | 1.193 |
| R-HSA-196025 | Formation of annular gap junctions | 6.416820e-02 | 1.193 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 6.416820e-02 | 1.193 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 6.416820e-02 | 1.193 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 6.424499e-02 | 1.192 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 6.643237e-02 | 1.178 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 6.643911e-02 | 1.178 |
| R-HSA-9827857 | Specification of primordial germ cells | 6.673637e-02 | 1.176 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 6.719935e-02 | 1.173 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 6.839717e-02 | 1.165 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 6.841672e-02 | 1.165 |
| R-HSA-1280218 | Adaptive Immune System | 6.869522e-02 | 1.163 |
| R-HSA-111931 | PKA-mediated phosphorylation of CREB | 6.880992e-02 | 1.162 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 6.899679e-02 | 1.161 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 6.930213e-02 | 1.159 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 6.930213e-02 | 1.159 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 6.971171e-02 | 1.157 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 6.971171e-02 | 1.157 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 7.105120e-02 | 1.148 |
| R-HSA-8935964 | RUNX1 regulates expression of components of tight junctions | 7.105120e-02 | 1.148 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 7.206728e-02 | 1.142 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 7.256610e-02 | 1.139 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 7.256610e-02 | 1.139 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 7.336149e-02 | 1.135 |
| R-HSA-162592 | Integration of provirus | 7.336149e-02 | 1.135 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 7.342510e-02 | 1.134 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 7.379046e-02 | 1.132 |
| R-HSA-8875513 | MET interacts with TNS proteins | 7.379046e-02 | 1.132 |
| R-HSA-9022538 | Loss of MECP2 binding ability to 5mC-DNA | 7.379046e-02 | 1.132 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 7.588767e-02 | 1.120 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 7.675018e-02 | 1.115 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 7.761358e-02 | 1.110 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 7.761358e-02 | 1.110 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 7.761358e-02 | 1.110 |
| R-HSA-193639 | p75NTR signals via NF-kB | 7.852008e-02 | 1.105 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 7.852008e-02 | 1.105 |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment | 7.852008e-02 | 1.105 |
| R-HSA-418885 | DCC mediated attractive signaling | 7.852008e-02 | 1.105 |
| R-HSA-171007 | p38MAPK events | 7.852008e-02 | 1.105 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 7.852008e-02 | 1.105 |
| R-HSA-1234174 | Cellular response to hypoxia | 7.918057e-02 | 1.101 |
| R-HSA-72187 | mRNA 3'-end processing | 7.919517e-02 | 1.101 |
| R-HSA-6794361 | Neurexins and neuroligins | 7.919517e-02 | 1.101 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 7.944073e-02 | 1.100 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 8.016961e-02 | 1.096 |
| R-HSA-156711 | Polo-like kinase mediated events | 8.117525e-02 | 1.091 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 8.185934e-02 | 1.087 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 8.218277e-02 | 1.085 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 8.218277e-02 | 1.085 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 8.219693e-02 | 1.085 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 8.221526e-02 | 1.085 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 8.221526e-02 | 1.085 |
| R-HSA-69478 | G2/M DNA replication checkpoint | 9.850029e-02 | 1.007 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 8.530440e-02 | 1.069 |
| R-HSA-9613354 | Lipophagy | 8.530440e-02 | 1.069 |
| R-HSA-190873 | Gap junction degradation | 8.530440e-02 | 1.069 |
| R-HSA-164843 | 2-LTR circle formation | 1.096348e-01 | 0.960 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 9.264257e-02 | 1.033 |
| R-HSA-350054 | Notch-HLH transcription pathway | 9.708513e-02 | 1.013 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 9.418791e-02 | 1.026 |
| R-HSA-4641257 | Degradation of AXIN | 8.967282e-02 | 1.047 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 8.848407e-02 | 1.053 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 9.276597e-02 | 1.033 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 9.754526e-02 | 1.011 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 9.593411e-02 | 1.018 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 1.063447e-01 | 0.973 |
| R-HSA-202424 | Downstream TCR signaling | 1.100569e-01 | 0.958 |
| R-HSA-73886 | Chromosome Maintenance | 1.043913e-01 | 0.981 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 8.967282e-02 | 1.047 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.076402e-01 | 0.968 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 8.967282e-02 | 1.047 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 9.837299e-02 | 1.007 |
| R-HSA-9007101 | Rab regulation of trafficking | 1.089592e-01 | 0.963 |
| R-HSA-877312 | Regulation of IFNG signaling | 9.264257e-02 | 1.033 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 8.713859e-02 | 1.060 |
| R-HSA-5689603 | UCH proteinases | 9.731007e-02 | 1.012 |
| R-HSA-392517 | Rap1 signalling | 9.732081e-02 | 1.012 |
| R-HSA-9006936 | Signaling by TGFB family members | 8.372846e-02 | 1.077 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 9.645567e-02 | 1.016 |
| R-HSA-9707616 | Heme signaling | 9.103701e-02 | 1.041 |
| R-HSA-9839373 | Signaling by TGFBR3 | 1.063447e-01 | 0.973 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 1.096348e-01 | 0.960 |
| R-HSA-2586552 | Signaling by Leptin | 1.096348e-01 | 0.960 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 1.104552e-01 | 0.957 |
| R-HSA-176974 | Unwinding of DNA | 8.530440e-02 | 1.069 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 1.096348e-01 | 0.960 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 9.612826e-02 | 1.017 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 1.049603e-01 | 0.979 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 1.104914e-01 | 0.957 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 1.107716e-01 | 0.956 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 1.107716e-01 | 0.956 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 1.109601e-01 | 0.955 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 1.112759e-01 | 0.954 |
| R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death | 1.112759e-01 | 0.954 |
| R-HSA-205025 | NADE modulates death signalling | 1.112759e-01 | 0.954 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 1.112759e-01 | 0.954 |
| R-HSA-165181 | Inhibition of TSC complex formation by PKB | 1.112759e-01 | 0.954 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 1.112759e-01 | 0.954 |
| R-HSA-2644607 | Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling | 1.112759e-01 | 0.954 |
| R-HSA-2644605 | FBXW7 Mutants and NOTCH1 in Cancer | 1.112759e-01 | 0.954 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 1.112759e-01 | 0.954 |
| R-HSA-9705677 | SARS-CoV-2 targets PDZ proteins in cell-cell junction | 1.112759e-01 | 0.954 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 1.134058e-01 | 0.945 |
| R-HSA-3000170 | Syndecan interactions | 1.134058e-01 | 0.945 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 1.143791e-01 | 0.942 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 1.143791e-01 | 0.942 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 1.143791e-01 | 0.942 |
| R-HSA-69541 | Stabilization of p53 | 1.146458e-01 | 0.941 |
| R-HSA-190704 | Oligomerization of connexins into connexons | 1.148492e-01 | 0.940 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 1.148492e-01 | 0.940 |
| R-HSA-190827 | Transport of connexins along the secretory pathway | 1.148492e-01 | 0.940 |
| R-HSA-5632928 | Defective Mismatch Repair Associated With MSH2 | 1.148492e-01 | 0.940 |
| R-HSA-5603027 | IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... | 1.148492e-01 | 0.940 |
| R-HSA-5602636 | IKBKB deficiency causes SCID | 1.148492e-01 | 0.940 |
| R-HSA-352238 | Breakdown of the nuclear lamina | 1.148492e-01 | 0.940 |
| R-HSA-9823730 | Formation of definitive endoderm | 1.151473e-01 | 0.939 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 1.156944e-01 | 0.937 |
| R-HSA-77595 | Processing of Intronless Pre-mRNAs | 1.157321e-01 | 0.937 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 1.157321e-01 | 0.937 |
| R-HSA-9679506 | SARS-CoV Infections | 1.159138e-01 | 0.936 |
| R-HSA-1474165 | Reproduction | 1.168471e-01 | 0.932 |
| R-HSA-168255 | Influenza Infection | 1.183858e-01 | 0.927 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 1.184282e-01 | 0.927 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 1.188814e-01 | 0.925 |
| R-HSA-169911 | Regulation of Apoptosis | 1.188814e-01 | 0.925 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 1.188814e-01 | 0.925 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1.203883e-01 | 0.919 |
| R-HSA-9013694 | Signaling by NOTCH4 | 1.209622e-01 | 0.917 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 1.227653e-01 | 0.911 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 1.231076e-01 | 0.910 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 1.231076e-01 | 0.910 |
| R-HSA-8854214 | TBC/RABGAPs | 1.233803e-01 | 0.909 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 1.257055e-01 | 0.901 |
| R-HSA-1483249 | Inositol phosphate metabolism | 1.271978e-01 | 0.896 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 1.283597e-01 | 0.892 |
| R-HSA-9702506 | Drug resistance of FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9700649 | Drug resistance of ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669937 | Drug resistance of KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9674415 | Drug resistance of PDGFR mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669921 | KIT mutants bind TKIs | 1.753755e-01 | 0.756 |
| R-HSA-9702509 | FLT3 mutants bind TKIs | 1.753755e-01 | 0.756 |
| R-HSA-9674428 | PDGFR mutants bind TKIs | 1.753755e-01 | 0.756 |
| R-HSA-9717329 | lorlatinib-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9717264 | ASP-3026-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702614 | ponatinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702596 | lestaurtinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702636 | tandutinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669934 | Sunitinib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9717326 | crizotinib-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9674401 | Sunitinib-resistant PDGFR mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669936 | Sorafenib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9717301 | NVP-TAE684-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702998 | linifanib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702577 | semaxanib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9674396 | Imatinib-resistant PDGFR mutants | 1.753755e-01 | 0.756 |
| R-HSA-9717323 | ceritinib-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669926 | Nilotinib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702581 | crenolanib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702605 | pexidartinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702569 | KW2449-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-5687868 | Defective SFTPA2 causes IPF | 1.753755e-01 | 0.756 |
| R-HSA-9702620 | quizartinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9717316 | alectinib-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669924 | Masitinib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669917 | Imatinib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702632 | sunitinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669929 | Regorafenib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702624 | sorafenib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9674404 | Sorafenib-resistant PDGFR mutants | 1.753755e-01 | 0.756 |
| R-HSA-9702590 | gilteritinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9669914 | Dasatinib-resistant KIT mutants | 1.753755e-01 | 0.756 |
| R-HSA-9703009 | tamatinib-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9661070 | Defective translocation of RB1 mutants to the nucleus | 1.753755e-01 | 0.756 |
| R-HSA-9702600 | midostaurin-resistant FLT3 mutants | 1.753755e-01 | 0.756 |
| R-HSA-9717319 | brigatinib-resistant ALK mutants | 1.753755e-01 | 0.756 |
| R-HSA-5467333 | APC truncation mutants are not K63 polyubiquitinated | 1.753755e-01 | 0.756 |
| R-HSA-9674403 | Regorafenib-resistant PDGFR mutants | 1.753755e-01 | 0.756 |
| R-HSA-211736 | Stimulation of the cell death response by PAK-2p34 | 1.809149e-01 | 0.743 |
| R-HSA-8985801 | Regulation of cortical dendrite branching | 1.809149e-01 | 0.743 |
| R-HSA-3828062 | Glycogen storage disease type 0 (muscle GYS1) | 1.809149e-01 | 0.743 |
| R-HSA-3814836 | Glycogen storage disease type XV (GYG1) | 1.809149e-01 | 0.743 |
| R-HSA-74713 | IRS activation | 1.544599e-01 | 0.811 |
| R-HSA-68911 | G2 Phase | 1.544599e-01 | 0.811 |
| R-HSA-9022535 | Loss of phosphorylation of MECP2 at T308 | 1.544599e-01 | 0.811 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 1.652932e-01 | 0.782 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 1.652932e-01 | 0.782 |
| R-HSA-1433559 | Regulation of KIT signaling | 1.384374e-01 | 0.859 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 1.384374e-01 | 0.859 |
| R-HSA-209560 | NF-kB is activated and signals survival | 1.668956e-01 | 0.778 |
| R-HSA-428540 | Activation of RAC1 | 1.668956e-01 | 0.778 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 1.646339e-01 | 0.783 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 1.311433e-01 | 0.882 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 1.556040e-01 | 0.808 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 | 1.855148e-01 | 0.732 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 1.447360e-01 | 0.839 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 1.447360e-01 | 0.839 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 1.780534e-01 | 0.749 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 1.633984e-01 | 0.787 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 1.285099e-01 | 0.891 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 1.564079e-01 | 0.806 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 1.496953e-01 | 0.825 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 1.922319e-01 | 0.716 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.922319e-01 | 0.716 |
| R-HSA-9607240 | FLT3 Signaling | 1.432716e-01 | 0.844 |
| R-HSA-389356 | Co-stimulation by CD28 | 1.312845e-01 | 0.882 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 1.589055e-01 | 0.799 |
| R-HSA-9764561 | Regulation of CDH1 Function | 1.323661e-01 | 0.878 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.670637e-01 | 0.777 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.670637e-01 | 0.777 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.670637e-01 | 0.777 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 1.670637e-01 | 0.777 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 1.831788e-01 | 0.737 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 1.721990e-01 | 0.764 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 1.900994e-01 | 0.721 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 1.900994e-01 | 0.721 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 1.900994e-01 | 0.721 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 1.320884e-01 | 0.879 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 1.665253e-01 | 0.779 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 1.688351e-01 | 0.773 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 1.765987e-01 | 0.753 |
| R-HSA-6798695 | Neutrophil degranulation | 1.616846e-01 | 0.791 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 1.669363e-01 | 0.777 |
| R-HSA-6806834 | Signaling by MET | 1.917591e-01 | 0.717 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 1.346013e-01 | 0.871 |
| R-HSA-1433557 | Signaling by SCF-KIT | 1.926513e-01 | 0.715 |
| R-HSA-167044 | Signalling to RAS | 1.346013e-01 | 0.871 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 1.311433e-01 | 0.882 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 1.301147e-01 | 0.886 |
| R-HSA-8849932 | Synaptic adhesion-like molecules | 1.605587e-01 | 0.794 |
| R-HSA-9907900 | Proteasome assembly | 1.371367e-01 | 0.863 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 1.384625e-01 | 0.859 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 1.384792e-01 | 0.859 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 1.706359e-01 | 0.768 |
