Motif 1090 (n=1,722)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A1B0GVI7 | None | T351 | ochoa | Aryl hydrocarbon receptor | None |
| A6NEC2 | NPEPPSL1 | T136 | ochoa | Puromycin-sensitive aminopeptidase-like protein (EC 3.4.11.-) | Aminopeptidase with broad substrate specificity to several peptides. {ECO:0000250}. |
| A6NFI3 | ZNF316 | T533 | ochoa | Zinc finger protein 316 | May be involved in transcriptional regulation. {ECO:0000250}. |
| K7ELQ4 | ATF7-NPFF | T55 | ochoa | ATF7-NPFF readthrough | None |
| O00192 | ARVCF | T903 | 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}. |
| O00401 | WASL | T171 | 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}. |
| O00410 | IPO5 | T645 | ochoa | Importin-5 (Imp5) (Importin subunit beta-3) (Karyopherin beta-3) (Ran-binding protein 5) (RanBP5) | 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). Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607, PubMed:9687515). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. Binds to CPEB3 and mediates its nuclear import following neuronal stimulation (By similarity). In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000250|UniProtKB:Q8BKC5, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9687515}. |
| O00429 | DNM1L | T595 | 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}. |
| O00560 | SDCBP | T200 | psp | Syntenin-1 (Melanoma differentiation-associated protein 9) (MDA-9) (Pro-TGF-alpha cytoplasmic domain-interacting protein 18) (TACIP18) (Scaffold protein Pbp1) (Syndecan-binding protein 1) | Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:11498591, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:26539120, ECO:0000303|PubMed:26291527}. |
| O00750 | PIK3C2B | T90 | 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 | T590 | 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. |
| O14578 | CIT | T307 | 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}. |
| O14668 | PRRG1 | T171 | ochoa | Transmembrane gamma-carboxyglutamic acid protein 1 (Proline-rich gamma-carboxyglutamic acid protein 1) (Proline-rich Gla protein 1) | None |
| O14686 | KMT2D | T1843 | 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 | T2971 | 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}. |
| O14818 | PSMA7 | T152 | 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}. |
| O14939 | PLD2 | T99 | psp | 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}. |
| O14939 | PLD2 | T566 | psp | 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}. |
| O14983 | ATP2A1 | T533 | 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}. |
| O15047 | SETD1A | T554 | 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 | T408 | 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 | T23 | 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}. |
| O15195 | VILL | T129 | ochoa | Villin-like protein | Possible tumor suppressor. |
| O15234 | CASC3 | T357 | 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}. |
| O15409 | FOXP2 | T336 | ochoa | Forkhead box protein P2 (CAG repeat protein 44) (Trinucleotide repeat-containing gene 10 protein) | Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. Involved in neural mechanisms mediating the development of speech and language. |
| O15438 | ABCC3 | T887 | ochoa | ATP-binding cassette sub-family C member 3 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (Canalicular multispecific organic anion transporter 2) (Multi-specific organic anion transporter D) (MOAT-D) (Multidrug resistance-associated protein 3) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266). {ECO:0000250|UniProtKB:O88563, ECO:0000269|PubMed:10359813, ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:15083066, ECO:0000305|PubMed:35307651}. |
| O15446 | POLR1G | T171 | 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}. |
| O43182 | ARHGAP6 | T741 | 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}. |
| O43312 | MTSS1 | T595 | ochoa | Protein MTSS 1 (Metastasis suppressor YGL-1) (Metastasis suppressor protein 1) (Missing in metastasis protein) | May be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton. |
| O43318 | MAP3K7 | T184 | 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}. |
| O43399 | TPD52L2 | T173 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43741 | PRKAB2 | T40 | 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). |
| O43822 | CFAP410 | T102 | ochoa | Cilia- and flagella-associated protein 410 (C21orf-HUMF09G8.5) (Leucine-rich repeat-containing protein 76) (YF5/A2) | Plays a role in cilia formation and/or maintenance (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). Involved in DNA damage repair (PubMed:26290490). {ECO:0000250|UniProtKB:Q8C6G1, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:26290490}. |
| O43930 | PRKY | T201 | ochoa | Putative serine/threonine-protein kinase PRKY (EC 2.7.11.1) | None |
| O60341 | KDM1A | T99 | 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}. |
| O60739 | EIF1B | T43 | ochoa | Eukaryotic translation initiation factor 1b (eIF1b) (Protein translation factor SUI1 homolog GC20) | Probably involved in translation. |
| O75052 | NOS1AP | T216 | 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}. |
| O75061 | DNAJC6 | T666 | 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}. |
| O75369 | FLNB | T907 | 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. |
| O75533 | SF3B1 | T203 | 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 | T299 | 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}. |
| O75791 | GRAP2 | T192 | 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. |
| O75791 | GRAP2 | T262 | ochoa|psp | 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. |
| O76021 | RSL1D1 | T464 | ochoa | Ribosomal L1 domain-containing protein 1 (CATX-11) (Cellular senescence-inhibited gene protein) (Protein PBK1) | Regulates cellular senescence through inhibition of PTEN translation. Acts as a pro-apoptotic regulator in response to DNA damage. {ECO:0000269|PubMed:18678645, ECO:0000269|PubMed:22419112}. |
| O76041 | NEBL | T813 | ochoa | Nebulette (Actin-binding Z-disk protein) | Binds to actin and plays an important role in the assembly of the Z-disk. May functionally link sarcomeric actin to the desmin intermediate filaments in the heart muscle sarcomeres (PubMed:27733623). {ECO:0000269|PubMed:27733623}.; FUNCTION: [Isoform 2]: May play a role in the assembly of focal adhesions. {ECO:0000269|PubMed:15004028}. |
| O94851 | MICAL2 | T282 | ochoa | [F-actin]-monooxygenase MICAL2 (EC 1.14.13.225) (MICAL C-terminal-like protein) (Mical-cL) (Molecule interacting with CasL protein 2) (MICAL-2) | Methionine monooxygenase that promotes depolymerization of F-actin by mediating oxidation of residues 'Met-44' and 'Met-47' on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (PubMed:24440334, PubMed:29343822). Regulates the disassembly of branched actin networks also by oxidizing ARP3B-containing ARP2/3 complexes leading to ARP3B dissociation from the network (PubMed:34106209). Acts as a key regulator of the SRF signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A through RhoA (PubMed:24440334). {ECO:0000269|PubMed:24440334, ECO:0000269|PubMed:29343822, ECO:0000269|PubMed:34106209}. |
| O95104 | SCAF4 | T138 | ochoa | SR-related and CTD-associated factor 4 (CTD-binding SR-like protein RA4) (Splicing factor, arginine/serine-rich 15) | Anti-terminator protein required to prevent early mRNA termination during transcription (PubMed:31104839). Together with SCAF8, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins (PubMed:31104839). Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation (PubMed:31104839). Independently of SCAF8, also acts as a suppressor of transcriptional readthrough (PubMed:31104839). {ECO:0000269|PubMed:31104839}. |