| R-HSA-5205647 | Mitophagy | 1.746037e-01 | 0.758 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 1.926513e-01 | 0.715 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 1.471042e-01 | 0.832 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 1.513609e-01 | 0.820 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 1.668956e-01 | 0.778 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 1.582869e-01 | 0.801 |
| R-HSA-156902 | Peptide chain elongation | 1.866531e-01 | 0.729 |
| R-HSA-111885 | Opioid Signalling | 1.765987e-01 | 0.753 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 1.746037e-01 | 0.758 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.670637e-01 | 0.777 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 1.753787e-01 | 0.756 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 1.519184e-01 | 0.818 |
| R-HSA-69239 | Synthesis of DNA | 1.688351e-01 | 0.773 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 1.922319e-01 | 0.716 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 1.917591e-01 | 0.717 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 1.851555e-01 | 0.732 |
| R-HSA-73894 | DNA Repair | 1.382632e-01 | 0.859 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 1.646339e-01 | 0.783 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 1.598262e-01 | 0.796 |
| R-HSA-180024 | DARPP-32 events | 1.447360e-01 | 0.839 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 1.806227e-01 | 0.743 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 1.392268e-01 | 0.856 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 1.384792e-01 | 0.859 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 1.447360e-01 | 0.839 |
| R-HSA-449836 | Other interleukin signaling | 1.855148e-01 | 0.732 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 1.392268e-01 | 0.856 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 1.496953e-01 | 0.825 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 1.867181e-01 | 0.729 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 1.590443e-01 | 0.798 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 1.430677e-01 | 0.844 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 1.867181e-01 | 0.729 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 1.384792e-01 | 0.859 |
| R-HSA-9825895 | Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... | 1.652932e-01 | 0.782 |
| R-HSA-9824446 | Viral Infection Pathways | 1.306448e-01 | 0.884 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 1.372484e-01 | 0.862 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 1.842561e-01 | 0.735 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 1.285099e-01 | 0.891 |
| R-HSA-110331 | Cleavage of the damaged purine | 1.496953e-01 | 0.825 |
| R-HSA-73927 | Depurination | 1.665280e-01 | 0.779 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 1.564079e-01 | 0.806 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 1.753787e-01 | 0.756 |
| R-HSA-73928 | Depyrimidination | 1.753787e-01 | 0.756 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 1.927446e-01 | 0.715 |
| R-HSA-187687 | Signalling to ERKs | 1.937568e-01 | 0.713 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 1.968463e-01 | 0.706 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 1.991615e-01 | 0.701 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 1.991615e-01 | 0.701 |
| R-HSA-9697154 | Disorders of Nervous System Development | 1.991615e-01 | 0.701 |
| R-HSA-9005895 | Pervasive developmental disorders | 1.991615e-01 | 0.701 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 1.991615e-01 | 0.701 |
| R-HSA-9842663 | Signaling by LTK | 1.991615e-01 | 0.701 |
| R-HSA-8983711 | OAS antiviral response | 1.991615e-01 | 0.701 |
| R-HSA-446652 | Interleukin-1 family signaling | 2.009173e-01 | 0.697 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 2.015465e-01 | 0.696 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 2.018280e-01 | 0.695 |
| R-HSA-176417 | Phosphorylation of Emi1 | 2.018835e-01 | 0.695 |
| R-HSA-5576894 | Phase 1 - inactivation of fast Na+ channels | 2.018835e-01 | 0.695 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 2.018835e-01 | 0.695 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 2.018835e-01 | 0.695 |
| R-HSA-163358 | PKA-mediated phosphorylation of key metabolic factors | 2.018835e-01 | 0.695 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 2.028280e-01 | 0.693 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 2.034234e-01 | 0.692 |
| R-HSA-428543 | Inactivation of CDC42 and RAC1 | 2.034234e-01 | 0.692 |
| R-HSA-201688 | WNT mediated activation of DVL | 2.034234e-01 | 0.692 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 2.034234e-01 | 0.692 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 2.034234e-01 | 0.692 |
| R-HSA-69190 | DNA strand elongation | 2.039530e-01 | 0.690 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 2.065195e-01 | 0.685 |
| R-HSA-9711123 | Cellular response to chemical stress | 2.072908e-01 | 0.683 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 2.089404e-01 | 0.680 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 2.113386e-01 | 0.675 |
| R-HSA-9682385 | FLT3 signaling in disease | 2.138006e-01 | 0.670 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 2.138006e-01 | 0.670 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 2.149299e-01 | 0.668 |
| R-HSA-9766229 | Degradation of CDH1 | 2.175289e-01 | 0.662 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 3.200026e-01 | 0.495 |
| R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 3.200026e-01 | 0.495 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 3.200026e-01 | 0.495 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 3.200026e-01 | 0.495 |
| R-HSA-9734091 | Drug-mediated inhibition of MET activation | 3.200026e-01 | 0.495 |
| R-HSA-5632987 | Defective Mismatch Repair Associated With PMS2 | 3.200026e-01 | 0.495 |
| R-HSA-5602566 | TICAM1 deficiency - HSE | 3.200026e-01 | 0.495 |
| R-HSA-9663199 | Defective DNA double strand break response due to BRCA1 loss of function | 3.200026e-01 | 0.495 |
| R-HSA-9709275 | Impaired BRCA2 translocation to the nucleus | 3.200026e-01 | 0.495 |
| R-HSA-9699150 | Defective DNA double strand break response due to BARD1 loss of function | 3.200026e-01 | 0.495 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 3.200026e-01 | 0.495 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 3.200026e-01 | 0.495 |
| R-HSA-5659996 | RPIA deficiency: failed conversion of R5P to RU5P | 3.200026e-01 | 0.495 |
| R-HSA-5632968 | Defective Mismatch Repair Associated With MSH6 | 3.200026e-01 | 0.495 |
| R-HSA-6791461 | RPIA deficiency: failed conversion of RU5P to R5P | 3.200026e-01 | 0.495 |
| R-HSA-9036092 | Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus... | 3.200026e-01 | 0.495 |
| R-HSA-5632927 | Defective Mismatch Repair Associated With MSH3 | 3.200026e-01 | 0.495 |
| R-HSA-5545483 | Defective Mismatch Repair Associated With MLH1 | 3.200026e-01 | 0.495 |
| R-HSA-9763198 | Impaired BRCA2 binding to SEM1 (DSS1) | 3.200026e-01 | 0.495 |
| R-HSA-8875791 | MET activates STAT3 | 2.510373e-01 | 0.600 |
| R-HSA-209563 | Axonal growth stimulation | 2.510373e-01 | 0.600 |
| R-HSA-9673766 | Signaling by cytosolic PDGFRA and PDGFRB fusion proteins | 2.510373e-01 | 0.600 |
| R-HSA-8865999 | MET activates PTPN11 | 2.510373e-01 | 0.600 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 2.521274e-01 | 0.598 |
| R-HSA-9645135 | STAT5 Activation | 2.521274e-01 | 0.598 |
| R-HSA-191650 | Regulation of gap junction activity | 3.217629e-01 | 0.492 |
| R-HSA-9022927 | MECP2 regulates transcription of genes involved in GABA signaling | 3.217629e-01 | 0.492 |
| R-HSA-8941333 | RUNX2 regulates genes involved in differentiation of myeloid cells | 3.217629e-01 | 0.492 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 3.217629e-01 | 0.492 |
| R-HSA-5083630 | Defective LFNG causes SCDO3 | 3.217629e-01 | 0.492 |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... | 3.217629e-01 | 0.492 |
| R-HSA-9680187 | Signaling by extracellular domain mutants of KIT | 4.392710e-01 | 0.357 |
| R-HSA-205017 | NFG and proNGF binds to p75NTR | 4.392710e-01 | 0.357 |
| R-HSA-176034 | Interactions of Tat with host cellular proteins | 4.392710e-01 | 0.357 |
| R-HSA-9669935 | Signaling by juxtamembrane domain KIT mutants | 4.392710e-01 | 0.357 |
| R-HSA-5545619 | XAV939 stabilizes AXIN | 4.392710e-01 | 0.357 |
| R-HSA-5339700 | Signaling by TCF7L2 mutants | 4.392710e-01 | 0.357 |
| R-HSA-3304347 | Loss of Function of SMAD4 in Cancer | 4.392710e-01 | 0.357 |
| R-HSA-5609977 | Defective GALE causes EDG | 4.392710e-01 | 0.357 |
| R-HSA-5619111 | Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1) | 4.392710e-01 | 0.357 |
| R-HSA-6791462 | TALDO1 deficiency: failed conversion of Fru(6)P, E4P to SH7P, GA3P | 4.392710e-01 | 0.357 |
| R-HSA-9915355 | Beta-ketothiolase deficiency | 4.392710e-01 | 0.357 |
| R-HSA-3311021 | SMAD4 MH2 Domain Mutants in Cancer | 4.392710e-01 | 0.357 |
| R-HSA-5609974 | Defective PGM1 causes PGM1-CDG | 4.392710e-01 | 0.357 |
| R-HSA-5674404 | PTEN Loss of Function in Cancer | 4.392710e-01 | 0.357 |
| R-HSA-5602571 | TRAF3 deficiency - HSE | 4.392710e-01 | 0.357 |
| R-HSA-9669933 | Signaling by kinase domain mutants of KIT | 4.392710e-01 | 0.357 |
| R-HSA-6791055 | TALDO1 deficiency: failed conversion of SH7P, GA3P to Fru(6)P, E4P | 4.392710e-01 | 0.357 |
| R-HSA-5619109 | Defective SLC6A2 causes orthostatic intolerance (OI) | 4.392710e-01 | 0.357 |
| R-HSA-4085023 | Defective GFPT1 causes CMSTA1 | 4.392710e-01 | 0.357 |
| R-HSA-3315487 | SMAD2/3 MH2 Domain Mutants in Cancer | 4.392710e-01 | 0.357 |
| R-HSA-5619054 | Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalit... | 4.392710e-01 | 0.357 |
| R-HSA-3359485 | Defective CD320 causes MMATC | 4.392710e-01 | 0.357 |
| R-HSA-74749 | Signal attenuation | 2.438092e-01 | 0.613 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 2.438092e-01 | 0.613 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 2.438092e-01 | 0.613 |
| R-HSA-451308 | Activation of Ca-permeable Kainate Receptor | 2.438092e-01 | 0.613 |
| R-HSA-447041 | CHL1 interactions | 3.038952e-01 | 0.517 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 3.038952e-01 | 0.517 |
| R-HSA-2562578 | TRIF-mediated programmed cell death | 3.038952e-01 | 0.517 |
| R-HSA-9632974 | NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis | 3.038952e-01 | 0.517 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 3.038952e-01 | 0.517 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 2.333332e-01 | 0.632 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 2.333332e-01 | 0.632 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 2.225148e-01 | 0.653 |
| R-HSA-4420332 | Defective B3GALT6 causes EDSP2 and SEMDJL1 | 2.225148e-01 | 0.653 |
| R-HSA-3560783 | Defective B4GALT7 causes EDS, progeroid type | 2.225148e-01 | 0.653 |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 2.857681e-01 | 0.544 |
| R-HSA-8941284 | RUNX2 regulates chondrocyte maturation | 3.907240e-01 | 0.408 |
| R-HSA-165158 | Activation of AKT2 | 3.907240e-01 | 0.408 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 3.907240e-01 | 0.408 |
| R-HSA-9673768 | Signaling by membrane-tethered fusions of PDGFRA or PDGFRB | 3.907240e-01 | 0.408 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 3.907240e-01 | 0.408 |
| R-HSA-9706377 | FLT3 signaling by CBL mutants | 3.907240e-01 | 0.408 |
| R-HSA-3560801 | Defective B3GAT3 causes JDSSDHD | 2.536690e-01 | 0.596 |
| R-HSA-8875656 | MET receptor recycling | 3.560561e-01 | 0.448 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 3.560561e-01 | 0.448 |
| R-HSA-3785653 | Myoclonic epilepsy of Lafora | 3.560561e-01 | 0.448 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 3.560561e-01 | 0.448 |
| R-HSA-210991 | Basigin interactions | 2.396545e-01 | 0.620 |
| R-HSA-429947 | Deadenylation of mRNA | 2.267897e-01 | 0.644 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 3.286475e-01 | 0.483 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 3.057262e-01 | 0.515 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 2.859202e-01 | 0.544 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 2.859202e-01 | 0.544 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 2.684411e-01 | 0.571 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 2.684411e-01 | 0.571 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 2.684411e-01 | 0.571 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 2.386166e-01 | 0.622 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 2.482562e-01 | 0.605 |
| R-HSA-912631 | Regulation of signaling by CBL | 3.189786e-01 | 0.496 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 3.189786e-01 | 0.496 |
| R-HSA-9664420 | Killing mechanisms | 3.431202e-01 | 0.465 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 3.431202e-01 | 0.465 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 3.431202e-01 | 0.465 |
| R-HSA-2197563 | NOTCH2 intracellular domain regulates transcription | 3.718448e-01 | 0.430 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 3.718448e-01 | 0.430 |
| R-HSA-2428933 | SHC-related events triggered by IGF1R | 3.718448e-01 | 0.430 |
| R-HSA-69091 | Polymerase switching | 3.718448e-01 | 0.430 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 3.718448e-01 | 0.430 |
| R-HSA-9931530 | Phosphorylation and nuclear translocation of the CRY:PER:kinase complex | 3.718448e-01 | 0.430 |
| R-HSA-69109 | Leading Strand Synthesis | 3.718448e-01 | 0.430 |
| R-HSA-3656253 | Defective EXT1 causes exostoses 1, TRPS2 and CHDS | 3.718448e-01 | 0.430 |
| R-HSA-3656237 | Defective EXT2 causes exostoses 2 | 3.718448e-01 | 0.430 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 3.718448e-01 | 0.430 |
| R-HSA-9020958 | Interleukin-21 signaling | 4.076628e-01 | 0.390 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 4.076628e-01 | 0.390 |
| R-HSA-2465910 | MASTL Facilitates Mitotic Progression | 4.076628e-01 | 0.390 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 2.294030e-01 | 0.639 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 2.422620e-01 | 0.616 |
| R-HSA-167161 | HIV Transcription Initiation | 2.422620e-01 | 0.616 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 2.422620e-01 | 0.616 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 3.525582e-01 | 0.453 |
| R-HSA-9609523 | Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 3.525582e-01 | 0.453 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 3.525582e-01 | 0.453 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 3.525582e-01 | 0.453 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 3.525582e-01 | 0.453 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 3.525582e-01 | 0.453 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 3.525582e-01 | 0.453 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 3.807893e-01 | 0.419 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 3.807893e-01 | 0.419 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 3.807893e-01 | 0.419 |
| R-HSA-167172 | Transcription of the HIV genome | 2.221176e-01 | 0.653 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 2.687229e-01 | 0.571 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 2.842889e-01 | 0.546 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 4.148208e-01 | 0.382 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 4.148208e-01 | 0.382 |
| R-HSA-9634597 | GPER1 signaling | 2.891890e-01 | 0.539 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 3.863839e-01 | 0.413 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 3.863839e-01 | 0.413 |
| R-HSA-9006335 | Signaling by Erythropoietin | 3.638647e-01 | 0.439 |
| R-HSA-9615710 | Late endosomal microautophagy | 3.638647e-01 | 0.439 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 3.101021e-01 | 0.508 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 4.183751e-01 | 0.378 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 4.183751e-01 | 0.378 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 4.183751e-01 | 0.378 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 3.282962e-01 | 0.484 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 3.000984e-01 | 0.523 |
| R-HSA-2424491 | DAP12 signaling | 3.925699e-01 | 0.406 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 4.201960e-01 | 0.377 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 3.072821e-01 | 0.512 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 3.942710e-01 | 0.404 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 3.942710e-01 | 0.404 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 3.942710e-01 | 0.404 |
| R-HSA-3295583 | TRP channels | 4.210533e-01 | 0.376 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 3.244688e-01 | 0.489 |
| R-HSA-182971 | EGFR downregulation | 4.213243e-01 | 0.375 |
| R-HSA-9711097 | Cellular response to starvation | 3.209649e-01 | 0.494 |
| R-HSA-201556 | Signaling by ALK | 2.784973e-01 | 0.555 |
| R-HSA-5696398 | Nucleotide Excision Repair | 2.602263e-01 | 0.585 |
| R-HSA-8983432 | Interleukin-15 signaling | 3.718448e-01 | 0.430 |
| R-HSA-69236 | G1 Phase | 3.060852e-01 | 0.514 |
| R-HSA-69231 | Cyclin D associated events in G1 | 3.060852e-01 | 0.514 |
| R-HSA-186763 | Downstream signal transduction | 4.213243e-01 | 0.375 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 4.208506e-01 | 0.376 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 4.208506e-01 | 0.376 |
| R-HSA-177929 | Signaling by EGFR | 3.547269e-01 | 0.450 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 3.448750e-01 | 0.462 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 3.395036e-01 | 0.469 |
| R-HSA-68962 | Activation of the pre-replicative complex | 2.631691e-01 | 0.580 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 4.076628e-01 | 0.390 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 3.863839e-01 | 0.413 |
| R-HSA-418889 | Caspase activation via Dependence Receptors in the absence of ligand | 4.076628e-01 | 0.390 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 3.770406e-01 | 0.424 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 3.286475e-01 | 0.483 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 3.807893e-01 | 0.419 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 2.521274e-01 | 0.598 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 2.221850e-01 | 0.653 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 2.955210e-01 | 0.529 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 3.925699e-01 | 0.406 |
| R-HSA-157579 | Telomere Maintenance | 3.447724e-01 | 0.462 |
| R-HSA-451927 | Interleukin-2 family signaling | 3.012960e-01 | 0.521 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 2.884578e-01 | 0.540 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 3.057262e-01 | 0.515 |
| R-HSA-5674135 | MAP2K and MAPK activation | 2.422620e-01 | 0.616 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 2.629883e-01 | 0.580 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 3.591180e-01 | 0.445 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 3.407049e-01 | 0.468 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 3.807893e-01 | 0.419 |
| R-HSA-1236974 | ER-Phagosome pathway | 2.659418e-01 | 0.575 |
| R-HSA-381042 | PERK regulates gene expression | 4.212158e-01 | 0.375 |
| R-HSA-1592230 | Mitochondrial biogenesis | 3.178608e-01 | 0.498 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 3.907240e-01 | 0.408 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 2.684411e-01 | 0.571 |
| R-HSA-114604 | GPVI-mediated activation cascade | 3.199932e-01 | 0.495 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 3.407049e-01 | 0.468 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 3.700530e-01 | 0.432 |
| R-HSA-72764 | Eukaryotic Translation Termination | 3.134359e-01 | 0.504 |
| R-HSA-6783589 | Interleukin-6 family signaling | 2.267897e-01 | 0.644 |
| R-HSA-432142 | Platelet sensitization by LDL | 2.859202e-01 | 0.544 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 2.796607e-01 | 0.553 |
| R-HSA-448424 | Interleukin-17 signaling | 3.395036e-01 | 0.469 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 3.764316e-01 | 0.424 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 2.552213e-01 | 0.593 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 2.616480e-01 | 0.582 |
| R-HSA-165159 | MTOR signalling | 3.720818e-01 | 0.429 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 3.560561e-01 | 0.448 |
| R-HSA-399719 | Trafficking of AMPA receptors | 2.884578e-01 | 0.540 |
| R-HSA-450294 | MAP kinase activation | 2.636156e-01 | 0.579 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 2.606493e-01 | 0.584 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 3.020110e-01 | 0.520 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 4.213243e-01 | 0.375 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 3.481843e-01 | 0.458 |
| R-HSA-9020558 | Interleukin-2 signaling | 2.857681e-01 | 0.544 |
| R-HSA-1266695 | Interleukin-7 signaling | 3.900729e-01 | 0.409 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 3.508394e-01 | 0.455 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 2.805147e-01 | 0.552 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 3.598473e-01 | 0.444 |
| R-HSA-4086398 | Ca2+ pathway | 3.051948e-01 | 0.515 |
| R-HSA-8985947 | Interleukin-9 signaling | 3.560561e-01 | 0.448 |
| R-HSA-74160 | Gene expression (Transcription) | 3.140694e-01 | 0.503 |
| R-HSA-9609646 | HCMV Infection | 2.207075e-01 | 0.656 |
| R-HSA-110381 | Resolution of AP sites via the single-nucleotide replacement pathway | 3.907240e-01 | 0.408 |
| R-HSA-111464 | SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | 3.907240e-01 | 0.408 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 2.221850e-01 | 0.653 |
| R-HSA-442380 | Zinc influx into cells by the SLC39 gene family | 4.076628e-01 | 0.390 |
| R-HSA-2025928 | Calcineurin activates NFAT | 4.076628e-01 | 0.390 |
| R-HSA-449147 | Signaling by Interleukins | 3.548518e-01 | 0.450 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 2.256826e-01 | 0.647 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 4.210533e-01 | 0.376 |
| R-HSA-166520 | Signaling by NTRKs | 2.616480e-01 | 0.582 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 3.395036e-01 | 0.469 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 2.980908e-01 | 0.526 |
| R-HSA-8984722 | Interleukin-35 Signalling | 3.718448e-01 | 0.430 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 2.842889e-01 | 0.546 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 2.386166e-01 | 0.622 |
| R-HSA-9020956 | Interleukin-27 signaling | 2.438092e-01 | 0.613 |
| R-HSA-9020702 | Interleukin-1 signaling | 3.297814e-01 | 0.482 |
| R-HSA-373752 | Netrin-1 signaling | 3.060852e-01 | 0.514 |
| R-HSA-77042 | Formation of editosomes by ADAR proteins | 3.200026e-01 | 0.495 |
| R-HSA-169131 | Inhibition of PKR | 3.200026e-01 | 0.495 |
| R-HSA-5660489 | MTF1 activates gene expression | 3.217629e-01 | 0.492 |
| R-HSA-211163 | AKT-mediated inactivation of FOXO1A | 3.217629e-01 | 0.492 |
| R-HSA-9839397 | TGFBR3 regulates FGF2 signaling | 4.392710e-01 | 0.357 |
| R-HSA-168315 | Inhibition of Host mRNA Processing and RNA Silencing | 4.392710e-01 | 0.357 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 3.038952e-01 | 0.517 |
| R-HSA-451306 | Ionotropic activity of kainate receptors | 2.857681e-01 | 0.544 |
| R-HSA-111463 | SMAC (DIABLO) binds to IAPs | 3.907240e-01 | 0.408 |
| R-HSA-8866376 | Reelin signalling pathway | 3.907240e-01 | 0.408 |
| R-HSA-9818025 | NFE2L2 regulating TCA cycle genes | 3.907240e-01 | 0.408 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 3.560561e-01 | 0.448 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 2.859202e-01 | 0.544 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 2.221850e-01 | 0.653 |
| R-HSA-9603798 | Class I peroxisomal membrane protein import | 3.431202e-01 | 0.465 |
| R-HSA-9634600 | Regulation of glycolysis by fructose 2,6-bisphosphate metabolism | 3.431202e-01 | 0.465 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 3.283878e-01 | 0.484 |
| R-HSA-5620924 | Intraflagellar transport | 3.965904e-01 | 0.402 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 3.740793e-01 | 0.427 |
| R-HSA-9824272 | Somitogenesis | 2.294030e-01 | 0.639 |
| R-HSA-2559585 | Oncogene Induced Senescence | 2.955210e-01 | 0.529 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 2.221850e-01 | 0.653 |
| R-HSA-9675135 | Diseases of DNA repair | 3.508394e-01 | 0.455 |
| R-HSA-198753 | ERK/MAPK targets | 3.863839e-01 | 0.413 |
| R-HSA-2408557 | Selenocysteine synthesis | 4.093136e-01 | 0.388 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 3.189786e-01 | 0.496 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 2.333332e-01 | 0.632 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 4.076628e-01 | 0.390 |
| R-HSA-448706 | Interleukin-1 processing | 4.076628e-01 | 0.390 |
| R-HSA-1483255 | PI Metabolism | 4.256715e-01 | 0.371 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 3.282962e-01 | 0.484 |
| R-HSA-9679191 | Potential therapeutics for SARS | 3.457945e-01 | 0.461 |
| R-HSA-5632684 | Hedgehog 'on' state | 2.707903e-01 | 0.567 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 3.199932e-01 | 0.495 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 2.225148e-01 | 0.653 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 2.980908e-01 | 0.526 |
| R-HSA-9960525 | CASP5-mediated substrate cleavage | 2.510373e-01 | 0.600 |
| R-HSA-9706019 | RHOBTB3 ATPase cycle | 2.857681e-01 | 0.544 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 3.431202e-01 | 0.465 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 3.407049e-01 | 0.468 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 3.135015e-01 | 0.504 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 3.954148e-01 | 0.403 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 4.148208e-01 | 0.382 |
| R-HSA-73884 | Base Excision Repair | 2.810632e-01 | 0.551 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 3.028169e-01 | 0.519 |
| R-HSA-9960519 | CASP4-mediated substrate cleavage | 2.510373e-01 | 0.600 |
| R-HSA-9927353 | Co-inhibition by BTLA | 3.907240e-01 | 0.408 |
| R-HSA-390696 | Adrenoceptors | 3.560561e-01 | 0.448 |
| R-HSA-8851680 | Butyrophilin (BTN) family interactions | 4.076628e-01 | 0.390 |
| R-HSA-9659379 | Sensory processing of sound | 4.143079e-01 | 0.383 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 3.038952e-01 | 0.517 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 4.185543e-01 | 0.378 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 4.188685e-01 | 0.378 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 3.547269e-01 | 0.450 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 4.444482e-01 | 0.352 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 4.462545e-01 | 0.350 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 4.462545e-01 | 0.350 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 4.462545e-01 | 0.350 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 4.483164e-01 | 0.348 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 4.502028e-01 | 0.347 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 4.518720e-01 | 0.345 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 4.518720e-01 | 0.345 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 4.518720e-01 | 0.345 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 4.537540e-01 | 0.343 |
| R-HSA-8964038 | LDL clearance | 4.537540e-01 | 0.343 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 4.537540e-01 | 0.343 |
| R-HSA-5358508 | Mismatch Repair | 4.555540e-01 | 0.341 |
| R-HSA-9831926 | Nephron development | 4.555540e-01 | 0.341 |
| R-HSA-2660826 | Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 4.563645e-01 | 0.341 |
| R-HSA-2660825 | Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 4.563645e-01 | 0.341 |
| R-HSA-6791465 | Pentose phosphate pathway disease | 4.563645e-01 | 0.341 |
| R-HSA-5660668 | CLEC7A/inflammasome pathway | 4.563645e-01 | 0.341 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 4.563645e-01 | 0.341 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 4.563645e-01 | 0.341 |
| R-HSA-8985586 | SLIT2:ROBO1 increases RHOA activity | 4.563645e-01 | 0.341 |
| R-HSA-111459 | Activation of caspases through apoptosome-mediated cleavage | 4.563645e-01 | 0.341 |
| R-HSA-5688849 | Defective CSF2RB causes SMDP5 | 4.563645e-01 | 0.341 |
| R-HSA-5688890 | Defective CSF2RA causes SMDP4 | 4.563645e-01 | 0.341 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 4.563645e-01 | 0.341 |
| R-HSA-111469 | SMAC, XIAP-regulated apoptotic response | 4.563645e-01 | 0.341 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 4.563645e-01 | 0.341 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 4.563645e-01 | 0.341 |
| R-HSA-9758919 | Epithelial-Mesenchymal Transition (EMT) during gastrulation | 4.563645e-01 | 0.341 |
| R-HSA-9033500 | TYSND1 cleaves peroxisomal proteins | 4.563645e-01 | 0.341 |
| R-HSA-9860276 | SLC15A4:TASL-dependent IRF5 activation | 4.563645e-01 | 0.341 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 4.563744e-01 | 0.341 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 4.571066e-01 | 0.340 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 4.571066e-01 | 0.340 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 4.571066e-01 | 0.340 |
| R-HSA-435354 | Zinc transporters | 4.571066e-01 | 0.340 |
| R-HSA-8963896 | HDL assembly | 4.571066e-01 | 0.340 |
| R-HSA-9022702 | MECP2 regulates transcription of neuronal ligands | 4.579506e-01 | 0.339 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 4.579506e-01 | 0.339 |
| R-HSA-5140745 | WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 4.579506e-01 | 0.339 |
| R-HSA-5689877 | Josephin domain DUBs | 4.579506e-01 | 0.339 |
| R-HSA-9614085 | FOXO-mediated transcription | 4.606082e-01 | 0.337 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 4.621259e-01 | 0.335 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 4.629990e-01 | 0.334 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 4.656605e-01 | 0.332 |
| R-HSA-6811438 | Intra-Golgi traffic | 4.715251e-01 | 0.326 |
| R-HSA-1296072 | Voltage gated Potassium channels | 4.748033e-01 | 0.323 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 4.748245e-01 | 0.323 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 4.748245e-01 | 0.323 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 4.755385e-01 | 0.323 |
| R-HSA-397795 | G-protein beta:gamma signalling | 4.783854e-01 | 0.320 |
| R-HSA-354192 | Integrin signaling | 4.783854e-01 | 0.320 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 4.784784e-01 | 0.320 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 4.806812e-01 | 0.318 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 4.823556e-01 | 0.317 |
| R-HSA-167287 | HIV elongation arrest and recovery | 4.823556e-01 | 0.317 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 4.823556e-01 | 0.317 |
| R-HSA-912526 | Interleukin receptor SHC signaling | 4.868400e-01 | 0.313 |
| R-HSA-8854691 | Interleukin-20 family signaling | 4.868400e-01 | 0.313 |
| R-HSA-200425 | Carnitine shuttle | 4.868400e-01 | 0.313 |
| R-HSA-982772 | Growth hormone receptor signaling | 4.868400e-01 | 0.313 |
| R-HSA-163685 | Integration of energy metabolism | 4.880082e-01 | 0.312 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 4.920402e-01 | 0.308 |
| R-HSA-110320 | Translesion Synthesis by POLH | 4.920402e-01 | 0.308 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 4.920402e-01 | 0.308 |
| R-HSA-844456 | The NLRP3 inflammasome | 4.920402e-01 | 0.308 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 4.923537e-01 | 0.308 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 4.965668e-01 | 0.304 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 4.965668e-01 | 0.304 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling | 4.983065e-01 | 0.303 |
| R-HSA-9027284 | Erythropoietin activates RAS | 4.983065e-01 | 0.303 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 4.983065e-01 | 0.303 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 4.983065e-01 | 0.303 |
| R-HSA-8876725 | Protein methylation | 4.983065e-01 | 0.303 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 5.013157e-01 | 0.300 |
| R-HSA-73857 | RNA Polymerase II Transcription | 5.013267e-01 | 0.300 |
| R-HSA-4839744 | Signaling by APC mutants | 5.063268e-01 | 0.296 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 5.063268e-01 | 0.296 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 5.063268e-01 | 0.296 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 5.063268e-01 | 0.296 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 5.063268e-01 | 0.296 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 5.063268e-01 | 0.296 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 5.063268e-01 | 0.296 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 5.088375e-01 | 0.293 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 5.123466e-01 | 0.290 |
| R-HSA-177539 | Autointegration results in viral DNA circles | 5.177280e-01 | 0.286 |
| R-HSA-3595172 | Defective CHST3 causes SEDCJD | 5.177280e-01 | 0.286 |
| R-HSA-3595174 | Defective CHST14 causes EDS, musculocontractural type | 5.177280e-01 | 0.286 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 5.177280e-01 | 0.286 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 5.177280e-01 | 0.286 |
| R-HSA-175567 | Integration of viral DNA into host genomic DNA | 5.177280e-01 | 0.286 |
| R-HSA-389542 | NADPH regeneration | 5.177280e-01 | 0.286 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 5.192599e-01 | 0.285 |
| R-HSA-2428924 | IGF1R signaling cascade | 5.233267e-01 | 0.281 |
| R-HSA-192823 | Viral mRNA Translation | 5.270957e-01 | 0.278 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 5.272360e-01 | 0.278 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 5.275876e-01 | 0.278 |
| R-HSA-9033241 | Peroxisomal protein import | 5.281773e-01 | 0.277 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 5.308430e-01 | 0.275 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 5.308430e-01 | 0.275 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 5.308430e-01 | 0.275 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 5.339253e-01 | 0.273 |
| R-HSA-5696400 | Dual Incision in GG-NER | 5.339592e-01 | 0.272 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 5.339592e-01 | 0.272 |
| R-HSA-2206291 | MPS IIIC - Sanfilippo syndrome C | 5.376258e-01 | 0.270 |
| R-HSA-8854521 | Interaction between PHLDA1 and AURKA | 5.376258e-01 | 0.270 |
| R-HSA-5662853 | Essential pentosuria | 5.376258e-01 | 0.270 |