| O95235 | KIF20A | T686 | 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}. |
| O95359 | TACC2 | T2238 | 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}. |
| O95613 | PCNT | T2154 | 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}. |
| O95866 | MPIG6B | T127 | ochoa | Megakaryocyte and platelet inhibitory receptor G6b (Protein G6b) | Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (PubMed:12665801, PubMed:17311996, PubMed:27743390). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide (PubMed:12665801). This regulation of megakaryocate function as well as platelet production ann activation is done through the inhibition (via the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling (PubMed:17311996). Appears to operate in a calcium-independent manner (PubMed:12665801). {ECO:0000269|PubMed:12665801, ECO:0000269|PubMed:17311996, ECO:0000269|PubMed:27743390}.; FUNCTION: Isoform B, displayed in this entry, is the only isoform to contain both a transmembrane region and 2 immunoreceptor tyrosine-based inhibitor motifs (ITIMs) and, thus, the only one which probably has a role of inhibitory receptor. Isoform A may be the activating counterpart of isoform B. {ECO:0000305|PubMed:11544253}. |
| P00441 | SOD1 | T55 | ochoa | Superoxide dismutase [Cu-Zn] (EC 1.15.1.1) (Superoxide dismutase 1) (hSod1) | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}. |
| P00441 | SOD1 | T89 | ochoa | Superoxide dismutase [Cu-Zn] (EC 1.15.1.1) (Superoxide dismutase 1) (hSod1) | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}. |
| P00568 | AK1 | T35 | ochoa | Adenylate kinase isoenzyme 1 (AK 1) (EC 2.7.4.3) (EC 2.7.4.4) (EC 2.7.4.6) (ATP-AMP transphosphorylase 1) (ATP:AMP phosphotransferase) (Adenylate monophosphate kinase) (Myokinase) | Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism (By similarity) (PubMed:21080915, PubMed:23416111, PubMed:2542324). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (By similarity). {ECO:0000250|UniProtKB:P05081, ECO:0000255|HAMAP-Rule:MF_03171, ECO:0000269|PubMed:21080915, ECO:0000269|PubMed:23416111, ECO:0000269|PubMed:2542324}. |
| P02671 | FGA | T525 | 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}. |
| P04075 | ALDOA | T123 | 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}. |
| P04350 | TUBB4A | T55 | 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. |
| P06127 | CD5 | T436 | psp | T-cell surface glycoprotein CD5 (Lymphocyte antigen T1/Leu-1) (CD antigen CD5) | Lymphoid-specific receptor expressed by all T-cells and in a subset of B-cells known as B1a cells. Plays a role in the regulation of TCR and BCR signaling, thymocyte selection, T-cell effector differentiation and immune tolerance. Acts by interacting with several ligands expressed on B-cells such as CD5L or CD72 and thereby plays an important role in contact-mediated, T-dependent B-cell activation and in the maintenance of regulatory T and B-cell homeostasis. Functions as a negative regulator of TCR signaling during thymocyte development by associating with several signaling proteins including LCK, CD3Z chain, PI3K or CBL (PubMed:1384049, PubMed:1385158). Mechanistically, co-engagement of CD3 with CD5 enhances phosphorylated CBL recruitment leading to increased VAV1 phosphorylation and degradation (PubMed:23376399). Modulates B-cell biology through ERK1/2 activation in a Ca(2+)-dependent pathway via the non-selective Ca(2+) channel TRPC1, leading to IL-10 production (PubMed:27499044). {ECO:0000250|UniProtKB:P13379, ECO:0000269|PubMed:1384049, ECO:0000269|PubMed:1385158, ECO:0000269|PubMed:23376399, ECO:0000269|PubMed:27499044}. |
| P07437 | TUBB | T55 | 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. |
| P07900 | HSP90AA1 | T90 | psp | 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}. |
| P08047 | SP1 | T739 | 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}. |
| P08172 | CHRM2 | T271 | psp | Muscarinic acetylcholine receptor M2 | 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 adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol. {ECO:0000269|PubMed:24256733, ECO:0000269|PubMed:3443095}. |
| P09874 | PARP1 | T109 | ochoa | Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] | Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). 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). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}. |
| P0CG40 | SP9 | T30 | ochoa | Transcription factor Sp9 | Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos (By similarity). {ECO:0000250}. |
| P0DPH7 | TUBA3C | T51 | 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. |
| P0DPH7 | TUBA3C | T381 | 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. |
| P0DPH7 | TUBA3C | T382 | 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 | T51 | 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. |
| P0DPH8 | TUBA3D | T381 | 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. |
| P0DPH8 | TUBA3D | T382 | 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. |
| P10768 | ESD | T83 | 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}. |
| P11388 | TOP2A | T1403 | ochoa | 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}. |
| P11831 | SRF | T159 | psp | Serum response factor (SRF) | SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. 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. Required for cardiac differentiation and maturation. {ECO:0000250|UniProtKB:Q9JM73}. |
| P13611 | VCAN | T563 | 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. |
| P14923 | JUP | T58 | ochoa | Junction plakoglobin (Catenin gamma) (Desmoplakin III) (Desmoplakin-3) | Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). {ECO:0000250}. |
| P15036 | ETS2 | T22 | ochoa | Protein C-ets-2 | Transcription factor activating transcription. Binds specifically the DNA GGAA/T core motif (Ets-binding site or EBS) in gene promoters and stimulates transcription. {ECO:0000269|PubMed:11909962}. |
| P15336 | ATF2 | T73 | ochoa|psp | Cyclic AMP-dependent transcription factor ATF-2 (cAMP-dependent transcription factor ATF-2) (Activating transcription factor 2) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (HB16) (cAMP response element-binding protein CRE-BP1) | Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro (PubMed:10821277). In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. {ECO:0000269|PubMed:10821277, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:22304920}. |
| P16066 | NPR1 | T545 | 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 | T1702 | 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}. |
| P16615 | ATP2A2 | T532 | 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}. |
| P17612 | PRKACA | T196 | 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}. |
| P17812 | CTPS1 | T25 | ochoa | CTP synthase 1 (EC 6.3.4.2) (CTP synthetase 1) (UTP--ammonia ligase 1) | This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity. {ECO:0000269|PubMed:16179339, ECO:0000269|PubMed:24870241}. |
| P18887 | XRCC1 | T523 | 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}. |
| P19338 | NCL | T367 | ochoa | 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}. |
| P20290 | BTF3 | T82 | 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}. |
| P20963 | CD247 | T147 | ochoa | T-cell surface glycoprotein CD3 zeta chain (T-cell receptor T3 zeta chain) (CD antigen CD247) | Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:1384049, PubMed:1385158, PubMed:2470098, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity). {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:1384049, ECO:0000269|PubMed:1385158, ECO:0000269|PubMed:16027224, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7509083}. |
| P21291 | CSRP1 | T102 | ochoa | Cysteine and glycine-rich protein 1 (Cysteine-rich protein 1) (CRP) (CRP1) (Epididymis luminal protein 141) (HEL-141) | Could play a role in neuronal development. |
| P21333 | FLNA | T1286 | 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 | T1369 | 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 | T165 | 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}. |
| P22612 | PRKACG | T196 | ochoa | 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. |
| P22694 | PRKACB | T196 | 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}. |
| P23142 | FBLN1 | T150 | ochoa | Fibulin-1 (FIBL-1) | Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes. Has been implicated in a role in cellular transformation and tumor invasion, it appears to be a tumor suppressor. May play a role in haemostasis and thrombosis owing to its ability to bind fibrinogen and incorporate into clots. Could play a significant role in modulating the neurotrophic activities of APP, particularly soluble APP. {ECO:0000269|PubMed:11792823, ECO:0000269|PubMed:9393974, ECO:0000269|PubMed:9466671}. |
| P27448 | MARK3 | T440 | ochoa | MAP/microtubule affinity-regulating kinase 3 (EC 2.7.11.1) (C-TAK1) (cTAK1) (Cdc25C-associated protein kinase 1) (ELKL motif kinase 2) (EMK-2) (Protein kinase STK10) (Ser/Thr protein kinase PAR-1) (Par-1a) (Serine/threonine-protein kinase p78) | Serine/threonine-protein kinase (PubMed:16822840, PubMed:16980613, PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216' (PubMed:12941695). 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 (PubMed:16980613). Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol (PubMed:16822840). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). Phosphorylates PKP2 and KSR1 (PubMed:12941695). {ECO:0000269|PubMed:12941695, ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}. |
| P27816 | MAP4 | T631 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P29401 | TKT | T346 | ochoa | 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}. |
| P30305 | CDC25B | T127 | 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}. |
| P30626 | SRI | T150 | psp | Sorcin (22 kDa protein) (CP-22) (CP22) (V19) | Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the heart sarcoplasmic reticulum. Modulates the activity of RYR2 calcium channels. {ECO:0000269|PubMed:17699613}. |
| P31146 | CORO1A | T412 | psp | Coronin-1A (Coronin-like protein A) (Clipin-A) (Coronin-like protein p57) (Tryptophan aspartate-containing coat protein) (TACO) | May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes. {ECO:0000269|PubMed:10338208}. |
| P31415 | CASQ1 | T124 | ochoa | Calsequestrin-1 (Calmitine) (Calsequestrin, skeletal muscle isoform) | Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle (PubMed:28895244). Calcium ions are bound by clusters of acidic residues at the protein surface, often at the interface between subunits. Can bind around 80 Ca(2+) ions (PubMed:28895244). Regulates the release of lumenal Ca(2+) via the calcium release channel RYR1; this plays an important role in triggering muscle contraction. Negatively regulates store-operated Ca(2+) entry (SOCE) activity (PubMed:27185316). {ECO:0000269|PubMed:22337878, ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244, ECO:0000303|PubMed:22337878}. |
| P33981 | TTK | T675 | 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}. |
| P35222 | CTNNB1 | T384 | psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35408 | PTGER4 | T428 | ochoa | 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. |
| P35611 | ADD1 | T445 | psp | Alpha-adducin (Erythrocyte adducin subunit alpha) | Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin. |
| P35611 | ADD1 | T480 | ochoa|psp | Alpha-adducin (Erythrocyte adducin subunit alpha) | Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin. |
| P35637 | FUS | T68 | psp | RNA-binding protein FUS (75 kDa DNA-pairing protein) (Oncogene FUS) (Oncogene TLS) (POMp75) (Translocated in liposarcoma protein) | DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Also binds its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). {ECO:0000250|UniProtKB:P56959, ECO:0000269|PubMed:10567410, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:24204307, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27731383}. |
| P35869 | AHR | T361 | ochoa | Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) | Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. |
| P35869 | AHR | T697 | psp | Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) | Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. |
| P38936 | CDKN1A | T57 | 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}. |
| P39210 | MPV17 | T80 | psp | Mitochondrial inner membrane protein Mpv17 (Protein Mpv17) | Non-selective channel that modulates the membrane potential under normal conditions and oxidative stress, and is involved in mitochondrial homeostasis (PubMed:25861990). Involved in mitochondrial deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial DNA (mtDNA) maintenance (PubMed:26760297). May be involved in the regulation of reactive oxygen species metabolism and the control of oxidative phosphorylation (By similarity). {ECO:0000250|UniProtKB:P19258, ECO:0000269|PubMed:25861990, ECO:0000269|PubMed:26760297}. |
| P40121 | CAPG | T130 | ochoa | Macrophage-capping protein (Actin regulatory protein CAP-G) | Calcium-sensitive protein which reversibly blocks the barbed ends of actin filaments but does not sever preformed actin filaments. May play an important role in macrophage function. May play a role in regulating cytoplasmic and/or nuclear structures through potential interactions with actin. May bind DNA. |
| P40189 | IL6ST | T783 | 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}. |
| P40926 | MDH2 | T54 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P41567 | EIF1 | T43 | ochoa | Eukaryotic translation initiation factor 1 (eIF1) (A121) (Protein translation factor SUI1 homolog) (Sui1iso1) | Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon (PubMed:12435632, PubMed:14600024, PubMed:9732867). Together with eIF1A (EIF1AX), EIF1 facilitates scanning and is essential for start codon recognition on the basis of AUG nucleotide context and location relative to the 5'-cap (PubMed:12435632, PubMed:14600024, PubMed:9732867). Participates to initiation codon selection by influencing the conformation of the 40S ribosomal subunit and the positions of bound mRNA and initiator tRNA; this is possible after its binding to the interface surface of the platform of the 40S ribosomal subunit close to the P-site (PubMed:14600024). Together with eIF1A (EIF1AX), also regulates the opening and closing of the mRNA binding channel, which ensures mRNA recruitment, scanning and the fidelity of initiation codon selection (PubMed:9732867). Continuously monitors and protects against premature and partial base-pairing of codons in the 5'-UTR with the anticodon of initiator tRNA (PubMed:12435632, PubMed:9732867). Together with eIF1A (EIF1AX), acts for ribosomal scanning, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes (PubMed:9732867). Interacts with EIF4G1, which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site (PubMed:29987188). EIF4G1-EIF1 complex promotes ribosome scanning (on both short and long 5'UTR), leaky scanning (on short 5'UTR) which is the bypass of the initial start codon, and discrimination against cap-proximal AUG (PubMed:29987188). Is probably maintained within the 43S PIC in open conformation thanks to eIF1A-EIF5 interaction (PubMed:24319994). Once the correct start codon is reached, EIF1 is physically excluded from the decoding site, shifting the PIC into the closed conformation and arresting it at the start codon (PubMed:22813744). {ECO:0000269|PubMed:12435632, ECO:0000269|PubMed:14600024, ECO:0000269|PubMed:22813744, ECO:0000269|PubMed:29987188, ECO:0000269|PubMed:9732867}. |