| R-HSA-5619104 | Defective SLC12A1 causes Bartter syndrome 1 (BS1) | 5.376258e-01 | 0.270 |
| R-HSA-5619098 | Defective SLC2A2 causes Fanconi-Bickel syndrome (FBS) | 5.376258e-01 | 0.270 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 5.376258e-01 | 0.270 |
| R-HSA-5357609 | Glycogen storage disease type II (GAA) | 5.376258e-01 | 0.270 |
| R-HSA-68881 | Mitotic Metaphase/Anaphase Transition | 5.376258e-01 | 0.270 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 5.376258e-01 | 0.270 |
| R-HSA-75064 | mRNA Editing: A to I Conversion | 5.376258e-01 | 0.270 |
| R-HSA-446343 | Localization of the PINCH-ILK-PARVIN complex to focal adhesions | 5.376258e-01 | 0.270 |
| R-HSA-194306 | Neurophilin interactions with VEGF and VEGFR | 5.376258e-01 | 0.270 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 5.376258e-01 | 0.270 |
| R-HSA-75102 | C6 deamination of adenosine | 5.376258e-01 | 0.270 |
| R-HSA-75108 | Activation, myristolyation of BID and translocation to mitochondria | 5.376258e-01 | 0.270 |
| R-HSA-9758941 | Gastrulation | 5.380507e-01 | 0.269 |
| R-HSA-9708530 | Regulation of BACH1 activity | 5.380969e-01 | 0.269 |
| R-HSA-176412 | Phosphorylation of the APC/C | 5.380969e-01 | 0.269 |
| R-HSA-73893 | DNA Damage Bypass | 5.392236e-01 | 0.268 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 5.438376e-01 | 0.265 |
| R-HSA-3214858 | RMTs methylate histone arginines | 5.456138e-01 | 0.263 |
| R-HSA-420029 | Tight junction interactions | 5.508446e-01 | 0.259 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 5.508446e-01 | 0.259 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 5.508446e-01 | 0.259 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 5.508446e-01 | 0.259 |
| R-HSA-70221 | Glycogen breakdown (glycogenolysis) | 5.508446e-01 | 0.259 |
| R-HSA-3214842 | HDMs demethylate histones | 5.508446e-01 | 0.259 |
| R-HSA-9623433 | NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis | 5.523538e-01 | 0.258 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 5.523538e-01 | 0.258 |
| R-HSA-2514853 | Condensation of Prometaphase Chromosomes | 5.523538e-01 | 0.258 |
| R-HSA-180689 | APOBEC3G mediated resistance to HIV-1 infection | 5.523538e-01 | 0.258 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 5.523538e-01 | 0.258 |
| R-HSA-5693548 | Sensing of DNA Double Strand Breaks | 5.523538e-01 | 0.258 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 5.523538e-01 | 0.258 |
| R-HSA-4839735 | Signaling by AXIN mutants | 5.523538e-01 | 0.258 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 5.523538e-01 | 0.258 |
| R-HSA-168898 | Toll-like Receptor Cascades | 5.524156e-01 | 0.258 |
| R-HSA-167169 | HIV Transcription Elongation | 5.527690e-01 | 0.257 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 5.527690e-01 | 0.257 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 5.527690e-01 | 0.257 |
| R-HSA-1980143 | Signaling by NOTCH1 | 5.529786e-01 | 0.257 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 5.619896e-01 | 0.250 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 5.619896e-01 | 0.250 |
| R-HSA-69186 | Lagging Strand Synthesis | 5.619896e-01 | 0.250 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 5.694620e-01 | 0.245 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 5.703050e-01 | 0.244 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 5.717623e-01 | 0.243 |
| R-HSA-112315 | Transmission across Chemical Synapses | 5.731608e-01 | 0.242 |
| R-HSA-9022707 | MECP2 regulates transcription factors | 5.742956e-01 | 0.241 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 5.742956e-01 | 0.241 |
| R-HSA-3371599 | Defective HLCS causes multiple carboxylase deficiency | 5.742956e-01 | 0.241 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 5.742956e-01 | 0.241 |
| R-HSA-8948747 | Regulation of PTEN localization | 5.742956e-01 | 0.241 |
| R-HSA-8849473 | PTK6 Expression | 5.742956e-01 | 0.241 |
| R-HSA-163754 | Insulin effects increased synthesis of Xylulose-5-Phosphate | 5.742956e-01 | 0.241 |
| R-HSA-9031525 | NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake | 5.742956e-01 | 0.241 |
| R-HSA-112412 | SOS-mediated signalling | 5.742956e-01 | 0.241 |
| R-HSA-1912399 | Pre-NOTCH Processing in the Endoplasmic Reticulum | 5.742956e-01 | 0.241 |
| R-HSA-72731 | Recycling of eIF2:GDP | 5.742956e-01 | 0.241 |
| R-HSA-3595177 | Defective CHSY1 causes TPBS | 5.742956e-01 | 0.241 |
| R-HSA-9031528 | NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipo... | 5.742956e-01 | 0.241 |
| R-HSA-111367 | SLBP independent Processing of Histone Pre-mRNAs | 5.742956e-01 | 0.241 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 5.742956e-01 | 0.241 |
| R-HSA-9686347 | Microbial modulation of RIPK1-mediated regulated necrosis | 5.742956e-01 | 0.241 |
| R-HSA-5576890 | Phase 3 - rapid repolarisation | 5.742956e-01 | 0.241 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 5.742956e-01 | 0.241 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 5.762232e-01 | 0.239 |
| R-HSA-2892247 | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | 5.762232e-01 | 0.239 |
| R-HSA-5578775 | Ion homeostasis | 5.770442e-01 | 0.239 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 5.770442e-01 | 0.239 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 5.814503e-01 | 0.235 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 5.814503e-01 | 0.235 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 5.820074e-01 | 0.235 |
| R-HSA-1266738 | Developmental Biology | 5.835762e-01 | 0.234 |
| R-HSA-69205 | G1/S-Specific Transcription | 5.871423e-01 | 0.231 |
| R-HSA-9609507 | Protein localization | 5.912802e-01 | 0.228 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 5.927677e-01 | 0.227 |
| R-HSA-9694614 | Attachment and Entry | 5.950785e-01 | 0.225 |
| R-HSA-8851805 | MET activates RAS signaling | 5.957290e-01 | 0.225 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 5.957290e-01 | 0.225 |
| R-HSA-4641265 | Repression of WNT target genes | 5.957290e-01 | 0.225 |
| R-HSA-2691230 | Signaling by NOTCH1 HD Domain Mutants in Cancer | 5.957290e-01 | 0.225 |
| R-HSA-2691232 | Constitutive Signaling by NOTCH1 HD Domain Mutants | 5.957290e-01 | 0.225 |
| R-HSA-8866427 | VLDLR internalisation and degradation | 5.957290e-01 | 0.225 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 5.957290e-01 | 0.225 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 5.957290e-01 | 0.225 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 5.957290e-01 | 0.225 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 5.957290e-01 | 0.225 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 5.957290e-01 | 0.225 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 6.020499e-01 | 0.220 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 6.020499e-01 | 0.220 |
| R-HSA-8951664 | Neddylation | 6.060683e-01 | 0.217 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 6.063859e-01 | 0.217 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 6.063859e-01 | 0.217 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 6.109578e-01 | 0.214 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 6.109578e-01 | 0.214 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 6.124942e-01 | 0.213 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 6.124942e-01 | 0.213 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 6.124942e-01 | 0.213 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 6.124942e-01 | 0.213 |
| R-HSA-6811440 | Retrograde transport at the Trans-Golgi-Network | 6.154716e-01 | 0.211 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 6.177475e-01 | 0.209 |
| R-HSA-9034793 | Activated NTRK3 signals through PLCG1 | 6.187332e-01 | 0.208 |
| R-HSA-167021 | PLC-gamma1 signalling | 6.187332e-01 | 0.208 |
| R-HSA-8866906 | TFAP2 (AP-2) family regulates transcription of other transcription factors | 6.187332e-01 | 0.208 |
| R-HSA-5579000 | Defective CYP1B1 causes Glaucoma | 6.187332e-01 | 0.208 |
| R-HSA-8941237 | Invadopodia formation | 6.187332e-01 | 0.208 |
| R-HSA-5660862 | Defective SLC7A7 causes lysinuric protein intolerance (LPI) | 6.187332e-01 | 0.208 |
| R-HSA-198745 | Signalling to STAT3 | 6.187332e-01 | 0.208 |
| R-HSA-3249367 | STAT6-mediated induction of chemokines | 6.187332e-01 | 0.208 |
| R-HSA-139910 | Activation of BMF and translocation to mitochondria | 6.187332e-01 | 0.208 |
| R-HSA-417973 | Adenosine P1 receptors | 6.187332e-01 | 0.208 |
| R-HSA-111446 | Activation of BIM and translocation to mitochondria | 6.187332e-01 | 0.208 |
| R-HSA-390650 | Histamine receptors | 6.187332e-01 | 0.208 |
| R-HSA-9854907 | Regulation of MITF-M dependent genes involved in metabolism | 6.187332e-01 | 0.208 |
| R-HSA-75157 | FasL/ CD95L signaling | 6.187332e-01 | 0.208 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 6.213942e-01 | 0.207 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 6.213942e-01 | 0.207 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 6.221624e-01 | 0.206 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 6.248289e-01 | 0.204 |
| R-HSA-3371378 | Regulation by c-FLIP | 6.258616e-01 | 0.204 |
| R-HSA-164940 | Nef mediated downregulation of MHC class I complex cell surface expression | 6.258616e-01 | 0.204 |
| R-HSA-212718 | EGFR interacts with phospholipase C-gamma | 6.258616e-01 | 0.204 |
| R-HSA-69416 | Dimerization of procaspase-8 | 6.258616e-01 | 0.204 |
| R-HSA-190370 | FGFR1b ligand binding and activation | 6.258616e-01 | 0.204 |
| R-HSA-193634 | Axonal growth inhibition (RHOA activation) | 6.258616e-01 | 0.204 |
| R-HSA-9020933 | Interleukin-23 signaling | 6.258616e-01 | 0.204 |
| R-HSA-77588 | SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs | 6.258616e-01 | 0.204 |
| R-HSA-111453 | BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members | 6.258616e-01 | 0.204 |
| R-HSA-9927354 | Co-stimulation by ICOS | 6.258616e-01 | 0.204 |
| R-HSA-6803529 | FGFR2 alternative splicing | 6.267231e-01 | 0.203 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 6.267231e-01 | 0.203 |
| R-HSA-936837 | Ion transport by P-type ATPases | 6.303665e-01 | 0.200 |
| R-HSA-114608 | Platelet degranulation | 6.305301e-01 | 0.200 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 6.333412e-01 | 0.198 |
| R-HSA-72766 | Translation | 6.334253e-01 | 0.198 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 6.362649e-01 | 0.196 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 6.371728e-01 | 0.196 |
| R-HSA-8875878 | MET promotes cell motility | 6.372331e-01 | 0.196 |
| R-HSA-70263 | Gluconeogenesis | 6.375220e-01 | 0.196 |
| R-HSA-186712 | Regulation of beta-cell development | 6.389775e-01 | 0.195 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 6.392718e-01 | 0.194 |
| R-HSA-77387 | Insulin receptor recycling | 6.392718e-01 | 0.194 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 6.421038e-01 | 0.192 |
| R-HSA-9610379 | HCMV Late Events | 6.421038e-01 | 0.192 |
| R-HSA-977225 | Amyloid fiber formation | 6.435361e-01 | 0.191 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 6.467763e-01 | 0.189 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 6.467763e-01 | 0.189 |
| R-HSA-111471 | Apoptotic factor-mediated response | 6.467763e-01 | 0.189 |
| R-HSA-112316 | Neuronal System | 6.489291e-01 | 0.188 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 6.505910e-01 | 0.187 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 6.505910e-01 | 0.187 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 6.505910e-01 | 0.187 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 6.531320e-01 | 0.185 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 6.568262e-01 | 0.183 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 6.585323e-01 | 0.181 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 6.585323e-01 | 0.181 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 6.585323e-01 | 0.181 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 6.585323e-01 | 0.181 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 6.585323e-01 | 0.181 |
| R-HSA-351202 | Metabolism of polyamines | 6.585323e-01 | 0.181 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 6.592016e-01 | 0.181 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 6.609549e-01 | 0.180 |
| R-HSA-72312 | rRNA processing | 6.656930e-01 | 0.177 |
| R-HSA-9012852 | Signaling by NOTCH3 | 6.684963e-01 | 0.175 |
| R-HSA-70268 | Pyruvate metabolism | 6.693806e-01 | 0.174 |
| R-HSA-2172127 | DAP12 interactions | 6.705462e-01 | 0.174 |
| R-HSA-170984 | ARMS-mediated activation | 6.724402e-01 | 0.172 |
| R-HSA-193692 | Regulated proteolysis of p75NTR | 6.724402e-01 | 0.172 |
| R-HSA-5218900 | CASP8 activity is inhibited | 6.724402e-01 | 0.172 |
| R-HSA-193697 | p75NTR regulates axonogenesis | 6.724402e-01 | 0.172 |
| R-HSA-8866907 | Activation of the TFAP2 (AP-2) family of transcription factors | 6.724402e-01 | 0.172 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 6.724402e-01 | 0.172 |
| R-HSA-3323169 | Defects in biotin (Btn) metabolism | 6.724402e-01 | 0.172 |
| R-HSA-5649702 | APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement P... | 6.724402e-01 | 0.172 |
| R-HSA-9762293 | Regulation of CDH11 gene transcription | 6.724402e-01 | 0.172 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 6.724402e-01 | 0.172 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 6.738688e-01 | 0.171 |
| R-HSA-69166 | Removal of the Flap Intermediate | 6.738688e-01 | 0.171 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 6.738688e-01 | 0.171 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 6.738688e-01 | 0.171 |
| R-HSA-5578768 | Physiological factors | 6.738688e-01 | 0.171 |
| R-HSA-5673000 | RAF activation | 6.752728e-01 | 0.171 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 6.770207e-01 | 0.169 |
| R-HSA-429958 | mRNA decay by 3' to 5' exoribonuclease | 6.789864e-01 | 0.168 |
| R-HSA-9694631 | Maturation of nucleoprotein | 6.789864e-01 | 0.168 |
| R-HSA-1989781 | PPARA activates gene expression | 6.829223e-01 | 0.166 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 6.837312e-01 | 0.165 |
| R-HSA-5260271 | Diseases of Immune System | 6.837312e-01 | 0.165 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 6.837312e-01 | 0.165 |
| R-HSA-8982491 | Glycogen metabolism | 6.837312e-01 | 0.165 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 6.853219e-01 | 0.164 |
| R-HSA-1296061 | HCN channels | 6.856169e-01 | 0.164 |
| R-HSA-9026527 | Activated NTRK2 signals through PLCG1 | 6.856169e-01 | 0.164 |
| R-HSA-9735763 | Defective PNP disrupts phosphorolysis of (deoxy)guanosine and (deoxy)inosine | 6.856169e-01 | 0.164 |
| R-HSA-9735786 | Nucleotide catabolism defects | 6.856169e-01 | 0.164 |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity | 6.856169e-01 | 0.164 |
| R-HSA-8952158 | RUNX3 regulates BCL2L11 (BIM) transcription | 6.856169e-01 | 0.164 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 6.856169e-01 | 0.164 |
| R-HSA-9692913 | SARS-CoV-1-mediated effects on programmed cell death | 6.856169e-01 | 0.164 |
| R-HSA-388479 | Vasopressin-like receptors | 6.856169e-01 | 0.164 |
| R-HSA-111448 | Activation of NOXA and translocation to mitochondria | 6.856169e-01 | 0.164 |
| R-HSA-5626978 | TNFR1-mediated ceramide production | 6.856169e-01 | 0.164 |
| R-HSA-193670 | p75NTR negatively regulates cell cycle via SC1 | 6.856169e-01 | 0.164 |
| R-HSA-9729555 | Sensory perception of sour taste | 6.856169e-01 | 0.164 |
| R-HSA-9707587 | Regulation of HMOX1 expression and activity | 6.856169e-01 | 0.164 |
| R-HSA-9007892 | Interleukin-38 signaling | 6.856169e-01 | 0.164 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 6.917422e-01 | 0.160 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 6.920484e-01 | 0.160 |
| R-HSA-114452 | Activation of BH3-only proteins | 6.920484e-01 | 0.160 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 6.941940e-01 | 0.159 |
| R-HSA-422356 | Regulation of insulin secretion | 7.003907e-01 | 0.155 |
| R-HSA-212436 | Generic Transcription Pathway | 7.007558e-01 | 0.154 |
| R-HSA-9694548 | Maturation of spike protein | 7.055285e-01 | 0.151 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 7.085247e-01 | 0.150 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 7.085247e-01 | 0.150 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 7.085247e-01 | 0.150 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 7.085247e-01 | 0.150 |
| R-HSA-196780 | Biotin transport and metabolism | 7.085247e-01 | 0.150 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 7.085247e-01 | 0.150 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 7.085247e-01 | 0.150 |
| R-HSA-3322077 | Glycogen synthesis | 7.090852e-01 | 0.149 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 7.090852e-01 | 0.149 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 7.120677e-01 | 0.147 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 7.121717e-01 | 0.147 |
| R-HSA-1660516 | Synthesis of PIPs at the early endosome membrane | 7.121717e-01 | 0.147 |
| R-HSA-173107 | Binding and entry of HIV virion | 7.141941e-01 | 0.146 |
| R-HSA-9664873 | Pexophagy | 7.141941e-01 | 0.146 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 7.141941e-01 | 0.146 |
| R-HSA-9762292 | Regulation of CDH11 function | 7.141941e-01 | 0.146 |
| R-HSA-198203 | PI3K/AKT activation | 7.141941e-01 | 0.146 |