| P42261 | GRIA1 | T858 | psp | Glutamate receptor 1 (GluR-1) (AMPA-selective glutamate receptor 1) (GluR-A) (GluR-K1) (Glutamate receptor ionotropic, AMPA 1) | Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex (PubMed:21172611). Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity). {ECO:0000250|UniProtKB:P19490, ECO:0000269|PubMed:1311100, ECO:0000269|PubMed:20805473, ECO:0000269|PubMed:21172611, ECO:0000269|PubMed:28628100, ECO:0000269|PubMed:35675825}. |
| P45379 | TNNT2 | T213 | psp | Troponin T, cardiac muscle (TnTc) (Cardiac muscle troponin T) (cTnT) | Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. |
| P45880 | VDAC2 | T66 | ochoa | Non-selective voltage-gated ion channel VDAC2 (VDAC-2) (hVDAC2) (Outer mitochondrial membrane protein porin 2) | Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:8420959). The channel adopts an open conformation at zero mV and a closed conformation at both positive and negative potentials (PubMed:8420959). There are two populations of channels; the main that functions in a lower open-state conductance with lower ion selectivity, that switch, in a voltage-dependent manner, from the open to a low-conducting 'closed' state and the other that has a normal ion selectivity in the typical high conductance, 'open' state (PubMed:8420959). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:31015432). Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (PubMed:31015432). {ECO:0000269|PubMed:31015432, 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}. |
| P48048 | KCNJ1 | T193 | psp | ATP-sensitive inward rectifier potassium channel 1 (ATP-regulated potassium channel ROM-K) (Inward rectifier K(+) channel Kir1.1) (Potassium channel, inwardly rectifying subfamily J member 1) | Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium. In the kidney, probably plays a major role in potassium homeostasis. {ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:7929082}. |
| P49321 | NASP | T404 | 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}. |
| P49418 | AMPH | T387 | psp | Amphiphysin | May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton. |
| P49419 | ALDH7A1 | T521 | ochoa | Alpha-aminoadipic semialdehyde dehydrogenase (Alpha-AASA dehydrogenase) (EC 1.2.1.31) (Aldehyde dehydrogenase family 7 member A1) (EC 1.2.1.3) (Antiquitin-1) (Betaine aldehyde dehydrogenase) (EC 1.2.1.8) (Delta1-piperideine-6-carboxylate dehydrogenase) (P6c dehydrogenase) | Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:20207735, ECO:0000269|PubMed:21338592}. |
| P50552 | VASP | T278 | psp | Vasodilator-stimulated phosphoprotein (VASP) | Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation. {ECO:0000269|PubMed:10087267, ECO:0000269|PubMed:10438535, ECO:0000269|PubMed:15939738, ECO:0000269|PubMed:17082196, ECO:0000269|PubMed:18559661}. |
| P50851 | LRBA | T1782 | 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}. |
| P51788 | CLCN2 | T706 | ochoa | Chloride channel protein 2 (ClC-2) | Voltage-gated and osmosensitive chloride channel. Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Displays inward rectification currents activated upon membrane hyperpolarization and extracellular hypotonicity (PubMed:16155254, PubMed:17567819, PubMed:19191339, PubMed:23632988, PubMed:29403011, PubMed:29403012, PubMed:36964785, PubMed:38345841). Contributes to chloride conductance involved in neuron excitability. In hippocampal neurons, generates a significant part of resting membrane conductance and provides an additional chloride efflux pathway to prevent chloride accumulation in dendrites upon GABA receptor activation. In glia, associates with the auxiliary subunit HEPACAM/GlialCAM at astrocytic processes and myelinated fiber tracts where it may regulate transcellular chloride flux buffering extracellular chloride and potassium concentrations (PubMed:19191339, PubMed:22405205, PubMed:23707145). Regulates aldosterone production in adrenal glands. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated calcium channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (PubMed:29403011, PubMed:29403012). Contributes to chloride conductance in retinal pigment epithelium involved in phagocytosis of shed photoreceptor outer segments and photoreceptor renewal (PubMed:36964785). Conducts chloride currents at the basolateral membrane of epithelial cells with a role in chloride reabsorption rather than secretion (By similarity) (PubMed:16155254). Permeable to small monovalent anions with chloride > thiocyanate > bromide > nitrate > iodide ion selectivity (By similarity) (PubMed:29403012). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:Q9R0A1, ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:19191339, ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:23632988, ECO:0000269|PubMed:23707145, ECO:0000269|PubMed:29403011, ECO:0000269|PubMed:29403012, ECO:0000269|PubMed:36964785, ECO:0000269|PubMed:38345841}. |
| P51817 | PRKX | T201 | ochoa | cAMP-dependent protein kinase catalytic subunit PRKX (PrKX) (Protein kinase X) (Protein kinase X-linked) (Serine/threonine-protein kinase PRKX) (EC 2.7.11.1) (Protein kinase PKX1) | Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation. {ECO:0000269|PubMed:12082174, ECO:0000269|PubMed:16236808, ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:17980165, ECO:0000269|PubMed:19367327, ECO:0000269|PubMed:21684272, ECO:0000269|PubMed:9860982}. |
| P55011 | SLC12A2 | T207 | psp | 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}. |
| P55084 | HADHB | T85 | ochoa | Trifunctional enzyme subunit beta, mitochondrial (TP-beta) [Includes: 3-ketoacyl-CoA thiolase (EC 2.3.1.155) (EC 2.3.1.16) (Acetyl-CoA acyltransferase) (Beta-ketothiolase)] | Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:29915090, PubMed:30850536, PubMed:8135828). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity (PubMed:29915090, PubMed:30850536, PubMed:8135828). {ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}. |
| P55265 | ADAR | T811 | ochoa | Double-stranded RNA-specific adenosine deaminase (DRADA) (EC 3.5.4.37) (136 kDa double-stranded RNA-binding protein) (p136) (Interferon-inducible protein 4) (IFI-4) (K88DSRBP) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). 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 since the translational machinery read the inosine as a guanosine; 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 serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}. |
| P55786 | NPEPPS | T136 | 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}. |
| P56192 | MARS1 | T835 | ochoa | 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}. |
| P57059 | SIK1 | T577 | ochoa | 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}. |
| P60763 | RAC3 | T167 | ochoa | Ras-related C3 botulinum toxin substrate 3 (EC 3.6.5.2) (p21-Rac3) | Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles. Promotes cell adhesion and spreading on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner. {ECO:0000269|PubMed:11756406, ECO:0000269|PubMed:11956649}. |
| P61353 | RPL27 | T33 | ochoa | Large ribosomal subunit protein eL27 (60S ribosomal protein L27) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs (PubMed:25424902). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25424902, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P62913 | RPL11 | T47 | ochoa|psp | 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}. |
| P63000 | RAC1 | T167 | ochoa | Ras-related C3 botulinum toxin substrate 1 (EC 3.6.5.2) (Cell migration-inducing gene 5 protein) (Ras-like protein TC25) (p21-Rac1) | Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles (PubMed:1643658, PubMed:22843693, PubMed:23512198, PubMed:28886345). Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity (PubMed:9121475). In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (PubMed:1643658). In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity). In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity). Required for DSG3 translocation to cell-cell junctions, DSG3-mediated organization of cortical F-actin bundles and anchoring of actin at cell junctions; via interaction with DSG3 (PubMed:22796473). Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:38355798). {ECO:0000250|UniProtKB:P63001, ECO:0000250|UniProtKB:Q6RUV5, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:22796473, ECO:0000269|PubMed:22843693, ECO:0000269|PubMed:23512198, ECO:0000269|PubMed:28886345, ECO:0000269|PubMed:38355798, ECO:0000269|PubMed:9121475}.; FUNCTION: [Isoform B]: Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins (PubMed:14625275). It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction (PubMed:14625275). {ECO:0000269|PubMed:14625275}. |
| P68363 | TUBA1B | T51 | 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}. |
| P68363 | TUBA1B | T381 | 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}. |
| P68363 | TUBA1B | T382 | 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 | T381 | 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. |
| P68366 | TUBA4A | T382 | 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. |
| P68371 | TUBB4B | T55 | 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. |
| P83436 | COG7 | T437 | ochoa | Conserved oligomeric Golgi complex subunit 7 (COG complex subunit 7) (Component of oligomeric Golgi complex 7) | Required for normal Golgi function. {ECO:0000269|PubMed:11980916}. |
| P98172 | EFNB1 | T308 | 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}. |
| Q01130 | SRSF2 | T29 | ochoa | Serine/arginine-rich splicing factor 2 (Protein PR264) (Splicing component, 35 kDa) (Splicing factor SC35) (SC-35) (Splicing factor, arginine/serine-rich 2) | Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA. 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. Binds to purine-rich RNA sequences, either 5'-AGSAGAGTA-3' (S=C or G) or 5'-GTTCGAGTA-3'. Can bind to beta-globin mRNA and commit it to the splicing pathway. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment. {ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21157427}. |
| Q02952 | AKAP12 | T725 | 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). |
| Q03393 | PTS | T58 | psp | 6-pyruvoyl tetrahydrobiopterin synthase (PTP synthase) (PTPS) (EC 4.2.3.12) | Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin. {ECO:0000269|PubMed:1282802}. |
| Q04637 | EIF4G1 | T1054 | 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}. |
| Q06710 | PAX8 | T277 | psp | Paired box protein Pax-8 | Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells. |
| Q07955 | SRSF1 | T29 | ochoa | 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 | T882 | 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 | T346 | 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}. |
| Q08379 | GOLGA2 | T70 | 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}. |
| Q08AD1 | CAMSAP2 | T426 | 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}. |
| Q08J23 | NSUN2 | T725 | ochoa | RNA cytosine C(5)-methyltransferase NSUN2 (EC 2.1.1.-) (Myc-induced SUN domain-containing protein) (Misu) (NOL1/NOP2/Sun domain family member 2) (Substrate of AIM1/Aurora kinase B) (mRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (tRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-, EC 2.1.1.203) (tRNA methyltransferase 4 homolog) (hTrm4) | RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847). {ECO:0000250|UniProtKB:Q1HFZ0, ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:22995836, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31199786, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:34556860}. |
| Q09666 | AHNAK | T161 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T694 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T4877 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q10571 | MN1 | T957 | ochoa | Transcriptional activator MN1 (Probable tumor suppressor protein MN1) | Transcriptional activator which specifically regulates expression of TBX22 in the posterior region of the developing palate. Required during later stages of palate development for growth and medial fusion of the palatal shelves. Promotes maturation and normal function of calvarial osteoblasts, including expression of the osteoclastogenic cytokine TNFSF11/RANKL. Necessary for normal development of the membranous bones of the skull (By similarity). May play a role in tumor suppression (Probable). {ECO:0000250|UniProtKB:D3YWE6, ECO:0000305|PubMed:7731706}. |
| Q12888 | TP53BP1 | T1198 | 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 | T1709 | 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}. |
| Q13164 | MAPK7 | T219 | ochoa|psp | Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) | Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}. |
| Q13177 | PAK2 | T178 | 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}. |
| Q13228 | SELENBP1 | T284 | 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}. |
| Q13286 | CLN3 | T19 | ochoa | Battenin (Batten disease protein) (Protein CLN3) | Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocytosis, autophagy, transport of proteins and lipids from the TGN, apoptosis and synaptic transmission (PubMed:10924275, PubMed:15471887, PubMed:18317235, PubMed:18817525, PubMed:20850431, PubMed:22261744). Facilitates the proteins transport from trans-Golgi network (TGN)-to other membrane compartments such as transport of microdomain-associated proteins to the plasma membrane, IGF2R transport to the lysosome where it regulates the CTSD release leading to regulation of CTSD maturation and thereby APP intracellular processing (PubMed:10924275, PubMed:18817525). Moreover regulates CTSD activity in response to osmotic stress (PubMed:23840424, PubMed:28390177). Also binds galactosylceramide and transports it from the trans Golgi to the rafts, which may have immediate and downstream effects on cell survival by modulating ceramide synthesis (PubMed:18317235). At the plasma membrane, regulates actin-dependent events including filopodia formation, cell migration, and pinocytosis through ARF1-CDC42 pathway and also the cytoskeleton organization through interaction with MYH10 and fodrin leading to the regulation of the plasma membrane association of Na+, K+ ATPase complex (PubMed:20850431). Regulates synaptic transmission in the amygdala, hippocampus, and cerebellum through regulation of synaptic vesicles density and their proximity to active zones leading to modulation of short-term plasticity and age-dependent anxious behavior, learning and memory (By similarity). Regulates autophagic vacuoles (AVs) maturation by modulating the trafficking between endocytic and autophagolysosomal/lysosomal compartments, which involves vesicle fusion leading to regulation of degradation process (By similarity). Also participates in cellular homeostasis of compounds such as, water, ions, amino acids, proteins and lipids in several tissue namely in brain and kidney through regulation of their transport and synthesis (PubMed:17482562). {ECO:0000250|UniProtKB:Q61124, ECO:0000269|PubMed:10924275, ECO:0000269|PubMed:15471887, ECO:0000269|PubMed:17482562, ECO:0000269|PubMed:18317235, ECO:0000269|PubMed:18817525, ECO:0000269|PubMed:20850431, ECO:0000269|PubMed:22261744, ECO:0000269|PubMed:23840424, ECO:0000269|PubMed:28390177}. |