| R-HSA-9693928 | Defective RIPK1-mediated regulated necrosis | 7.141941e-01 | 0.146 |
| R-HSA-9761174 | Formation of intermediate mesoderm | 7.141941e-01 | 0.146 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 7.141941e-01 | 0.146 |
| R-HSA-9683686 | Maturation of spike protein | 7.141941e-01 | 0.146 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 7.141941e-01 | 0.146 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 7.153695e-01 | 0.145 |
| R-HSA-162588 | Budding and maturation of HIV virion | 7.164260e-01 | 0.145 |
| R-HSA-5694530 | Cargo concentration in the ER | 7.164260e-01 | 0.145 |
| R-HSA-8941326 | RUNX2 regulates bone development | 7.212440e-01 | 0.142 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 7.212440e-01 | 0.142 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 7.212440e-01 | 0.142 |
| R-HSA-74158 | RNA Polymerase III Transcription | 7.212440e-01 | 0.142 |
| R-HSA-163560 | Triglyceride catabolism | 7.212440e-01 | 0.142 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 7.243077e-01 | 0.140 |
| R-HSA-6782135 | Dual incision in TC-NER | 7.245775e-01 | 0.140 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 7.269467e-01 | 0.138 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 7.269467e-01 | 0.138 |
| R-HSA-877300 | Interferon gamma signaling | 7.282253e-01 | 0.138 |
| R-HSA-109582 | Hemostasis | 7.351449e-01 | 0.134 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 7.366909e-01 | 0.133 |
| R-HSA-445355 | Smooth Muscle Contraction | 7.366909e-01 | 0.133 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 7.370704e-01 | 0.132 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 7.370704e-01 | 0.132 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 7.373620e-01 | 0.132 |
| R-HSA-5689901 | Metalloprotease DUBs | 7.373620e-01 | 0.132 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 7.373620e-01 | 0.132 |
| R-HSA-9937080 | Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 7.394363e-01 | 0.131 |
| R-HSA-4791275 | Signaling by WNT in cancer | 7.394363e-01 | 0.131 |
| R-HSA-2024096 | HS-GAG degradation | 7.394363e-01 | 0.131 |
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand | 7.402768e-01 | 0.131 |
| R-HSA-399955 | SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 7.402768e-01 | 0.131 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 7.402768e-01 | 0.131 |
| R-HSA-169893 | Prolonged ERK activation events | 7.402768e-01 | 0.131 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 7.402768e-01 | 0.131 |
| R-HSA-434316 | Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion | 7.402768e-01 | 0.131 |
| R-HSA-9818026 | NFE2L2 regulating inflammation associated genes | 7.407706e-01 | 0.130 |
| R-HSA-9032759 | NTRK2 activates RAC1 | 7.407706e-01 | 0.130 |
| R-HSA-9673221 | Defective F9 activation | 7.407706e-01 | 0.130 |
| R-HSA-9846298 | Defective binding of VWF variant to GPIb:IX:V | 7.407706e-01 | 0.130 |
| R-HSA-9845620 | Enhanced binding of GP1BA variant to VWF multimer:collagen | 7.407706e-01 | 0.130 |
| R-HSA-9931529 | Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK | 7.407706e-01 | 0.130 |
| R-HSA-8849474 | PTK6 Activates STAT3 | 7.407706e-01 | 0.130 |
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN | 7.407706e-01 | 0.130 |
| R-HSA-8849472 | PTK6 Down-Regulation | 7.407706e-01 | 0.130 |
| R-HSA-420597 | Nectin/Necl trans heterodimerization | 7.407706e-01 | 0.130 |
| R-HSA-5624138 | Trafficking of myristoylated proteins to the cilium | 7.407706e-01 | 0.130 |
| R-HSA-8849468 | PTK6 Regulates Proteins Involved in RNA Processing | 7.407706e-01 | 0.130 |
| R-HSA-390648 | Muscarinic acetylcholine receptors | 7.407706e-01 | 0.130 |
| R-HSA-71737 | Pyrophosphate hydrolysis | 7.407706e-01 | 0.130 |
| R-HSA-435368 | Zinc efflux and compartmentalization by the SLC30 family | 7.407706e-01 | 0.130 |
| R-HSA-168316 | Assembly of Viral Components at the Budding Site | 7.407706e-01 | 0.130 |
| R-HSA-9031628 | NGF-stimulated transcription | 7.500393e-01 | 0.125 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 7.513825e-01 | 0.124 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS | 7.513825e-01 | 0.124 |
| R-HSA-9832991 | Formation of the posterior neural plate | 7.513825e-01 | 0.124 |
| R-HSA-9754560 | SARS-CoV-2 modulates autophagy | 7.513825e-01 | 0.124 |
| R-HSA-425381 | Bicarbonate transporters | 7.513825e-01 | 0.124 |
| R-HSA-391908 | Prostanoid ligand receptors | 7.513825e-01 | 0.124 |
| R-HSA-1483248 | Synthesis of PIPs at the ER membrane | 7.513825e-01 | 0.124 |
| R-HSA-5682910 | LGI-ADAM interactions | 7.513825e-01 | 0.124 |
| R-HSA-75205 | Dissolution of Fibrin Clot | 7.513825e-01 | 0.124 |
| R-HSA-379724 | tRNA Aminoacylation | 7.583487e-01 | 0.120 |
| R-HSA-201451 | Signaling by BMP | 7.608997e-01 | 0.119 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 7.610786e-01 | 0.119 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 7.625704e-01 | 0.118 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 7.629701e-01 | 0.117 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 7.629701e-01 | 0.117 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 7.692150e-01 | 0.114 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 7.692150e-01 | 0.114 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 7.741249e-01 | 0.111 |
| R-HSA-445717 | Aquaporin-mediated transport | 7.741249e-01 | 0.111 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 7.813655e-01 | 0.107 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 7.813655e-01 | 0.107 |
| R-HSA-71336 | Pentose phosphate pathway | 7.814886e-01 | 0.107 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 7.814886e-01 | 0.107 |
| R-HSA-5683826 | Surfactant metabolism | 7.826125e-01 | 0.106 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 7.828099e-01 | 0.106 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 7.828099e-01 | 0.106 |
| R-HSA-451326 | Activation of kainate receptors upon glutamate binding | 7.828099e-01 | 0.106 |
| R-HSA-622312 | Inflammasomes | 7.828099e-01 | 0.106 |
| R-HSA-9837999 | Mitochondrial protein degradation | 7.831941e-01 | 0.106 |
| R-HSA-1234158 | Regulation of gene expression by Hypoxia-inducible Factor | 7.843220e-01 | 0.106 |
| R-HSA-2022923 | DS-GAG biosynthesis | 7.843220e-01 | 0.106 |
| R-HSA-9026519 | Activated NTRK2 signals through RAS | 7.843220e-01 | 0.106 |
| R-HSA-1250342 | PI3K events in ERBB4 signaling | 7.843220e-01 | 0.106 |
| R-HSA-1236977 | Endosomal/Vacuolar pathway | 7.843220e-01 | 0.106 |
| R-HSA-113501 | Inhibition of replication initiation of damaged DNA by RB1/E2F1 | 7.843220e-01 | 0.106 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 7.843220e-01 | 0.106 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 7.843220e-01 | 0.106 |
| R-HSA-109704 | PI3K Cascade | 7.843972e-01 | 0.105 |
| R-HSA-164525 | Plus-strand DNA synthesis | 7.862510e-01 | 0.104 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 7.862510e-01 | 0.104 |
| R-HSA-5638302 | Signaling by Overexpressed Wild-Type EGFR in Cancer | 7.862510e-01 | 0.104 |
| R-HSA-111957 | Cam-PDE 1 activation | 7.862510e-01 | 0.104 |
| R-HSA-9017802 | Noncanonical activation of NOTCH3 | 7.862510e-01 | 0.104 |
| R-HSA-5638303 | Inhibition of Signaling by Overexpressed EGFR | 7.862510e-01 | 0.104 |
| R-HSA-5340588 | Signaling by RNF43 mutants | 7.862510e-01 | 0.104 |
| R-HSA-9652817 | Signaling by MAPK mutants | 7.862510e-01 | 0.104 |
| R-HSA-389397 | Orexin and neuropeptides FF and QRFP bind to their respective receptors | 7.862510e-01 | 0.104 |
| R-HSA-187024 | NGF-independant TRKA activation | 7.862510e-01 | 0.104 |
| R-HSA-165160 | PDE3B signalling | 7.862510e-01 | 0.104 |
| R-HSA-1483101 | Synthesis of PS | 7.862510e-01 | 0.104 |
| R-HSA-109703 | PKB-mediated events | 7.862510e-01 | 0.104 |
| R-HSA-193681 | Ceramide signalling | 7.862510e-01 | 0.104 |
| R-HSA-9823587 | Defects of platelet adhesion to exposed collagen | 7.862510e-01 | 0.104 |
| R-HSA-8981373 | Intestinal hexose absorption | 7.862510e-01 | 0.104 |
| R-HSA-195399 | VEGF binds to VEGFR leading to receptor dimerization | 7.862510e-01 | 0.104 |
| R-HSA-187706 | Signalling to p38 via RIT and RIN | 7.862510e-01 | 0.104 |
| R-HSA-444821 | Relaxin receptors | 7.862510e-01 | 0.104 |
| R-HSA-194313 | VEGF ligand-receptor interactions | 7.862510e-01 | 0.104 |
| R-HSA-5632681 | Ligand-receptor interactions | 7.862510e-01 | 0.104 |
| R-HSA-111457 | Release of apoptotic factors from the mitochondria | 7.862510e-01 | 0.104 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 7.862510e-01 | 0.104 |
| R-HSA-75158 | TRAIL signaling | 7.862510e-01 | 0.104 |
| R-HSA-9669938 | Signaling by KIT in disease | 7.868372e-01 | 0.104 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 7.868372e-01 | 0.104 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 7.868372e-01 | 0.104 |
| R-HSA-166208 | mTORC1-mediated signalling | 7.868372e-01 | 0.104 |
| R-HSA-9857377 | Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autopha... | 7.868372e-01 | 0.104 |
| R-HSA-1268020 | Mitochondrial protein import | 7.891614e-01 | 0.103 |
| R-HSA-186797 | Signaling by PDGF | 7.891614e-01 | 0.103 |
| R-HSA-9833110 | RSV-host interactions | 7.909790e-01 | 0.102 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 7.954630e-01 | 0.099 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 7.954630e-01 | 0.099 |
| R-HSA-3229121 | Glycogen storage diseases | 7.954630e-01 | 0.099 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 7.954630e-01 | 0.099 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 7.992610e-01 | 0.097 |
| R-HSA-202433 | Generation of second messenger molecules | 7.992610e-01 | 0.097 |
| R-HSA-1980145 | Signaling by NOTCH2 | 8.003206e-01 | 0.097 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 8.003206e-01 | 0.097 |
| R-HSA-1971475 | Glycosaminoglycan-protein linkage region biosynthesis | 8.003206e-01 | 0.097 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 8.031322e-01 | 0.095 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 8.031322e-01 | 0.095 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 8.031322e-01 | 0.095 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 8.087438e-01 | 0.092 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 8.087438e-01 | 0.092 |
| R-HSA-9830674 | Formation of the ureteric bud | 8.087438e-01 | 0.092 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 8.099507e-01 | 0.092 |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation | 8.133587e-01 | 0.090 |
| R-HSA-5687613 | Diseases associated with surfactant metabolism | 8.133587e-01 | 0.090 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 8.133587e-01 | 0.090 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 8.133587e-01 | 0.090 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 8.158804e-01 | 0.088 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 8.158804e-01 | 0.088 |
| R-HSA-73817 | Purine ribonucleoside monophosphate biosynthesis | 8.159105e-01 | 0.088 |
| R-HSA-74751 | Insulin receptor signalling cascade | 8.170383e-01 | 0.088 |
| R-HSA-917977 | Transferrin endocytosis and recycling | 8.179773e-01 | 0.087 |
| R-HSA-9843745 | Adipogenesis | 8.185871e-01 | 0.087 |
| R-HSA-180292 | GAB1 signalosome | 8.191675e-01 | 0.087 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 8.191675e-01 | 0.087 |
| R-HSA-428643 | Organic anion transport by SLC5/17/25 transporters | 8.191675e-01 | 0.087 |
| R-HSA-210993 | Tie2 Signaling | 8.191675e-01 | 0.087 |
| R-HSA-9679504 | Translation of Replicase and Assembly of the Replication Transcription Complex | 8.191675e-01 | 0.087 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 8.219182e-01 | 0.085 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 8.219182e-01 | 0.085 |
| R-HSA-9842640 | Signaling by LTK in cancer | 8.237543e-01 | 0.084 |
| R-HSA-8964026 | Chylomicron clearance | 8.237543e-01 | 0.084 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 8.237543e-01 | 0.084 |
| R-HSA-5263617 | Metabolism of ingested MeSeO2H into MeSeH | 8.237543e-01 | 0.084 |
| R-HSA-162585 | Uncoating of the HIV Virion | 8.237543e-01 | 0.084 |
| R-HSA-113507 | E2F-enabled inhibition of pre-replication complex formation | 8.237543e-01 | 0.084 |
| R-HSA-5619070 | Defective SLC16A1 causes symptomatic deficiency in lactate transport (SDLT) | 8.237543e-01 | 0.084 |
| R-HSA-1483152 | Hydrolysis of LPE | 8.237543e-01 | 0.084 |
| R-HSA-6806942 | MET Receptor Activation | 8.237543e-01 | 0.084 |
| R-HSA-8939256 | RUNX1 regulates transcription of genes involved in WNT signaling | 8.237543e-01 | 0.084 |
| R-HSA-447043 | Neurofascin interactions | 8.237543e-01 | 0.084 |
| R-HSA-8951671 | RUNX3 regulates YAP1-mediated transcription | 8.237543e-01 | 0.084 |
| R-HSA-391906 | Leukotriene receptors | 8.237543e-01 | 0.084 |
| R-HSA-74752 | Signaling by Insulin receptor | 8.264373e-01 | 0.083 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 8.287764e-01 | 0.082 |
| R-HSA-9865881 | Complex III assembly | 8.287764e-01 | 0.082 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 8.287764e-01 | 0.082 |
| R-HSA-180786 | Extension of Telomeres | 8.293252e-01 | 0.081 |
| R-HSA-190373 | FGFR1c ligand binding and activation | 8.388478e-01 | 0.076 |
| R-HSA-170968 | Frs2-mediated activation | 8.388478e-01 | 0.076 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 8.388478e-01 | 0.076 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 8.388478e-01 | 0.076 |
| R-HSA-9683610 | Maturation of nucleoprotein | 8.388478e-01 | 0.076 |
| R-HSA-1475029 | Reversible hydration of carbon dioxide | 8.388478e-01 | 0.076 |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome | 8.388478e-01 | 0.076 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 8.392287e-01 | 0.076 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 8.404902e-01 | 0.075 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 8.404902e-01 | 0.075 |
| R-HSA-113510 | E2F mediated regulation of DNA replication | 8.404902e-01 | 0.075 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 8.404902e-01 | 0.075 |
| R-HSA-5619084 | ABC transporter disorders | 8.433380e-01 | 0.074 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 8.448585e-01 | 0.073 |
| R-HSA-3000157 | Laminin interactions | 8.470320e-01 | 0.072 |
| R-HSA-1482801 | Acyl chain remodelling of PS | 8.470320e-01 | 0.072 |
| R-HSA-9830364 | Formation of the nephric duct | 8.470320e-01 | 0.072 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 8.495659e-01 | 0.071 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 8.496908e-01 | 0.071 |
| R-HSA-983712 | Ion channel transport | 8.540504e-01 | 0.069 |
| R-HSA-8931987 | RUNX1 regulates estrogen receptor mediated transcription | 8.546791e-01 | 0.068 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 8.546791e-01 | 0.068 |
| R-HSA-190371 | FGFR3b ligand binding and activation | 8.546791e-01 | 0.068 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 8.546791e-01 | 0.068 |
| R-HSA-203641 | NOSTRIN mediated eNOS trafficking | 8.546791e-01 | 0.068 |
| R-HSA-1614603 | Cysteine formation from homocysteine | 8.546791e-01 | 0.068 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 8.546791e-01 | 0.068 |
| R-HSA-8964046 | VLDL clearance | 8.546791e-01 | 0.068 |
| R-HSA-187015 | Activation of TRKA receptors | 8.546791e-01 | 0.068 |
| R-HSA-418886 | Netrin mediated repulsion signals | 8.546791e-01 | 0.068 |
| R-HSA-167590 | Nef Mediated CD4 Down-regulation | 8.546791e-01 | 0.068 |
| R-HSA-2892245 | POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation | 8.546791e-01 | 0.068 |
| R-HSA-110357 | Displacement of DNA glycosylase by APEX1 | 8.546791e-01 | 0.068 |
| R-HSA-418597 | G alpha (z) signalling events | 8.549225e-01 | 0.068 |
| R-HSA-5654743 | Signaling by FGFR4 | 8.594403e-01 | 0.066 |
| R-HSA-1181150 | Signaling by NODAL | 8.596008e-01 | 0.066 |
| R-HSA-445144 | Signal transduction by L1 | 8.596008e-01 | 0.066 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 8.596008e-01 | 0.066 |
| R-HSA-5654227 | Phospholipase C-mediated cascade; FGFR3 | 8.611403e-01 | 0.065 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 8.611403e-01 | 0.065 |
| R-HSA-1483115 | Hydrolysis of LPC | 8.611403e-01 | 0.065 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 8.611403e-01 | 0.065 |
| R-HSA-1170546 | Prolactin receptor signaling | 8.611403e-01 | 0.065 |
| R-HSA-9686114 | Non-canonical inflammasome activation | 8.611403e-01 | 0.065 |
| R-HSA-9679514 | SARS-CoV-1 Genome Replication and Transcription | 8.611403e-01 | 0.065 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 8.635969e-01 | 0.064 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 8.635969e-01 | 0.064 |
| R-HSA-2122948 | Activated NOTCH1 Transmits Signal to the Nucleus | 8.636144e-01 | 0.064 |
| R-HSA-1236394 | Signaling by ERBB4 | 8.640166e-01 | 0.063 |
| R-HSA-1226099 | Signaling by FGFR in disease | 8.640166e-01 | 0.063 |
| R-HSA-9658195 | Leishmania infection | 8.725750e-01 | 0.059 |
| R-HSA-9824443 | Parasitic Infection Pathways | 8.725750e-01 | 0.059 |
| R-HSA-168256 | Immune System | 8.731702e-01 | 0.059 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 8.744249e-01 | 0.058 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 8.745118e-01 | 0.058 |
| R-HSA-2979096 | NOTCH2 Activation and Transmission of Signal to the Nucleus | 8.766713e-01 | 0.057 |