| Q13418 | ILK | T173 | psp | Scaffold protein ILK (ILK-1) (ILK-2) (Inactive integrin-linked kinase) (p59ILK) | Scaffold protein which mediates protein-protein interactions during a range of cellular events including focal adhesion assembly, cell adhesion and cell migration (PubMed:17420447, PubMed:20005845, PubMed:30367047, PubMed:32528174). Regulates integrin-mediated signal transduction by contributing to inside-out integrin activation (By similarity). Recruits PARVA and LIMS1/PITCH to form the heterotrimeric IPP (ILK-PINCH-PARVIN) complex which binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration (PubMed:30367047). Binding to PARVA promotes effective assembly of ILK into focal adhesions while PARVA-bound ILK can simultaneously engage integrin-beta cytoplasmic tails to mediate cell adhesion (PubMed:20005845). Plays a role with PARVG in promoting the cell adhesion and spreading of leukocytes (PubMed:16517730). Acts as an upstream effector of both AKT1/PKB and GSK3 (PubMed:9736715). Mediates trafficking of caveolae to the cell surface in an ITGB1-dependent manner by promoting the recruitment of IQGAP1 to the cell cortex which cooperates with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Required for the maintenance of mitotic spindle integrity by promoting phosphorylation of TACC3 by AURKA (PubMed:18283114). Associates with chromatin and may act as a negative regulator of transcription when located in the nucleus (PubMed:17420447). {ECO:0000250|UniProtKB:O55222, ECO:0000250|UniProtKB:Q99J82, ECO:0000269|PubMed:16517730, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:18283114, ECO:0000269|PubMed:20005845, ECO:0000269|PubMed:30367047, ECO:0000269|PubMed:32528174, ECO:0000269|PubMed:9736715}. |
| Q13428 | TCOF1 | T1222 | 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 | T1260 | 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 | T1385 | 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}. |
| Q13485 | SMAD4 | T269 | psp | Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (Deletion target in pancreatic carcinoma 4) (SMAD family member 4) (SMAD 4) (Smad4) (hSMAD4) | In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. {ECO:0000250, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:9389648}. |
| Q13492 | PICALM | T573 | 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 | T350 | ochoa|psp | 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}. |
| Q13561 | DCTN2 | T206 | ochoa | Dynactin subunit 2 (50 kDa dynein-associated polypeptide) (Dynactin complex 50 kDa subunit) (DCTN-50) (p50 dynamitin) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (By similarity). {ECO:0000250|UniProtKB:A0A5G2QD80, ECO:0000250|UniProtKB:Q99KJ8}. |
| Q13643 | FHL3 | T189 | ochoa | Four and a half LIM domains protein 3 (FHL-3) (Skeletal muscle LIM-protein 2) (SLIM-2) | Recruited by SOX15 to FOXK1 promoters where it acts as a transcriptional coactivator of FOXK1. {ECO:0000250|UniProtKB:Q9R059}. |
| Q14161 | GIT2 | T195 | 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}. |
| Q14247 | CTTN | T24 | 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 | T423 | 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}. |
| Q14324 | MYBPC2 | T118 | ochoa | Myosin-binding protein C, fast-type (Fast MyBP-C) (C-protein, skeletal muscle fast isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. |
| Q14324 | MYBPC2 | T830 | ochoa | Myosin-binding protein C, fast-type (Fast MyBP-C) (C-protein, skeletal muscle fast isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. |
| Q14498 | RBM39 | T330 | ochoa | RNA-binding protein 39 (CAPER alpha) (CAPERalpha) (Hepatocellular carcinoma protein 1) (RNA-binding motif protein 39) (RNA-binding region-containing protein 2) (Splicing factor HCC1) | RNA-binding protein that acts as a pre-mRNA splicing factor (PubMed:15694343, PubMed:24795046, PubMed:28302793, PubMed:28437394, PubMed:31271494). Acts by promoting exon inclusion via regulation of exon cassette splicing (PubMed:31271494). Also acts as a transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1, independently of the pre-mRNA splicing factor activity (By similarity). {ECO:0000250|UniProtKB:Q8VH51, ECO:0000269|PubMed:15694343, ECO:0000269|PubMed:24795046, ECO:0000269|PubMed:28302793, ECO:0000269|PubMed:28437394, ECO:0000269|PubMed:31271494}. |
| Q14644 | RASA3 | T110 | 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. |
| Q14667 | BLTP2 | T1485 | ochoa | Bridge-like lipid transfer protein family member 2 (Antigen MLAA-22) (Breast cancer-overexpressed gene 1 protein) (Protein hobbit homolog) | Tube-forming lipid transport protein which binds to phosphatidylinositols and affects phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) distribution. {ECO:0000250|UniProtKB:Q9VZS7}. |
| Q14669 | TRIP12 | T969 | 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}. |
| Q14689 | DIP2A | T279 | 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}. |
| Q14847 | LASP1 | T63 | 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}. |
| Q14872 | MTF1 | T252 | psp | Metal regulatory transcription factor 1 (MRE-binding transcription factor) (Transcription factor MTF-1) | Zinc-dependent transcriptional regulator of cellular adaption to conditions of exposure to heavy metals (PubMed:8065932). Binds to metal responsive elements (MRE) in promoters and activates the transcription of metallothionein genes like metallothionein-2/MT2A (PubMed:8065932). Also regulates the expression of metalloproteases in response to intracellular zinc and functions as a catabolic regulator of cartilages (By similarity). {ECO:0000250|UniProtKB:Q07243, ECO:0000269|PubMed:8065932}. |
| Q14934 | NFATC4 | T330 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 4 (NF-ATc4) (NFATc4) (T-cell transcription factor NFAT3) (NF-AT3) | Ca(2+)-regulated transcription factor that is involved in several processes, including the development and function of the immune, cardiovascular, musculoskeletal, and nervous systems (PubMed:11514544, PubMed:11997522, PubMed:17213202, PubMed:17875713, PubMed:18668201, PubMed:25663301, PubMed:7749981). Involved in T-cell activation, stimulating the transcription of cytokine genes, including that of IL2 and IL4 (PubMed:18347059, PubMed:18668201, PubMed:7749981). Along with NFATC3, involved in embryonic heart development. Following JAK/STAT signaling activation and as part of a complex with NFATC3 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). Involved in mitochondrial energy metabolism required for cardiac morphogenesis and function (By similarity). Transactivates many genes involved in the cardiovascular system, including AGTR2, NPPB/BNP (in synergy with GATA4), NPPA/ANP/ANF and MYH7/beta-MHC (By similarity). Involved in the regulation of adult hippocampal neurogenesis. Involved in BDNF-driven pro-survival signaling in hippocampal adult-born neurons. Involved in the formation of long-term spatial memory and long-term potentiation (By similarity). In cochlear nucleus neurons, may play a role in deafferentation-induced apoptosis during the developmental critical period, when auditory neurons depend on afferent input for survival (By similarity). Binds to and activates the BACE1/Beta-secretase 1 promoter, hence may regulate the proteolytic processing of the amyloid precursor protein (APP) (PubMed:25663301). Plays a role in adipocyte differentiation (PubMed:11997522). May be involved in myoblast differentiation into myotubes (PubMed:17213202). Binds the consensus DNA sequence 5'-GGAAAAT-3' (Probable). In the presence of CREBBP, activates TNF transcription (PubMed:11514544). Binds to PPARG gene promoter and regulates its activity (PubMed:11997522). Binds to PPARG and REG3G gene promoters (By similarity). {ECO:0000250|UniProtKB:D3Z9H7, ECO:0000250|UniProtKB:Q8K120, ECO:0000269|PubMed:11514544, ECO:0000269|PubMed:11997522, ECO:0000269|PubMed:17213202, ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:18347059, ECO:0000269|PubMed:18668201, ECO:0000269|PubMed:25663301, ECO:0000269|PubMed:7749981, ECO:0000305}. |
| Q15003 | NCAPH | T598 | 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}. |
| Q15032 | R3HDM1 | T974 | ochoa | R3H domain-containing protein 1 | None |
| Q15056 | EIF4H | T43 | 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}. |
| Q15118 | PDK1 | T338 | psp | [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}. |
| Q15149 | PLEC | T3277 | 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}. |
| Q15233 | NONO | T432 | 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}. |
| Q15392 | DHCR24 | T110 | psp | Delta(24)-sterol reductase (EC 1.3.1.72) (24-dehydrocholesterol reductase) (3-beta-hydroxysterol Delta-24-reductase) (Diminuto/dwarf1 homolog) (Seladin-1) | Catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis (PubMed:11519011, PubMed:21671375, PubMed:22178193, PubMed:25637936). In addition to its cholesterol-synthesizing activity, can protect cells from oxidative stress by reducing caspase 3 activity during apoptosis induced by oxidative stress (PubMed:11007892, PubMed:22010141). Also protects against amyloid-beta peptide-induced apoptosis (PubMed:11007892). {ECO:0000269|PubMed:11007892, ECO:0000269|PubMed:11519011, ECO:0000269|PubMed:21671375, ECO:0000269|PubMed:22010141, ECO:0000269|PubMed:22178193, ECO:0000269|PubMed:25637936}. |
| Q15596 | NCOA2 | T729 | 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 | T128 | 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}. |
| Q15599 | NHERF2 | T284 | 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}. |
| Q15831 | STK11 | T363 | psp | Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1) (LKB1) (hLKB1) (Renal carcinoma antigen NY-REN-19) | Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250}. |
| Q16204 | CCDC6 | T60 | ochoa | Coiled-coil domain-containing protein 6 (Papillary thyroid carcinoma-encoded protein) (Protein H4) | None |
| Q16512 | PKN1 | T302 | ochoa | 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}. |
| Q16775 | HAGH | T142 | ochoa | Hydroxyacylglutathione hydrolase, mitochondrial (EC 3.1.2.6) (Glyoxalase II) (Glx II) | Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid. {ECO:0000269|PubMed:8550579}. |
| Q2M2I8 | AAK1 | T694 | 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}. |
| Q32MZ4 | LRRFIP1 | T537 | 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}. |
| Q53HL2 | CDCA8 | T94 | psp | Borealin (Cell division cycle-associated protein 8) (Dasra-B) (hDasra-B) (Pluripotent embryonic stem cell-related gene 3 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. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment. {ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15260989, ECO:0000269|PubMed:16571674, ECO:0000269|PubMed:18243099}. |
| Q58WW2 | DCAF6 | T654 | ochoa | DDB1- and CUL4-associated factor 6 (Androgen receptor complex-associated protein) (ARCAP) (IQ motif and WD repeat-containing protein 1) (Nuclear receptor interaction protein) (NRIP) | Ligand-dependent coactivator of nuclear receptors. Enhance transcriptional activity of the nuclear receptors NR3C1 and AR. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:15784617, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240}. |
| Q5QJE6 | DNTTIP2 | T241 | 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}. |
| Q5T011 | SZT2 | T1196 | ochoa | KICSTOR complex protein SZT2 (Seizure threshold 2 protein homolog) | As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose (PubMed:28199306, PubMed:28199315). May play a role in the cellular response to oxidative stress (By similarity). {ECO:0000250|UniProtKB:A2A9C3, ECO:0000269|PubMed:28199306, ECO:0000269|PubMed:28199315}. |
| Q5T481 | RBM20 | T500 | ochoa | RNA-binding protein 20 (RNA-binding motif protein 20) | RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH (PubMed:22466703, PubMed:24960161, PubMed:26604136, PubMed:27496873, PubMed:27531932, PubMed:29895960, PubMed:30948719, PubMed:32840935, PubMed:34732726, PubMed:35427468). Acts as a repressor of mRNA splicing: specifically binds the 5'UCUU-3' motif that is predominantly found within intronic sequences of pre-mRNAs, leading to the exclusion of specific exons in target transcripts (PubMed:24960161, PubMed:30948719, PubMed:34732726). RBM20-mediated exon skipping is hormone-dependent and is essential for TTN isoform transition in both cardiac and skeletal muscles (PubMed:27531932, PubMed:30948719). RBM20-mediated exon skipping of TTN provides substrates for the formation of circular RNA (circRNAs) from the TTN transcripts (PubMed:27531932, PubMed:34732726). Together with RBM24, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By similarity). {ECO:0000250|UniProtKB:E9PT37, ECO:0000269|PubMed:22466703, ECO:0000269|PubMed:24960161, ECO:0000269|PubMed:26604136, ECO:0000269|PubMed:27496873, ECO:0000269|PubMed:27531932, ECO:0000269|PubMed:29895960, ECO:0000269|PubMed:30948719, ECO:0000269|PubMed:32840935, ECO:0000269|PubMed:34732726, ECO:0000269|PubMed:35427468}. |
| Q5T8R8 | DOCK8-AS1 | T49 | ochoa | Uncharacterized protein DOCK8-AS1 (DOCK8 antisense RNA 1) | None |
| Q5UIP0 | RIF1 | T1712 | 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}. |
| Q5VTT5 | MYOM3 | T1306 | ochoa | Myomesin-3 (Myomesin family member 3) | May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle. {ECO:0000250}. |
| Q5VUJ6 | LRCH2 | T361 | 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}. |
| Q68D20 | PMS2CL | T156 | ochoa | Protein PMS2CL (PMS2-C terminal-like protein) | None |
| Q6JBY9 | RCSD1 | T336 | ochoa | CapZ-interacting protein (Protein kinase substrate CapZIP) (RCSD domain-containing protein 1) | Stress-induced phosphorylation of CAPZIP may regulate the ability of F-actin-capping protein to remodel actin filament assembly. {ECO:0000269|PubMed:15850461}. |
| Q6N022 | TENM4 | T2580 | 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}. |
| Q6PD62 | CTR9 | T925 | ochoa | RNA polymerase-associated protein CTR9 homolog (SH2 domain-binding protein 1) | 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. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3 (By similarity). {ECO:0000250|UniProtKB:Q62018, ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}. |
| Q6PEY2 | TUBA3E | T51 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E 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. |
| Q6R327 | RICTOR | T1592 | 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}. |
| Q6SPF0 | SAMD1 | T401 | 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}. |
| Q6UUV9 | CRTC1 | T75 | 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}. |
| Q6ZRV2 | FAM83H | T433 | 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}. |
| Q71U36 | TUBA1A | T51 | 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. |
| Q71U36 | TUBA1A | T381 | 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. |
| Q71U36 | TUBA1A | T382 | 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 | T854 | 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}. |
| Q7KZI7 | MARK2 | T596 | ochoa|psp | 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}. |
| Q7L8J4 | SH3BP5L | T340 | ochoa | SH3 domain-binding protein 5-like (SH3BP-5-like) | Functions as a guanine nucleotide exchange factor (GEF) for RAB11A. {ECO:0000269|PubMed:30217979}. |
| Q7RTP6 | MICAL3 | T508 | 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}. |