| R-HSA-202040 | G-protein activation | 8.766713e-01 | 0.057 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 8.766713e-01 | 0.057 |
| R-HSA-196836 | Vitamin C (ascorbate) metabolism | 8.766713e-01 | 0.057 |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane | 8.766713e-01 | 0.057 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 8.766713e-01 | 0.057 |
| R-HSA-112399 | IRS-mediated signalling | 8.774102e-01 | 0.057 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 8.786313e-01 | 0.056 |
| R-HSA-162589 | Reverse Transcription of HIV RNA | 8.801792e-01 | 0.055 |
| R-HSA-164516 | Minus-strand DNA synthesis | 8.801792e-01 | 0.055 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 8.801792e-01 | 0.055 |
| R-HSA-111995 | phospho-PLA2 pathway | 8.801792e-01 | 0.055 |
| R-HSA-1169092 | Activation of RAS in B cells | 8.801792e-01 | 0.055 |
| R-HSA-8866904 | Negative regulation of activity of TFAP2 (AP-2) family transcription factors | 8.801792e-01 | 0.055 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 8.801792e-01 | 0.055 |
| R-HSA-210455 | Astrocytic Glutamate-Glutamine Uptake And Metabolism | 8.801792e-01 | 0.055 |
| R-HSA-112313 | Neurotransmitter uptake and metabolism In glial cells | 8.801792e-01 | 0.055 |
| R-HSA-9839383 | TGFBR3 PTM regulation | 8.801792e-01 | 0.055 |
| R-HSA-1462054 | Alpha-defensins | 8.801792e-01 | 0.055 |
| R-HSA-8963676 | Intestinal absorption | 8.801792e-01 | 0.055 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 8.805730e-01 | 0.055 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 8.805730e-01 | 0.055 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 8.805730e-01 | 0.055 |
| R-HSA-5654228 | Phospholipase C-mediated cascade; FGFR4 | 8.805730e-01 | 0.055 |
| R-HSA-110312 | Translesion synthesis by REV1 | 8.805730e-01 | 0.055 |
| R-HSA-9857492 | Protein lipoylation | 8.805730e-01 | 0.055 |
| R-HSA-416700 | Other semaphorin interactions | 8.805730e-01 | 0.055 |
| R-HSA-9823739 | Formation of the anterior neural plate | 8.805730e-01 | 0.055 |
| R-HSA-419408 | Lysosphingolipid and LPA receptors | 8.805730e-01 | 0.055 |
| R-HSA-5654741 | Signaling by FGFR3 | 8.835051e-01 | 0.054 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 8.910262e-01 | 0.050 |
| R-HSA-9694635 | Translation of Structural Proteins | 8.918136e-01 | 0.050 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 8.918726e-01 | 0.050 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 8.918726e-01 | 0.050 |
| R-HSA-175474 | Assembly Of The HIV Virion | 8.918726e-01 | 0.050 |
| R-HSA-9755088 | Ribavirin ADME | 8.918726e-01 | 0.050 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 8.921918e-01 | 0.050 |
| R-HSA-171319 | Telomere Extension By Telomerase | 8.921918e-01 | 0.050 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 8.921918e-01 | 0.050 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 8.951366e-01 | 0.048 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 8.954976e-01 | 0.048 |
| R-HSA-9664417 | Leishmania phagocytosis | 8.954976e-01 | 0.048 |
| R-HSA-9664407 | Parasite infection | 8.954976e-01 | 0.048 |
| R-HSA-9706369 | Negative regulation of FLT3 | 8.974630e-01 | 0.047 |
| R-HSA-5656121 | Translesion synthesis by POLI | 8.974630e-01 | 0.047 |
| R-HSA-5635838 | Activation of SMO | 8.974630e-01 | 0.047 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 8.974630e-01 | 0.047 |
| R-HSA-8956320 | Nucleotide biosynthesis | 9.000107e-01 | 0.046 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 9.012059e-01 | 0.045 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 9.012059e-01 | 0.045 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 9.012059e-01 | 0.045 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 9.012059e-01 | 0.045 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 9.012059e-01 | 0.045 |
| R-HSA-75072 | mRNA Editing | 9.012059e-01 | 0.045 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 9.012059e-01 | 0.045 |
| R-HSA-9768777 | Regulation of NPAS4 gene transcription | 9.012059e-01 | 0.045 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 9.014994e-01 | 0.045 |
| R-HSA-72086 | mRNA Capping | 9.044041e-01 | 0.044 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 9.044041e-01 | 0.044 |
| R-HSA-418360 | Platelet calcium homeostasis | 9.044041e-01 | 0.044 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 9.044041e-01 | 0.044 |
| R-HSA-909733 | Interferon alpha/beta signaling | 9.048109e-01 | 0.043 |
| R-HSA-2408522 | Selenoamino acid metabolism | 9.050545e-01 | 0.043 |
| R-HSA-9694676 | Translation of Replicase and Assembly of the Replication Transcription Complex | 9.053706e-01 | 0.043 |
| R-HSA-8873719 | RAB geranylgeranylation | 9.057207e-01 | 0.043 |
| R-HSA-5576891 | Cardiac conduction | 9.060115e-01 | 0.043 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 9.061606e-01 | 0.043 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 9.061606e-01 | 0.043 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 9.092774e-01 | 0.041 |
| R-HSA-9830369 | Kidney development | 9.112257e-01 | 0.040 |
| R-HSA-5576893 | Phase 2 - plateau phase | 9.121041e-01 | 0.040 |
| R-HSA-5655862 | Translesion synthesis by POLK | 9.121041e-01 | 0.040 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 9.121041e-01 | 0.040 |
| R-HSA-70370 | Galactose catabolism | 9.121041e-01 | 0.040 |
| R-HSA-1483148 | Synthesis of PG | 9.121041e-01 | 0.040 |
| R-HSA-5660526 | Response to metal ions | 9.121041e-01 | 0.040 |
| R-HSA-5654738 | Signaling by FGFR2 | 9.147834e-01 | 0.039 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 9.173243e-01 | 0.037 |
| R-HSA-400451 | Free fatty acids regulate insulin secretion | 9.173243e-01 | 0.037 |
| R-HSA-1236973 | Cross-presentation of particulate exogenous antigens (phagosomes) | 9.185437e-01 | 0.037 |
| R-HSA-5221030 | TET1,2,3 and TDG demethylate DNA | 9.185437e-01 | 0.037 |
| R-HSA-68952 | DNA replication initiation | 9.185437e-01 | 0.037 |
| R-HSA-9668250 | Defective factor IX causes hemophilia B | 9.185437e-01 | 0.037 |
| R-HSA-111458 | Formation of apoptosome | 9.185437e-01 | 0.037 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 9.185437e-01 | 0.037 |
| R-HSA-2672351 | Stimuli-sensing channels | 9.227713e-01 | 0.035 |
| R-HSA-917937 | Iron uptake and transport | 9.232729e-01 | 0.035 |
| R-HSA-5654736 | Signaling by FGFR1 | 9.247535e-01 | 0.034 |
| R-HSA-5654219 | Phospholipase C-mediated cascade: FGFR1 | 9.247655e-01 | 0.034 |
| R-HSA-139853 | Elevation of cytosolic Ca2+ levels | 9.247655e-01 | 0.034 |
| R-HSA-1660517 | Synthesis of PIPs at the late endosome membrane | 9.247655e-01 | 0.034 |
| R-HSA-4641263 | Regulation of FZD by ubiquitination | 9.247655e-01 | 0.034 |
| R-HSA-1614517 | Sulfide oxidation to sulfate | 9.247655e-01 | 0.034 |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome | 9.247655e-01 | 0.034 |
| R-HSA-8948216 | Collagen chain trimerization | 9.252044e-01 | 0.034 |
| R-HSA-2129379 | Molecules associated with elastic fibres | 9.252058e-01 | 0.034 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 9.278842e-01 | 0.033 |
| R-HSA-204005 | COPII-mediated vesicle transport | 9.319008e-01 | 0.031 |
| R-HSA-190377 | FGFR2b ligand binding and activation | 9.328396e-01 | 0.030 |
| R-HSA-192905 | vRNP Assembly | 9.328396e-01 | 0.030 |
| R-HSA-210747 | Regulation of gene expression in early pancreatic precursor cells | 9.328396e-01 | 0.030 |
| R-HSA-1483226 | Synthesis of PI | 9.328396e-01 | 0.030 |
| R-HSA-77108 | Utilization of Ketone Bodies | 9.328396e-01 | 0.030 |
| R-HSA-9758890 | Transport of RCbl within the body | 9.328396e-01 | 0.030 |
| R-HSA-427601 | Inorganic anion exchange by SLC26 transporters | 9.328396e-01 | 0.030 |
| R-HSA-8963888 | Chylomicron assembly | 9.328396e-01 | 0.030 |
| R-HSA-9635465 | Suppression of apoptosis | 9.328396e-01 | 0.030 |
| R-HSA-190242 | FGFR1 ligand binding and activation | 9.356908e-01 | 0.029 |
| R-HSA-73980 | RNA Polymerase III Transcription Termination | 9.356908e-01 | 0.029 |
| R-HSA-2564830 | Cytosolic iron-sulfur cluster assembly | 9.356908e-01 | 0.029 |
| R-HSA-418038 | Nucleotide-like (purinergic) receptors | 9.356908e-01 | 0.029 |
| R-HSA-1474290 | Collagen formation | 9.359135e-01 | 0.029 |
| R-HSA-382556 | ABC-family proteins mediated transport | 9.396893e-01 | 0.027 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 9.407330e-01 | 0.027 |
| R-HSA-3560782 | Diseases associated with glycosaminoglycan metabolism | 9.410676e-01 | 0.026 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 9.418390e-01 | 0.026 |
| R-HSA-9733709 | Cardiogenesis | 9.418390e-01 | 0.026 |
| R-HSA-397014 | Muscle contraction | 9.429553e-01 | 0.026 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 9.440096e-01 | 0.025 |
| R-HSA-433692 | Proton-coupled monocarboxylate transport | 9.446272e-01 | 0.025 |
| R-HSA-1839122 | Signaling by activated point mutants of FGFR1 | 9.446272e-01 | 0.025 |
| R-HSA-168330 | Viral RNP Complexes in the Host Cell Nucleus | 9.446272e-01 | 0.025 |
| R-HSA-425561 | Sodium/Calcium exchangers | 9.446272e-01 | 0.025 |
| R-HSA-3772470 | Negative regulation of TCF-dependent signaling by WNT ligand antagonists | 9.446272e-01 | 0.025 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 9.450995e-01 | 0.025 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 9.450995e-01 | 0.025 |
| R-HSA-392851 | Prostacyclin signalling through prostacyclin receptor | 9.450995e-01 | 0.025 |
| R-HSA-2142688 | Synthesis of 5-eicosatetraenoic acids | 9.450995e-01 | 0.025 |
| R-HSA-9834899 | Specification of the neural plate border | 9.450995e-01 | 0.025 |
| R-HSA-9913635 | Strand-asynchronous mitochondrial DNA replication | 9.450995e-01 | 0.025 |
| R-HSA-9694682 | SARS-CoV-2 Genome Replication and Transcription | 9.450995e-01 | 0.025 |
| R-HSA-8874081 | MET activates PTK2 signaling | 9.453763e-01 | 0.024 |
| R-HSA-1855183 | Synthesis of IP2, IP, and Ins in the cytosol | 9.453763e-01 | 0.024 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 9.472709e-01 | 0.024 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 9.472709e-01 | 0.024 |
| R-HSA-597592 | Post-translational protein modification | 9.478003e-01 | 0.023 |
| R-HSA-1482788 | Acyl chain remodelling of PC | 9.488223e-01 | 0.023 |
| R-HSA-8964539 | Glutamate and glutamine metabolism | 9.488223e-01 | 0.023 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 9.525601e-01 | 0.021 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 9.525601e-01 | 0.021 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 9.525601e-01 | 0.021 |
| R-HSA-163210 | Formation of ATP by chemiosmotic coupling | 9.531872e-01 | 0.021 |
| R-HSA-5654221 | Phospholipase C-mediated cascade; FGFR2 | 9.531872e-01 | 0.021 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 9.531872e-01 | 0.021 |
| R-HSA-1482922 | Acyl chain remodelling of PI | 9.531872e-01 | 0.021 |
| R-HSA-140875 | Common Pathway of Fibrin Clot Formation | 9.531872e-01 | 0.021 |
| R-HSA-77111 | Synthesis of Ketone Bodies | 9.531872e-01 | 0.021 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 9.543464e-01 | 0.020 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 9.543464e-01 | 0.020 |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft | 9.543464e-01 | 0.020 |
| R-HSA-418890 | Role of second messengers in netrin-1 signaling | 9.543464e-01 | 0.020 |
| R-HSA-70688 | Proline catabolism | 9.543464e-01 | 0.020 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 9.543464e-01 | 0.020 |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 | 9.543464e-01 | 0.020 |
| R-HSA-77305 | Beta oxidation of palmitoyl-CoA to myristoyl-CoA | 9.543464e-01 | 0.020 |
| R-HSA-1247673 | Erythrocytes take up oxygen and release carbon dioxide | 9.543464e-01 | 0.020 |
| R-HSA-193144 | Estrogen biosynthesis | 9.543464e-01 | 0.020 |
| R-HSA-73943 | Reversal of alkylation damage by DNA dioxygenases | 9.543464e-01 | 0.020 |
| R-HSA-9734767 | Developmental Cell Lineages | 9.546094e-01 | 0.020 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 9.550281e-01 | 0.020 |
| R-HSA-392518 | Signal amplification | 9.550281e-01 | 0.020 |
| R-HSA-5686938 | Regulation of TLR by endogenous ligand | 9.550281e-01 | 0.020 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 9.550281e-01 | 0.020 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 9.550281e-01 | 0.020 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 9.552169e-01 | 0.020 |
| R-HSA-5218859 | Regulated Necrosis | 9.556249e-01 | 0.020 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 9.556249e-01 | 0.020 |
| R-HSA-5620971 | Pyroptosis | 9.588530e-01 | 0.018 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 9.589294e-01 | 0.018 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 9.601277e-01 | 0.018 |
| R-HSA-1482925 | Acyl chain remodelling of PG | 9.601277e-01 | 0.018 |
| R-HSA-140837 | Intrinsic Pathway of Fibrin Clot Formation | 9.601277e-01 | 0.018 |
| R-HSA-1482839 | Acyl chain remodelling of PE | 9.605330e-01 | 0.017 |
| R-HSA-170660 | Adenylate cyclase activating pathway | 9.623602e-01 | 0.017 |
| R-HSA-190375 | FGFR2c ligand binding and activation | 9.623602e-01 | 0.017 |
| R-HSA-190322 | FGFR4 ligand binding and activation | 9.623602e-01 | 0.017 |
| R-HSA-9796292 | Formation of axial mesoderm | 9.623602e-01 | 0.017 |
| R-HSA-5676594 | TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway | 9.623602e-01 | 0.017 |
| R-HSA-9735804 | Diseases of nucleotide metabolism | 9.623602e-01 | 0.017 |
| R-HSA-1839130 | Signaling by activated point mutants of FGFR3 | 9.623602e-01 | 0.017 |
| R-HSA-2033514 | FGFR3 mutant receptor activation | 9.623602e-01 | 0.017 |
| R-HSA-8877330 | RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) | 9.623602e-01 | 0.017 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 9.625124e-01 | 0.017 |
| R-HSA-420092 | Glucagon-type ligand receptors | 9.643558e-01 | 0.016 |
| R-HSA-2022928 | HS-GAG biosynthesis | 9.654074e-01 | 0.015 |
| R-HSA-2022870 | CS-GAG biosynthesis | 9.660746e-01 | 0.015 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 9.660746e-01 | 0.015 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 9.660746e-01 | 0.015 |
| R-HSA-9748787 | Azathioprine ADME | 9.666215e-01 | 0.015 |
| R-HSA-216083 | Integrin cell surface interactions | 9.679740e-01 | 0.014 |
| R-HSA-1663150 | The activation of arylsulfatases | 9.689676e-01 | 0.014 |
| R-HSA-418457 | cGMP effects | 9.689676e-01 | 0.014 |
| R-HSA-190372 | FGFR3c ligand binding and activation | 9.689676e-01 | 0.014 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 9.689676e-01 | 0.014 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 9.689676e-01 | 0.014 |
| R-HSA-173599 | Formation of the active cofactor, UDP-glucuronate | 9.689676e-01 | 0.014 |
| R-HSA-9856872 | Malate-aspartate shuttle | 9.689676e-01 | 0.014 |
| R-HSA-9828642 | Respiratory syncytial virus genome transcription | 9.689676e-01 | 0.014 |
| R-HSA-1482798 | Acyl chain remodeling of CL | 9.689676e-01 | 0.014 |
| R-HSA-417957 | P2Y receptors | 9.689676e-01 | 0.014 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 9.691593e-01 | 0.014 |
| R-HSA-390247 | Beta-oxidation of very long chain fatty acids | 9.697163e-01 | 0.013 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 9.711627e-01 | 0.013 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 9.711627e-01 | 0.013 |
| R-HSA-3238698 | WNT ligand biogenesis and trafficking | 9.711627e-01 | 0.013 |
| R-HSA-375280 | Amine ligand-binding receptors | 9.714294e-01 | 0.013 |
| R-HSA-8979227 | Triglyceride metabolism | 9.730865e-01 | 0.012 |
| R-HSA-1566948 | Elastic fibre formation | 9.735194e-01 | 0.012 |
| R-HSA-170670 | Adenylate cyclase inhibitory pathway | 9.744154e-01 | 0.011 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 9.744154e-01 | 0.011 |
| R-HSA-190239 | FGFR3 ligand binding and activation | 9.744154e-01 | 0.011 |
| R-HSA-1502540 | Signaling by Activin | 9.744154e-01 | 0.011 |
| R-HSA-2142712 | Synthesis of 12-eicosatetraenoic acid derivatives | 9.744154e-01 | 0.011 |
| R-HSA-73942 | DNA Damage Reversal | 9.744154e-01 | 0.011 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 9.751616e-01 | 0.011 |
| R-HSA-74182 | Ketone body metabolism | 9.755102e-01 | 0.011 |
| R-HSA-1855167 | Synthesis of pyrophosphates in the cytosol | 9.755102e-01 | 0.011 |
| R-HSA-190236 | Signaling by FGFR | 9.760062e-01 | 0.011 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 9.768708e-01 | 0.010 |
| R-HSA-71403 | Citric acid cycle (TCA cycle) | 9.783089e-01 | 0.010 |
| R-HSA-2142816 | Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) | 9.789071e-01 | 0.009 |
| R-HSA-5083625 | Defective GALNT3 causes HFTC | 9.789071e-01 | 0.009 |
| R-HSA-168275 | Entry of Influenza Virion into Host Cell via Endocytosis | 9.789071e-01 | 0.009 |
| R-HSA-5083636 | Defective GALNT12 causes CRCS1 | 9.789071e-01 | 0.009 |
| R-HSA-9754706 | Atorvastatin ADME | 9.789071e-01 | 0.009 |
| R-HSA-9733458 | Induction of Cell-Cell Fusion | 9.789071e-01 | 0.009 |
| R-HSA-71262 | Carnitine synthesis | 9.789071e-01 | 0.009 |
| R-HSA-9678110 | Attachment and Entry | 9.789071e-01 | 0.009 |
| R-HSA-168268 | Virus Assembly and Release | 9.789071e-01 | 0.009 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 9.792203e-01 | 0.009 |
| R-HSA-428930 | Thromboxane signalling through TP receptor | 9.792203e-01 | 0.009 |
| R-HSA-9854311 | Maturation of TCA enzymes and regulation of TCA cycle | 9.798199e-01 | 0.009 |
| R-HSA-5609975 | Diseases associated with glycosylation precursor biosynthesis | 9.801549e-01 | 0.009 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 9.809052e-01 | 0.008 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 9.823829e-01 | 0.008 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 9.823829e-01 | 0.008 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 9.823829e-01 | 0.008 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 9.826105e-01 | 0.008 |
| R-HSA-6783984 | Glycine degradation | 9.826105e-01 | 0.008 |
| R-HSA-9027307 | Biosynthesis of maresin-like SPMs | 9.826105e-01 | 0.008 |
| R-HSA-5661270 | Formation of xylulose-5-phosphate | 9.826105e-01 | 0.008 |
| R-HSA-9651496 | Defects of contact activation system (CAS) and kallikrein/kinin system (KKS) | 9.826105e-01 | 0.008 |
| R-HSA-9690406 | Transcriptional regulation of testis differentiation | 9.826105e-01 | 0.008 |
| R-HSA-425410 | Metal ion SLC transporters | 9.828362e-01 | 0.008 |
| R-HSA-390522 | Striated Muscle Contraction | 9.829023e-01 | 0.007 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 9.830030e-01 | 0.007 |
| R-HSA-3000178 | ECM proteoglycans | 9.844527e-01 | 0.007 |
| R-HSA-5619102 | SLC transporter disorders | 9.844554e-01 | 0.007 |
| R-HSA-9683701 | Translation of Structural Proteins | 9.846854e-01 | 0.007 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 9.854729e-01 | 0.006 |
| R-HSA-1483166 | Synthesis of PA | 9.856313e-01 | 0.006 |
| R-HSA-5083632 | Defective C1GALT1C1 causes TNPS | 9.856638e-01 | 0.006 |
| R-HSA-2142770 | Synthesis of 15-eicosatetraenoic acid derivatives | 9.856638e-01 | 0.006 |
| R-HSA-2408550 | Metabolism of ingested H2SeO4 and H2SeO3 into H2Se | 9.856638e-01 | 0.006 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 9.856638e-01 | 0.006 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 9.859815e-01 | 0.006 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 9.866784e-01 | 0.006 |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism | 9.873443e-01 | 0.006 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 9.873661e-01 | 0.006 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 9.873661e-01 | 0.006 |
| R-HSA-8949613 | Cristae formation | 9.873661e-01 | 0.006 |
| R-HSA-264876 | Insulin processing | 9.873661e-01 | 0.006 |
| R-HSA-193807 | Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 9.873661e-01 | 0.006 |
| R-HSA-9828806 | Maturation of hRSV A proteins | 9.873661e-01 | 0.006 |
| R-HSA-418217 | G beta:gamma signalling through PLC beta | 9.881811e-01 | 0.005 |
| R-HSA-2033519 | Activated point mutants of FGFR2 | 9.881811e-01 | 0.005 |
| R-HSA-2142670 | Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) | 9.881811e-01 | 0.005 |
| R-HSA-500657 | Presynaptic function of Kainate receptors | 9.881811e-01 | 0.005 |
| R-HSA-196791 | Vitamin D (calciferol) metabolism | 9.881811e-01 | 0.005 |
| R-HSA-1638091 | Heparan sulfate/heparin (HS-GAG) metabolism | 9.888063e-01 | 0.005 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 9.888063e-01 | 0.005 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 9.891263e-01 | 0.005 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 9.893126e-01 | 0.005 |
| R-HSA-73614 | Pyrimidine salvage | 9.893126e-01 | 0.005 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 9.894276e-01 | 0.005 |
| R-HSA-418555 | G alpha (s) signalling events | 9.894784e-01 | 0.005 |
| R-HSA-418346 | Platelet homeostasis | 9.898541e-01 | 0.004 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 9.902566e-01 | 0.004 |
| R-HSA-500753 | Pyrimidine biosynthesis | 9.902566e-01 | 0.004 |
| R-HSA-1237044 | Erythrocytes take up carbon dioxide and release oxygen | 9.902566e-01 | 0.004 |
| R-HSA-1480926 | O2/CO2 exchange in erythrocytes | 9.902566e-01 | 0.004 |
| R-HSA-1237112 | Methionine salvage pathway | 9.902566e-01 | 0.004 |
| R-HSA-9671793 | Diseases of hemostasis | 9.902566e-01 | 0.004 |
| R-HSA-2243919 | Crosslinking of collagen fibrils | 9.902566e-01 | 0.004 |
| R-HSA-196757 | Metabolism of folate and pterines | 9.906652e-01 | 0.004 |
| R-HSA-1442490 | Collagen degradation | 9.913109e-01 | 0.004 |
| R-HSA-1362409 | Mitochondrial iron-sulfur cluster biogenesis | 9.919676e-01 | 0.004 |
| R-HSA-71288 | Creatine metabolism | 9.919676e-01 | 0.004 |
| R-HSA-9629569 | Protein hydroxylation | 9.919676e-01 | 0.004 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 9.919929e-01 | 0.003 |
| R-HSA-2046106 | alpha-linolenic acid (ALA) metabolism | 9.919929e-01 | 0.003 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 9.921284e-01 | 0.003 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.923338e-01 | 0.003 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 9.923670e-01 | 0.003 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 9.923670e-01 | 0.003 |
| R-HSA-6783783 | Interleukin-10 signaling | 9.930833e-01 | 0.003 |
| R-HSA-5663205 | Infectious disease | 9.930953e-01 | 0.003 |
| R-HSA-72306 | tRNA processing | 9.932508e-01 | 0.003 |
| R-HSA-190241 | FGFR2 ligand binding and activation | 9.933783e-01 | 0.003 |
| R-HSA-8964208 | Phenylalanine metabolism | 9.933783e-01 | 0.003 |
| R-HSA-2161541 | Abacavir metabolism | 9.933783e-01 | 0.003 |
| R-HSA-422085 | Synthesis, secretion, and deacylation of Ghrelin | 9.933783e-01 | 0.003 |
| R-HSA-975634 | Retinoid metabolism and transport | 9.935146e-01 | 0.003 |
| R-HSA-379726 | Mitochondrial tRNA aminoacylation | 9.941221e-01 | 0.003 |
| R-HSA-211979 | Eicosanoids | 9.945413e-01 | 0.002 |
| R-HSA-977347 | Serine metabolism | 9.945413e-01 | 0.002 |
| R-HSA-174403 | Glutathione synthesis and recycling | 9.945413e-01 | 0.002 |
| R-HSA-2022377 | Metabolism of Angiotensinogen to Angiotensins | 9.945413e-01 | 0.002 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 9.949450e-01 | 0.002 |
| R-HSA-5083635 | Defective B3GALTL causes PpS | 9.954133e-01 | 0.002 |
| R-HSA-159418 | Recycling of bile acids and salts | 9.954133e-01 | 0.002 |
| R-HSA-76071 | RNA Polymerase III Transcription Initiation From Type 3 Promoter | 9.955001e-01 | 0.002 |
| R-HSA-975578 | Reactions specific to the complex N-glycan synthesis pathway | 9.955001e-01 | 0.002 |
| R-HSA-71384 | Ethanol oxidation | 9.955001e-01 | 0.002 |
| R-HSA-189200 | Cellular hexose transport | 9.955001e-01 | 0.002 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 9.955001e-01 | 0.002 |
| R-HSA-2024101 | CS/DS degradation | 9.961336e-01 | 0.002 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 9.961336e-01 | 0.002 |
| R-HSA-5223345 | Miscellaneous transport and binding events | 9.961336e-01 | 0.002 |
| R-HSA-189483 | Heme degradation | 9.961336e-01 | 0.002 |
| R-HSA-977068 | Termination of O-glycan biosynthesis | 9.962905e-01 | 0.002 |
| R-HSA-9018682 | Biosynthesis of maresins | 9.962905e-01 | 0.002 |
| R-HSA-446210 | Synthesis of UDP-N-acetyl-glucosamine | 9.962905e-01 | 0.002 |
| R-HSA-9937008 | Mitochondrial mRNA modification | 9.962905e-01 | 0.002 |
| R-HSA-112310 | Neurotransmitter release cycle | 9.964080e-01 | 0.002 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 9.965970e-01 | 0.001 |
| R-HSA-1296071 | Potassium Channels | 9.966333e-01 | 0.001 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 9.967251e-01 | 0.001 |
| R-HSA-203615 | eNOS activation | 9.967425e-01 | 0.001 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 9.968480e-01 | 0.001 |
| R-HSA-73621 | Pyrimidine catabolism | 9.968594e-01 | 0.001 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 9.968594e-01 | 0.001 |
| R-HSA-211999 | CYP2E1 reactions | 9.969421e-01 | 0.001 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 9.969421e-01 | 0.001 |
| R-HSA-446199 | Synthesis of dolichyl-phosphate | 9.969421e-01 | 0.001 |
| R-HSA-5669034 | TNFs bind their physiological receptors | 9.969421e-01 | 0.001 |
| R-HSA-389887 | Beta-oxidation of pristanoyl-CoA | 9.974793e-01 | 0.001 |
| R-HSA-2160916 | Hyaluronan degradation | 9.974793e-01 | 0.001 |
| R-HSA-3296469 | Defects in cobalamin (B12) metabolism | 9.974793e-01 | 0.001 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 9.976910e-01 | 0.001 |
| R-HSA-9845576 | Glycosphingolipid transport | 9.976910e-01 | 0.001 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 9.977132e-01 | 0.001 |
| R-HSA-2046105 | Linoleic acid (LA) metabolism | 9.979221e-01 | 0.001 |
| R-HSA-9638630 | Attachment of bacteria to epithelial cells | 9.979221e-01 | 0.001 |
| R-HSA-70635 | Urea cycle | 9.979221e-01 | 0.001 |
| R-HSA-2161522 | Abacavir ADME | 9.979221e-01 | 0.001 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 9.979221e-01 | 0.001 |
| R-HSA-9753281 | Paracetamol ADME | 9.979839e-01 | 0.001 |
| R-HSA-5173214 | O-glycosylation of TSR domain-containing proteins | 9.980573e-01 | 0.001 |
| R-HSA-549127 | SLC-mediated transport of organic cations | 9.980573e-01 | 0.001 |
| R-HSA-419037 | NCAM1 interactions | 9.980573e-01 | 0.001 |
| R-HSA-168249 | Innate Immune System | 9.981669e-01 | 0.001 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 9.981882e-01 | 0.001 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 9.982651e-01 | 0.001 |
| R-HSA-901032 | ER Quality Control Compartment (ERQC) | 9.982872e-01 | 0.001 |
| R-HSA-2046104 | alpha-linolenic (omega3) and linoleic (omega6) acid metabolism | 9.983388e-01 | 0.001 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.984278e-01 | 0.001 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.984278e-01 | 0.001 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 9.985902e-01 | 0.001 |
| R-HSA-392499 | Metabolism of proteins | 9.986894e-01 | 0.001 |
| R-HSA-1474244 | Extracellular matrix organization | 9.987160e-01 | 0.001 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.987889e-01 | 0.001 |
| R-HSA-389661 | Glyoxylate metabolism and glycine degradation | 9.987959e-01 | 0.001 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 9.988362e-01 | 0.001 |
| R-HSA-1592389 | Activation of Matrix Metalloproteinases | 9.988362e-01 | 0.001 |
| R-HSA-71240 | Tryptophan catabolism | 9.988458e-01 | 0.001 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 9.988908e-01 | 0.000 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 9.989757e-01 | 0.000 |
| R-HSA-112311 | Neurotransmitter clearance | 9.990407e-01 | 0.000 |
| R-HSA-2206281 | Mucopolysaccharidoses | 9.990407e-01 | 0.000 |
| R-HSA-156590 | Glutathione conjugation | 9.990545e-01 | 0.000 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 9.990545e-01 | 0.000 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 9.991231e-01 | 0.000 |
| R-HSA-9864848 | Complex IV assembly | 9.991291e-01 | 0.000 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 9.991855e-01 | 0.000 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 9.991859e-01 | 0.000 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 9.991859e-01 | 0.000 |
| R-HSA-189451 | Heme biosynthesis | 9.991859e-01 | 0.000 |
| R-HSA-162710 | Synthesis of glycosylphosphatidylinositol (GPI) | 9.992093e-01 | 0.000 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 9.992964e-01 | 0.000 |
| R-HSA-8978934 | Metabolism of cofactors | 9.992964e-01 | 0.000 |
| R-HSA-1483257 | Phospholipid metabolism | 9.993495e-01 | 0.000 |
| R-HSA-499943 | Interconversion of nucleotide di- and triphosphates | 9.993925e-01 | 0.000 |
| R-HSA-416476 | G alpha (q) signalling events | 9.994391e-01 | 0.000 |
| R-HSA-6809371 | Formation of the cornified envelope | 9.994805e-01 | 0.000 |
| R-HSA-156581 | Methylation | 9.995190e-01 | 0.000 |
| R-HSA-1614558 | Degradation of cysteine and homocysteine | 9.995967e-01 | 0.000 |
| R-HSA-2142845 | Hyaluronan metabolism | 9.996351e-01 | 0.000 |
| R-HSA-5365859 | RA biosynthesis pathway | 9.996351e-01 | 0.000 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 9.996619e-01 | 0.000 |
| R-HSA-5621480 | Dectin-2 family | 9.996741e-01 | 0.000 |
| R-HSA-2408508 | Metabolism of ingested SeMet, Sec, MeSec into H2Se | 9.996992e-01 | 0.000 |
| R-HSA-2142789 | Ubiquinol biosynthesis | 9.997957e-01 | 0.000 |
| R-HSA-8963691 | Phenylalanine and tyrosine metabolism | 9.997957e-01 | 0.000 |
| R-HSA-1643685 | Disease | 9.998264e-01 | 0.000 |
| R-HSA-189445 | Metabolism of porphyrins | 9.998294e-01 | 0.000 |
| R-HSA-74217 | Purine salvage | 9.998316e-01 | 0.000 |
| R-HSA-9931953 | Biofilm formation | 9.998316e-01 | 0.000 |
| R-HSA-8956321 | Nucleotide salvage | 9.998322e-01 | 0.000 |
| R-HSA-211976 | Endogenous sterols | 9.998322e-01 | 0.000 |
| R-HSA-2162123 | Synthesis of Prostaglandins (PG) and Thromboxanes (TX) | 9.998335e-01 | 0.000 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 9.998440e-01 | 0.000 |
| R-HSA-2514856 | The phototransduction cascade | 9.998606e-01 | 0.000 |
| R-HSA-9648002 | RAS processing | 9.998612e-01 | 0.000 |
| R-HSA-6799198 | Complex I biogenesis | 9.998799e-01 | 0.000 |
| R-HSA-975576 | N-glycan antennae elongation in the medial/trans-Golgi | 9.998856e-01 | 0.000 |
| R-HSA-1222556 | ROS and RNS production in phagocytes | 9.998941e-01 | 0.000 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.998980e-01 | 0.000 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 9.998984e-01 | 0.000 |
| R-HSA-390918 | Peroxisomal lipid metabolism | 9.998998e-01 | 0.000 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 9.999097e-01 | 0.000 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 9.999214e-01 | 0.000 |
| R-HSA-1793185 | Chondroitin sulfate/dermatan sulfate metabolism | 9.999317e-01 | 0.000 |
| R-HSA-991365 | Activation of GABAB receptors | 9.999360e-01 | 0.000 |
| R-HSA-977444 | GABA B receptor activation | 9.999360e-01 | 0.000 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 9.999387e-01 | 0.000 |
| R-HSA-9955298 | SLC-mediated transport of organic anions | 9.999442e-01 | 0.000 |
| R-HSA-1461973 | Defensins | 9.999472e-01 | 0.000 |
| R-HSA-75876 | Synthesis of very long-chain fatty acyl-CoAs | 9.999472e-01 | 0.000 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 9.999525e-01 | 0.000 |
| R-HSA-196741 | Cobalamin (Cbl, vitamin B12) transport and metabolism | 9.999565e-01 | 0.000 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 9.999565e-01 | 0.000 |
| R-HSA-5389840 | Mitochondrial translation elongation | 9.999575e-01 | 0.000 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 9.999631e-01 | 0.000 |
| R-HSA-77286 | mitochondrial fatty acid beta-oxidation of saturated fatty acids | 9.999642e-01 | 0.000 |
| R-HSA-373080 | Class B/2 (Secretin family receptors) | 9.999660e-01 | 0.000 |
| R-HSA-2029481 | FCGR activation | 9.999818e-01 | 0.000 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.999821e-01 | 0.000 |
| R-HSA-380108 | Chemokine receptors bind chemokines | 9.999835e-01 | 0.000 |
| R-HSA-1614635 | Sulfur amino acid metabolism | 9.999871e-01 | 0.000 |
| R-HSA-156584 | Cytosolic sulfonation of small molecules | 9.999888e-01 | 0.000 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 9.999888e-01 | 0.000 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 9.999889e-01 | 0.000 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 9.999919e-01 | 0.000 |
| R-HSA-196807 | Nicotinate metabolism | 9.999921e-01 | 0.000 |
| R-HSA-913709 | O-linked glycosylation of mucins | 9.999934e-01 | 0.000 |
| R-HSA-388396 | GPCR downstream signalling | 9.999935e-01 | 0.000 |
| R-HSA-156588 | Glucuronidation | 9.999937e-01 | 0.000 |
| R-HSA-2980736 | Peptide hormone metabolism | 9.999953e-01 | 0.000 |
| R-HSA-74259 | Purine catabolism | 9.999968e-01 | 0.000 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 9.999968e-01 | 0.000 |
| R-HSA-9749641 | Aspirin ADME | 9.999974e-01 | 0.000 |
| R-HSA-4085001 | Sialic acid metabolism | 9.999976e-01 | 0.000 |
| R-HSA-611105 | Respiratory electron transport | 9.999976e-01 | 0.000 |
| R-HSA-977443 | GABA receptor activation | 9.999980e-01 | 0.000 |
| R-HSA-5368286 | Mitochondrial translation initiation | 9.999987e-01 | 0.000 |
| R-HSA-8963743 | Digestion and absorption | 9.999989e-01 | 0.000 |
| R-HSA-3781865 | Diseases of glycosylation | 9.999989e-01 | 0.000 |
| R-HSA-191273 | Cholesterol biosynthesis | 9.999989e-01 | 0.000 |
| R-HSA-211981 | Xenobiotics | 9.999991e-01 | 0.000 |
| R-HSA-9840309 | Glycosphingolipid biosynthesis | 9.999991e-01 | 0.000 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 9.999994e-01 | 0.000 |
| R-HSA-196071 | Metabolism of steroid hormones | 9.999995e-01 | 0.000 |
| R-HSA-2187338 | Visual phototransduction | 9.999995e-01 | 0.000 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 9.999997e-01 | 0.000 |
| R-HSA-2168880 | Scavenging of heme from plasma | 9.999997e-01 | 0.000 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.999997e-01 | 0.000 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 9.999998e-01 | 0.000 |
| R-HSA-5419276 | Mitochondrial translation termination | 9.999998e-01 | 0.000 |
| R-HSA-173623 | Classical antibody-mediated complement activation | 9.999999e-01 | 0.000 |
| R-HSA-5368287 | Mitochondrial translation | 9.999999e-01 | 0.000 |
| R-HSA-15869 | Metabolism of nucleotides | 9.999999e-01 | 0.000 |
| R-HSA-375276 | Peptide ligand-binding receptors | 9.999999e-01 | 0.000 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.999999e-01 | 0.000 |
| R-HSA-418594 | G alpha (i) signalling events | 9.999999e-01 | 0.000 |
| R-HSA-5579029 | Metabolic disorders of biological oxidation enzymes | 1.000000e+00 | 0.000 |
| R-HSA-163125 | Post-translational modification: synthesis of GPI-anchored proteins | 1.000000e+00 | 0.000 |
| R-HSA-372790 | Signaling by GPCR | 1.000000e+00 | 0.000 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 1.000000e+00 | 0.000 |
| R-HSA-8956319 | Nucleotide catabolism | 1.000000e+00 | 0.000 |
| R-HSA-8957322 | Metabolism of steroids | 1.000000e+00 | 0.000 |
| R-HSA-2142753 | Arachidonate metabolism | 1.000000e+00 | 0.000 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-5173105 | O-linked glycosylation | 1.000000e+00 | 0.000 |
| R-HSA-6805567 | Keratinization | 1.000000e+00 | 0.000 |
| R-HSA-166786 | Creation of C4 and C2 activators | 1.000000e+00 | 0.000 |
| R-HSA-9748784 | Drug ADME | 1.000000e+00 | 0.000 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 1.000000e+00 | 0.000 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 1.000000e+00 | 0.000 |
| R-HSA-6803157 | Antimicrobial peptides | 1.000000e+00 | 0.000 |
| R-HSA-977606 | Regulation of Complement cascade | 1.000000e+00 | 0.000 |
| R-HSA-166663 | Initial triggering of complement | 1.000000e+00 | 0.000 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 1.000000e+00 | 0.000 |
| R-HSA-9717189 | Sensory perception of taste | 1.000000e+00 | 0.000 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 1.000000e+00 | 0.000 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 1.000000e+00 | 0.000 |
| R-HSA-9717207 | Sensory perception of sweet, bitter, and umami (glutamate) taste | 1.000000e+00 | 0.000 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 1.000000e+00 | 0.000 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 1.000000e+00 | 0.000 |
| R-HSA-428157 | Sphingolipid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 1.000000e+00 | 0.000 |
| R-HSA-166658 | Complement cascade | 1.000000e+00 | 0.000 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 1.000000e+00 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 1.000000e+00 | 0.000 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 1.000000e+00 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 1.000000e+00 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 1.000000e+00 | 0.000 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 1.000000e+00 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 1.000000e+00 | 0.000 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 1.000000e+00 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | -0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | -0.000 |
| R-HSA-500792 | GPCR ligand binding | 1.000000e+00 | -0.000 |
| R-HSA-211859 | Biological oxidations | 1.000000e+00 | -0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | -0.000 |
| R-HSA-9824439 | Bacterial Infection Pathways | 1.000000e+00 | -0.000 |
| R-HSA-9640148 | Infection with Enterobacteria | 1.000000e+00 | -0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
COT |
0.868 | 0.136 | 2 | 0.901 |
MTOR |
0.864 | 0.360 | 1 | 0.826 |
MST4 |
0.857 | 0.240 | 2 | 0.909 |
CLK3 |
0.856 | 0.108 | 1 | 0.828 |
NDR2 |
0.856 | 0.132 | -3 | 0.868 |
CDC7 |
0.856 | 0.061 | 1 | 0.854 |
PRPK |
0.852 | 0.048 | -1 | 0.404 |
PIM3 |
0.852 | 0.055 | -3 | 0.867 |
MARK4 |
0.851 | 0.250 | 4 | 0.883 |
NIM1 |
0.850 | 0.359 | 3 | 0.821 |
CDKL1 |
0.850 | 0.123 | -3 | 0.837 |
RAF1 |
0.849 | 0.033 | 1 | 0.897 |
MOS |
0.849 | 0.029 | 1 | 0.889 |
GCN2 |
0.848 | -0.029 | 2 | 0.837 |
PKCD |
0.848 | 0.161 | 2 | 0.836 |
PRKD1 |
0.847 | 0.065 | -3 | 0.856 |
DSTYK |
0.847 | -0.006 | 2 | 0.918 |
WNK1 |
0.847 | 0.073 | -2 | 0.925 |
TBK1 |
0.847 | -0.002 | 1 | 0.815 |
NDR1 |
0.846 | 0.090 | -3 | 0.863 |
ULK2 |
0.846 | 0.004 | 2 | 0.818 |
NLK |
0.846 | 0.022 | 1 | 0.842 |
CDKL5 |
0.846 | 0.092 | -3 | 0.829 |
PDHK4 |
0.845 | 0.003 | 1 | 0.895 |
NUAK2 |
0.845 | 0.096 | -3 | 0.868 |
RSK2 |
0.845 | 0.073 | -3 | 0.803 |
NEK6 |
0.845 | 0.000 | -2 | 0.913 |
IKKB |
0.844 | -0.089 | -2 | 0.800 |
CAMK1B |
0.843 | 0.018 | -3 | 0.891 |
ATR |
0.843 | 0.042 | 1 | 0.857 |
BCKDK |
0.843 | 0.031 | -1 | 0.407 |
BMPR2 |
0.843 | -0.063 | -2 | 0.933 |
PKN3 |
0.843 | 0.051 | -3 | 0.859 |
PDHK1 |
0.842 | -0.006 | 1 | 0.896 |
PIM1 |
0.842 | 0.074 | -3 | 0.813 |
AMPKA1 |
0.842 | 0.098 | -3 | 0.880 |
SRPK1 |
0.842 | 0.067 | -3 | 0.787 |
IKKE |
0.842 | -0.036 | 1 | 0.811 |
ERK5 |
0.842 | 0.018 | 1 | 0.821 |
PKN2 |
0.841 | 0.086 | -3 | 0.867 |
P90RSK |
0.841 | 0.060 | -3 | 0.808 |
PRKD2 |
0.841 | 0.037 | -3 | 0.799 |
TGFBR2 |
0.841 | -0.005 | -2 | 0.848 |
NIK |
0.841 | 0.061 | -3 | 0.908 |
RSK3 |
0.841 | 0.066 | -3 | 0.798 |
PKCA |
0.841 | 0.187 | 2 | 0.783 |
SKMLCK |
0.841 | 0.044 | -2 | 0.903 |
HIPK4 |
0.840 | 0.061 | 1 | 0.793 |
QSK |
0.840 | 0.216 | 4 | 0.862 |
NEK7 |
0.839 | -0.064 | -3 | 0.872 |
ICK |
0.839 | 0.084 | -3 | 0.871 |
CAMK2G |
0.838 | -0.047 | 2 | 0.837 |
LATS2 |
0.837 | 0.024 | -5 | 0.791 |
PKACG |
0.837 | 0.059 | -2 | 0.781 |
TSSK1 |
0.837 | 0.075 | -3 | 0.898 |
PKCG |
0.837 | 0.139 | 2 | 0.788 |
CAMK2D |
0.837 | 0.044 | -3 | 0.869 |
MLK1 |
0.836 | -0.067 | 2 | 0.860 |
CHAK2 |
0.836 | -0.057 | -1 | 0.336 |
PKCB |
0.836 | 0.123 | 2 | 0.792 |
AMPKA2 |
0.836 | 0.083 | -3 | 0.847 |
CAMLCK |
0.836 | 0.012 | -2 | 0.895 |
AURC |
0.836 | 0.043 | -2 | 0.689 |
SIK |
0.836 | 0.190 | -3 | 0.785 |
KIS |
0.835 | 0.047 | 1 | 0.688 |
RIPK3 |
0.835 | -0.086 | 3 | 0.789 |
QIK |
0.835 | 0.182 | -3 | 0.859 |
NEK9 |
0.835 | -0.018 | 2 | 0.880 |
DAPK2 |
0.834 | 0.016 | -3 | 0.897 |
MNK2 |
0.834 | 0.051 | -2 | 0.831 |
IKKA |
0.833 | -0.035 | -2 | 0.791 |
IRE1 |
0.833 | 0.002 | 1 | 0.836 |
HUNK |
0.833 | -0.040 | 2 | 0.827 |
CDK18 |
0.833 | 0.107 | 1 | 0.591 |
SRPK2 |
0.832 | 0.054 | -3 | 0.708 |
GRK5 |
0.832 | -0.105 | -3 | 0.886 |
CDK8 |
0.832 | 0.043 | 1 | 0.653 |
WNK3 |
0.832 | -0.118 | 1 | 0.870 |
MASTL |
0.831 | 0.003 | -2 | 0.868 |
DNAPK |
0.831 | 0.137 | 1 | 0.762 |
P70S6KB |
0.831 | 0.007 | -3 | 0.825 |
MAPKAPK3 |
0.831 | -0.021 | -3 | 0.804 |
FAM20C |
0.831 | 0.045 | 2 | 0.610 |
CDK5 |
0.831 | 0.107 | 1 | 0.683 |
GRK1 |
0.831 | -0.021 | -2 | 0.831 |
PKCZ |
0.830 | 0.066 | 2 | 0.825 |
MARK3 |
0.830 | 0.171 | 4 | 0.821 |
ULK1 |
0.830 | -0.103 | -3 | 0.846 |
SGK3 |
0.830 | 0.123 | -3 | 0.793 |
TSSK2 |
0.830 | 0.001 | -5 | 0.886 |
LATS1 |
0.830 | 0.077 | -3 | 0.881 |
MLK2 |
0.829 | -0.057 | 2 | 0.860 |
CDK19 |
0.829 | 0.054 | 1 | 0.612 |
NUAK1 |
0.829 | 0.040 | -3 | 0.814 |
PKACB |
0.829 | 0.087 | -2 | 0.706 |
PKR |
0.829 | 0.026 | 1 | 0.883 |
ATM |
0.828 | -0.008 | 1 | 0.796 |
MLK3 |
0.828 | -0.021 | 2 | 0.795 |
SRPK3 |
0.828 | 0.053 | -3 | 0.758 |
CDK7 |
0.828 | 0.013 | 1 | 0.663 |
MPSK1 |
0.828 | 0.253 | 1 | 0.843 |
RSK4 |
0.828 | 0.058 | -3 | 0.772 |
MAPKAPK2 |
0.827 | 0.011 | -3 | 0.759 |
NEK2 |
0.827 | 0.024 | 2 | 0.857 |
RIPK1 |
0.827 | -0.093 | 1 | 0.859 |
MARK2 |
0.827 | 0.163 | 4 | 0.786 |
MNK1 |
0.826 | 0.046 | -2 | 0.840 |
PKCH |
0.826 | 0.075 | 2 | 0.772 |
BMPR1B |
0.826 | 0.030 | 1 | 0.795 |
DYRK2 |
0.826 | 0.042 | 1 | 0.690 |
CAMK2B |
0.826 | 0.025 | 2 | 0.804 |
PAK1 |
0.826 | -0.001 | -2 | 0.821 |
CLK2 |
0.826 | 0.119 | -3 | 0.780 |
ANKRD3 |
0.826 | -0.113 | 1 | 0.901 |
GRK7 |
0.826 | 0.083 | 1 | 0.789 |
CLK1 |
0.825 | 0.057 | -3 | 0.773 |
IRE2 |
0.825 | -0.004 | 2 | 0.788 |
MSK2 |
0.825 | 0.016 | -3 | 0.775 |
CLK4 |
0.825 | 0.047 | -3 | 0.797 |
GRK6 |
0.825 | -0.083 | 1 | 0.858 |
CDK13 |
0.825 | 0.037 | 1 | 0.637 |
PRKD3 |
0.825 | 0.006 | -3 | 0.772 |
PHKG1 |
0.824 | -0.005 | -3 | 0.853 |
MELK |
0.824 | -0.012 | -3 | 0.831 |
PAK3 |
0.824 | -0.026 | -2 | 0.820 |
AKT2 |
0.823 | 0.065 | -3 | 0.718 |
YSK4 |
0.823 | -0.015 | 1 | 0.833 |
TGFBR1 |
0.823 | 0.010 | -2 | 0.855 |
DLK |
0.823 | -0.154 | 1 | 0.861 |
MST3 |
0.823 | 0.184 | 2 | 0.886 |
CDK1 |
0.823 | 0.053 | 1 | 0.608 |
PLK4 |
0.823 | 0.105 | 2 | 0.642 |
P38A |
0.822 | 0.062 | 1 | 0.703 |
GRK4 |
0.822 | -0.111 | -2 | 0.868 |
AURB |
0.822 | 0.012 | -2 | 0.687 |
PRKX |
0.822 | 0.079 | -3 | 0.705 |
PAK6 |
0.822 | 0.013 | -2 | 0.743 |
ALK4 |
0.822 | -0.033 | -2 | 0.885 |
DCAMKL1 |
0.822 | 0.102 | -3 | 0.811 |
TAO3 |
0.822 | 0.191 | 1 | 0.842 |
TTBK2 |
0.821 | -0.125 | 2 | 0.732 |
HIPK1 |
0.821 | 0.065 | 1 | 0.712 |
MEK1 |
0.821 | 0.013 | 2 | 0.862 |
CAMK4 |
0.821 | -0.063 | -3 | 0.844 |
MARK1 |
0.821 | 0.138 | 4 | 0.840 |
PKCT |
0.821 | 0.100 | 2 | 0.781 |
CAMK2A |
0.820 | -0.005 | 2 | 0.825 |
JNK2 |
0.820 | 0.048 | 1 | 0.606 |
CDK17 |
0.820 | 0.067 | 1 | 0.529 |
PIM2 |
0.820 | 0.047 | -3 | 0.775 |
SMG1 |
0.820 | -0.049 | 1 | 0.812 |
VRK2 |
0.820 | -0.040 | 1 | 0.900 |
CDK12 |
0.820 | 0.044 | 1 | 0.608 |
WNK4 |
0.820 | 0.043 | -2 | 0.923 |
PKG2 |
0.819 | 0.009 | -2 | 0.709 |
MLK4 |
0.819 | -0.069 | 2 | 0.768 |
MSK1 |
0.819 | 0.018 | -3 | 0.779 |
BRSK2 |
0.819 | 0.012 | -3 | 0.841 |
HIPK2 |
0.819 | 0.052 | 1 | 0.596 |
CDK14 |
0.818 | 0.094 | 1 | 0.643 |
BRSK1 |
0.818 | 0.014 | -3 | 0.818 |
TLK2 |
0.818 | -0.031 | 1 | 0.835 |
PLK1 |
0.817 | -0.101 | -2 | 0.856 |
CHAK1 |
0.817 | -0.105 | 2 | 0.810 |
CHK1 |
0.817 | 0.001 | -3 | 0.847 |
P38B |
0.817 | 0.047 | 1 | 0.623 |
JNK3 |
0.816 | 0.024 | 1 | 0.641 |
AKT1 |
0.816 | 0.077 | -3 | 0.735 |
CDK3 |
0.816 | 0.078 | 1 | 0.549 |
MEKK1 |
0.816 | 0.039 | 1 | 0.861 |
ACVR2A |
0.816 | -0.040 | -2 | 0.840 |
CDK16 |
0.816 | 0.093 | 1 | 0.551 |
ERK1 |
0.816 | 0.021 | 1 | 0.617 |
CDK9 |
0.815 | 0.016 | 1 | 0.647 |
MEKK2 |
0.815 | 0.081 | 2 | 0.840 |
PAK2 |
0.815 | -0.041 | -2 | 0.808 |
CDK2 |
0.815 | 0.032 | 1 | 0.698 |
ALK2 |
0.815 | -0.029 | -2 | 0.862 |
NEK5 |
0.815 | 0.016 | 1 | 0.881 |
ZAK |
0.815 | 0.018 | 1 | 0.826 |
ACVR2B |
0.815 | -0.044 | -2 | 0.851 |
PKCI |
0.814 | 0.072 | 2 | 0.796 |
P38G |
0.814 | 0.037 | 1 | 0.522 |
MYLK4 |
0.814 | -0.030 | -2 | 0.805 |
IRAK4 |
0.814 | -0.037 | 1 | 0.852 |
AURA |
0.813 | 0.005 | -2 | 0.656 |
BRAF |
0.813 | -0.016 | -4 | 0.857 |
PERK |
0.813 | -0.091 | -2 | 0.887 |
HRI |
0.813 | -0.106 | -2 | 0.900 |
PRP4 |
0.812 | 0.031 | -3 | 0.838 |
PKACA |
0.812 | 0.059 | -2 | 0.652 |
CDK10 |
0.812 | 0.069 | 1 | 0.626 |
TNIK |
0.812 | 0.202 | 3 | 0.914 |
HIPK3 |
0.812 | 0.031 | 1 | 0.721 |
PKCE |
0.812 | 0.099 | 2 | 0.775 |
MEK5 |
0.811 | -0.032 | 2 | 0.857 |
MEKK3 |
0.811 | -0.021 | 1 | 0.847 |
DYRK1A |
0.811 | 0.024 | 1 | 0.734 |
HGK |
0.810 | 0.168 | 3 | 0.910 |
CAMK1G |
0.810 | -0.010 | -3 | 0.788 |
PLK3 |
0.810 | -0.091 | 2 | 0.783 |
PHKG2 |
0.810 | 0.011 | -3 | 0.821 |
TAO2 |
0.810 | 0.096 | 2 | 0.890 |
GCK |
0.809 | 0.167 | 1 | 0.857 |
DRAK1 |
0.809 | -0.061 | 1 | 0.777 |
MAK |
0.809 | 0.133 | -2 | 0.800 |
MINK |
0.809 | 0.184 | 1 | 0.861 |
DCAMKL2 |
0.808 | 0.023 | -3 | 0.833 |
ERK2 |
0.808 | -0.030 | 1 | 0.662 |
CK1E |
0.807 | 0.005 | -3 | 0.578 |
KHS2 |
0.807 | 0.211 | 1 | 0.860 |
KHS1 |
0.807 | 0.205 | 1 | 0.853 |
HPK1 |
0.807 | 0.171 | 1 | 0.848 |
MAP3K15 |
0.806 | 0.195 | 1 | 0.816 |
MEKK6 |
0.806 | 0.167 | 1 | 0.841 |
DYRK3 |
0.806 | 0.038 | 1 | 0.717 |
BMPR1A |
0.806 | -0.005 | 1 | 0.774 |
NEK11 |
0.806 | 0.060 | 1 | 0.843 |
SNRK |
0.806 | -0.110 | 2 | 0.702 |
NEK4 |
0.806 | 0.070 | 1 | 0.859 |
GAK |
0.806 | 0.065 | 1 | 0.900 |
PINK1 |
0.805 | -0.092 | 1 | 0.849 |
SMMLCK |
0.805 | -0.008 | -3 | 0.847 |
DYRK4 |
0.805 | 0.032 | 1 | 0.606 |
MAPKAPK5 |
0.805 | -0.097 | -3 | 0.751 |
CK1G1 |
0.805 | 0.029 | -3 | 0.571 |
SSTK |
0.805 | -0.026 | 4 | 0.852 |
PDK1 |
0.804 | 0.062 | 1 | 0.847 |
AKT3 |
0.804 | 0.069 | -3 | 0.656 |
DYRK1B |
0.804 | 0.020 | 1 | 0.640 |
SGK1 |
0.803 | 0.091 | -3 | 0.639 |
P70S6K |
0.803 | -0.019 | -3 | 0.736 |
EEF2K |
0.803 | 0.064 | 3 | 0.890 |
P38D |
0.803 | 0.020 | 1 | 0.550 |
NEK1 |
0.802 | 0.108 | 1 | 0.861 |
LKB1 |
0.802 | -0.008 | -3 | 0.872 |
PAK5 |
0.802 | -0.013 | -2 | 0.678 |
PASK |
0.802 | -0.039 | -3 | 0.884 |
GRK2 |
0.802 | -0.078 | -2 | 0.757 |
TLK1 |
0.802 | -0.115 | -2 | 0.873 |
MST2 |
0.802 | 0.058 | 1 | 0.863 |
YSK1 |
0.801 | 0.175 | 2 | 0.861 |
ERK7 |
0.801 | 0.023 | 2 | 0.598 |
PKN1 |
0.800 | 0.029 | -3 | 0.753 |
NEK8 |
0.800 | -0.098 | 2 | 0.859 |
CAMKK1 |
0.800 | -0.094 | -2 | 0.807 |
GSK3A |
0.800 | 0.036 | 4 | 0.459 |
MOK |
0.800 | 0.091 | 1 | 0.733 |
IRAK1 |
0.799 | -0.162 | -1 | 0.310 |
ROCK2 |
0.799 | 0.070 | -3 | 0.815 |
CDK6 |
0.799 | 0.042 | 1 | 0.624 |
CAMK1D |
0.799 | -0.007 | -3 | 0.710 |
GSK3B |
0.798 | -0.002 | 4 | 0.450 |
LRRK2 |
0.798 | 0.029 | 2 | 0.884 |
LOK |
0.798 | -0.001 | -2 | 0.818 |
DAPK3 |
0.797 | 0.011 | -3 | 0.827 |
MRCKB |
0.797 | 0.038 | -3 | 0.764 |
PBK |
0.797 | 0.097 | 1 | 0.839 |
CAMKK2 |
0.796 | -0.082 | -2 | 0.806 |
PAK4 |
0.796 | -0.019 | -2 | 0.682 |
CK1D |
0.796 | -0.004 | -3 | 0.526 |
TAK1 |
0.795 | -0.071 | 1 | 0.875 |
TTBK1 |
0.795 | -0.143 | 2 | 0.646 |
BUB1 |
0.794 | 0.030 | -5 | 0.836 |
MRCKA |
0.794 | 0.035 | -3 | 0.780 |
MST1 |
0.793 | 0.026 | 1 | 0.852 |
CDK4 |
0.793 | 0.016 | 1 | 0.595 |
CK1A2 |
0.793 | -0.006 | -3 | 0.525 |
CHK2 |
0.792 | 0.001 | -3 | 0.662 |
NEK3 |
0.791 | 0.054 | 1 | 0.817 |
CK2A2 |
0.791 | -0.012 | 1 | 0.702 |
JNK1 |
0.791 | 0.006 | 1 | 0.587 |
VRK1 |
0.790 | -0.087 | 2 | 0.862 |
HASPIN |
0.789 | -0.012 | -1 | 0.322 |
MYO3B |
0.789 | 0.136 | 2 | 0.871 |
SLK |
0.789 | -0.059 | -2 | 0.764 |
DAPK1 |
0.788 | -0.008 | -3 | 0.811 |
MEK2 |
0.788 | -0.019 | 2 | 0.836 |
DMPK1 |
0.788 | 0.062 | -3 | 0.786 |
CAMK1A |
0.788 | 0.000 | -3 | 0.680 |
GRK3 |
0.788 | -0.072 | -2 | 0.710 |
SBK |
0.785 | 0.034 | -3 | 0.596 |
ROCK1 |
0.785 | 0.048 | -3 | 0.780 |
PLK2 |
0.784 | -0.056 | -3 | 0.816 |
STK33 |
0.784 | -0.103 | 2 | 0.636 |
PDHK3_TYR |
0.783 | 0.111 | 4 | 0.928 |
TAO1 |
0.783 | 0.068 | 1 | 0.785 |
MYO3A |
0.782 | 0.123 | 1 | 0.841 |
PKMYT1_TYR |
0.781 | 0.296 | 3 | 0.889 |
RIPK2 |
0.780 | -0.163 | 1 | 0.795 |
CRIK |
0.780 | 0.037 | -3 | 0.734 |
BIKE |
0.779 | 0.060 | 1 | 0.798 |
OSR1 |
0.779 | -0.028 | 2 | 0.839 |
TTK |
0.779 | -0.026 | -2 | 0.867 |
PKG1 |
0.779 | -0.022 | -2 | 0.622 |
CK2A1 |
0.778 | -0.030 | 1 | 0.678 |
MAP2K4_TYR |
0.778 | 0.182 | -1 | 0.434 |
ASK1 |
0.777 | 0.051 | 1 | 0.803 |
TESK1_TYR |
0.775 | 0.004 | 3 | 0.921 |
LIMK2_TYR |
0.773 | 0.068 | -3 | 0.919 |
PDHK4_TYR |
0.773 | 0.040 | 2 | 0.904 |
MAP2K7_TYR |
0.773 | 0.074 | 2 | 0.885 |
MAP2K6_TYR |
0.773 | 0.051 | -1 | 0.412 |
BMPR2_TYR |
0.770 | 0.007 | -1 | 0.405 |
AAK1 |
0.770 | 0.111 | 1 | 0.698 |
PINK1_TYR |
0.768 | -0.039 | 1 | 0.868 |
ALPHAK3 |
0.767 | -0.087 | -1 | 0.327 |
PDHK1_TYR |
0.766 | -0.067 | -1 | 0.386 |
LIMK1_TYR |
0.766 | 0.027 | 2 | 0.884 |
TYK2 |
0.765 | -0.006 | 1 | 0.856 |
YANK3 |
0.763 | -0.036 | 2 | 0.411 |
EPHA6 |
0.761 | -0.106 | -1 | 0.323 |
ROS1 |
0.761 | -0.050 | 3 | 0.812 |
ABL2 |
0.761 | -0.058 | -1 | 0.320 |
RET |
0.761 | -0.141 | 1 | 0.851 |
JAK2 |
0.760 | -0.041 | 1 | 0.848 |
TNNI3K_TYR |
0.760 | 0.061 | 1 | 0.853 |
MST1R |
0.759 | -0.114 | 3 | 0.846 |
JAK1 |
0.759 | 0.069 | 1 | 0.805 |
TYRO3 |
0.759 | -0.130 | 3 | 0.838 |
EPHB4 |
0.759 | -0.124 | -1 | 0.314 |
TXK |
0.758 | -0.047 | 1 | 0.841 |
ABL1 |
0.758 | -0.063 | -1 | 0.322 |
CSF1R |
0.757 | -0.088 | 3 | 0.824 |
YES1 |
0.757 | -0.070 | -1 | 0.347 |
NEK10_TYR |
0.756 | 0.001 | 1 | 0.740 |
LCK |
0.755 | -0.054 | -1 | 0.314 |
FGR |
0.755 | -0.095 | 1 | 0.891 |
TNK2 |
0.755 | -0.058 | 3 | 0.785 |
STLK3 |
0.754 | -0.137 | 1 | 0.799 |
HCK |
0.754 | -0.104 | -1 | 0.320 |
TNK1 |
0.754 | -0.019 | 3 | 0.816 |
CK1A |
0.754 | -0.031 | -3 | 0.433 |
BLK |
0.754 | -0.030 | -1 | 0.323 |
JAK3 |
0.752 | -0.127 | 1 | 0.822 |
ITK |
0.752 | -0.105 | -1 | 0.307 |
DDR1 |
0.752 | -0.149 | 4 | 0.848 |
WEE1_TYR |
0.751 | -0.062 | -1 | 0.317 |
FER |
0.751 | -0.170 | 1 | 0.888 |
BMX |
0.749 | -0.103 | -1 | 0.271 |
INSRR |
0.748 | -0.137 | 3 | 0.781 |
SRMS |
0.748 | -0.152 | 1 | 0.867 |
TEC |
0.748 | -0.122 | -1 | 0.282 |
PDGFRB |
0.747 | -0.153 | 3 | 0.840 |
KIT |
0.746 | -0.144 | 3 | 0.823 |
EPHA4 |
0.746 | -0.115 | 2 | 0.782 |
KDR |
0.746 | -0.114 | 3 | 0.789 |
AXL |
0.745 | -0.155 | 3 | 0.804 |
FLT3 |
0.745 | -0.139 | 3 | 0.833 |
EPHB3 |
0.745 | -0.162 | -1 | 0.295 |
MERTK |
0.745 | -0.137 | 3 | 0.802 |
BTK |
0.745 | -0.180 | -1 | 0.293 |
EPHB1 |
0.744 | -0.185 | 1 | 0.863 |
FYN |
0.744 | -0.069 | -1 | 0.310 |
EPHB2 |
0.744 | -0.155 | -1 | 0.291 |
PTK6 |
0.743 | -0.183 | -1 | 0.279 |
FGFR2 |
0.743 | -0.183 | 3 | 0.822 |
MET |
0.741 | -0.142 | 3 | 0.812 |
PDGFRA |
0.740 | -0.168 | 3 | 0.839 |
FGFR1 |
0.739 | -0.171 | 3 | 0.795 |
TEK |
0.739 | -0.179 | 3 | 0.765 |
LTK |
0.739 | -0.158 | 3 | 0.770 |
LYN |
0.739 | -0.111 | 3 | 0.750 |
ALK |
0.738 | -0.170 | 3 | 0.748 |
EPHA1 |
0.737 | -0.156 | 3 | 0.790 |
FLT1 |
0.736 | -0.160 | -1 | 0.314 |
FRK |
0.736 | -0.142 | -1 | 0.311 |
NTRK1 |
0.736 | -0.186 | -1 | 0.327 |
EPHA7 |
0.736 | -0.146 | 2 | 0.785 |
EPHA3 |
0.734 | -0.168 | 2 | 0.757 |
MATK |
0.734 | -0.130 | -1 | 0.287 |
SRC |
0.734 | -0.098 | -1 | 0.319 |
ERBB2 |
0.733 | -0.166 | 1 | 0.799 |
NTRK3 |
0.733 | -0.149 | -1 | 0.302 |
NTRK2 |
0.733 | -0.196 | 3 | 0.787 |
PTK2B |
0.733 | -0.124 | -1 | 0.298 |
INSR |
0.733 | -0.160 | 3 | 0.762 |
CK1G3 |
0.733 | -0.043 | -3 | 0.384 |
DDR2 |
0.732 | -0.083 | 3 | 0.763 |
FGFR3 |
0.730 | -0.189 | 3 | 0.794 |
FLT4 |
0.730 | -0.191 | 3 | 0.783 |
YANK2 |
0.729 | -0.053 | 2 | 0.427 |
EPHA5 |
0.728 | -0.158 | 2 | 0.763 |
PTK2 |
0.727 | -0.089 | -1 | 0.304 |
EGFR |
0.727 | -0.118 | 1 | 0.701 |
CSK |
0.726 | -0.157 | 2 | 0.790 |
EPHA8 |
0.726 | -0.156 | -1 | 0.287 |
FGFR4 |
0.725 | -0.134 | -1 | 0.294 |
SYK |
0.722 | -0.111 | -1 | 0.282 |
MUSK |
0.721 | -0.140 | 1 | 0.697 |
EPHA2 |
0.717 | -0.159 | -1 | 0.268 |
IGF1R |
0.716 | -0.161 | 3 | 0.696 |
ERBB4 |
0.710 | -0.115 | 1 | 0.707 |
ZAP70 |
0.708 | -0.081 | -1 | 0.280 |
FES |
0.708 | -0.162 | -1 | 0.265 |
CK1G2 |
0.708 | -0.067 | -3 | 0.483 |