| Q7Z2E3 | APTX | T150 | ochoa | Aprataxin (EC 3.6.1.71) (EC 3.6.1.72) (Forkhead-associated domain histidine triad-like protein) (FHA-HIT) | DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair (PubMed:15044383, PubMed:15380105, PubMed:16964241, PubMed:17276982, PubMed:24362567). Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species (PubMed:16964241, PubMed:24362567). Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined (PubMed:16964241, PubMed:17276982, PubMed:24362567). Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (PubMed:16547001). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity). {ECO:0000250|UniProtKB:O74859, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16547001, ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567}. |
| Q7Z2W4 | ZC3HAV1 | T419 | 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}. |
| Q7Z401 | DENND4A | T897 | 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}. |
| Q7Z434 | MAVS | T465 | 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}. |
| Q7Z6J0 | SH3RF1 | T567 | 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 | T2889 | 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 | T3131 | 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}. |
| Q86U70 | LDB1 | T327 | ochoa | LIM domain-binding protein 1 (LDB-1) (Carboxyl-terminal LIM domain-binding protein 2) (CLIM-2) (LIM domain-binding factor CLIM2) (hLdb1) (Nuclear LIM interactor) | Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state. {ECO:0000250|UniProtKB:P70662}. |
| Q86U86 | PBRM1 | T172 | 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}. |
| Q86YS7 | C2CD5 | T339 | 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}. |
| Q8IVT2 | MISP | T459 | 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}. |
| Q8IWZ3 | ANKHD1 | T86 | 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}. |
| Q8IX01 | SUGP2 | T284 | 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}. |
| Q8IXJ6 | SIRT2 | T101 | psp | 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}. |
| Q8IXS8 | HYCC2 | T489 | ochoa | Hyccin 2 | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. {ECO:0000305|PubMed:26571211}. |
| Q8N108 | MIER1 | T448 | ochoa | Mesoderm induction early response protein 1 (Early response 1) (Er1) (Mi-er1) (hMi-er1) | Transcriptional repressor regulating the expression of a number of genes including SP1 target genes. Probably functions through recruitment of HDAC1 a histone deacetylase involved in chromatin silencing. {ECO:0000269|PubMed:12482978}. |
| Q8N128 | FAM177A1 | T65 | ochoa | Protein FAM177A1 | None |
| Q8N139 | ABCA6 | T1337 | ochoa | ATP-binding cassette sub-family A member 6 (EC 7.6.2.-) | Probable transporter which may play a role in macrophage lipid transport and homeostasis. {ECO:0000305|PubMed:10639163}. |
| Q8N1F7 | NUP93 | T85 | 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}. |
| Q8N4C9 | C17orf78 | T152 | ochoa | Uncharacterized protein C17orf78 | None |
| Q8N8Z6 | DCBLD1 | T572 | ochoa | Discoidin, CUB and LCCL domain-containing protein 1 | None |
| Q8NC51 | SERBP1 | T61 | 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}. |
| Q8NCF5 | NFATC2IP | T342 | ochoa | NFATC2-interacting protein (45 kDa NF-AT-interacting protein) (45 kDa NFAT-interacting protein) (Nuclear factor of activated T-cells, cytoplasmic 2-interacting protein) | In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}. |
| Q8NCN4 | RNF169 | T482 | 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 | T554 | 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}. |
| Q8NEL9 | DDHD1 | T128 | ochoa | Phospholipase DDHD1 (EC 3.1.1.111) (EC 3.1.1.32) (DDHD domain-containing protein 1) (Phosphatidic acid-preferring phospholipase A1 homolog) (PA-PLA1) (EC 3.1.1.118) (Phospholipid sn-1 acylhydrolase) | Phospholipase A1 (PLA1) that hydrolyzes ester bonds at the sn-1 position of glycerophospholipids producing a free fatty acid and a lysophospholipid (Probable) (PubMed:20359546, PubMed:22922100). Prefers phosphatidate (1,2-diacyl-sn-glycero-3-phosphate, PA) as substrate in vitro, but can efficiently hydrolyze phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI), as well as a range of other glycerophospholipid substrates such as phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE), phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) and phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol), PG) (Probable) (PubMed:20359546). Involved in the regulation of the endogenous content of polyunsaturated PI and PS lipids in the nervous system. Changes in these lipids extend to downstream metabolic products like PI phosphates PIP and PIP2, which play fundamental roles in cell biology (By similarity). Regulates mitochondrial morphology (PubMed:24599962). These dynamic changes may be due to PA hydrolysis at the mitochondrial surface (PubMed:24599962). May play a regulatory role in spermatogenesis or sperm function (PubMed:24599962). {ECO:0000250|UniProtKB:Q80YA3, ECO:0000269|PubMed:20359546, ECO:0000269|PubMed:22922100, ECO:0000269|PubMed:24599962, ECO:0000303|PubMed:24599962, ECO:0000305|PubMed:37189713}. |
| Q8NI27 | THOC2 | T1224 | ochoa | THO complex subunit 2 (Tho2) (hTREX120) | Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Required for efficient export of polyadenylated RNA and spliced mRNA (PubMed:23222130). The THOC1-THOC2-THOC3 core complex alone is sufficient to bind export factor NXF1-NXT1 and promote ATPase activity of DDX39B; in the complex THOC2 is the only component that directly interacts with DDX39B (PubMed:33191911). 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). Required for NXF1 localization to the nuclear rim (PubMed:22893130). THOC2 (and probably the THO complex) is involved in releasing mRNA from nuclear speckle domains. {ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:22893130, ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:33191911}.; 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}. |
| Q8TAA3 | PSMA8 | T160 | ochoa | Proteasome subunit alpha-type 8 (Proteasome alpha 4 subunit) (Alpha4s) (Proteasome subunit alpha-type 7-like) | Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. The proteasome is a protein complex that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis. Localizes to the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I. {ECO:0000250|UniProtKB:Q9CWH6}. |
| Q8TAE6 | PPP1R14C | T52 | ochoa | Protein phosphatase 1 regulatory subunit 14C (Kinase-enhanced PP1 inhibitor) (PKC-potentiated PP1 inhibitory protein) (Serologically defined breast cancer antigen NY-BR-81) | Inhibitor of the PP1 regulatory subunit PPP1CA. |
| Q8TB24 | RIN3 | T518 | ochoa | Ras and Rab interactor 3 (Ras interaction/interference protein 3) | Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function. {ECO:0000269|PubMed:12972505, ECO:0000269|PubMed:21586568}. |
| Q8TB72 | PUM2 | T175 | ochoa | Pumilio homolog 2 (Pumilio-2) | 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:21397187). 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:22345517). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). 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). May regulate DCUN1D3 mRNA levels (PubMed:25349211). May support proliferation and self-renewal of stem cells. Binds specifically to miRNA MIR199A precursor, with PUM1, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233}. |
| Q8TDM6 | DLG5 | T946 | 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}. |
| Q8TEW8 | PARD3B | T341 | ochoa | Partitioning defective 3 homolog B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 19 protein) (PAR3-beta) (Partitioning defective 3-like protein) (PAR3-L protein) | Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. |
| Q8WUM9 | SLC20A1 | T422 | ochoa | Sodium-dependent phosphate transporter 1 (Gibbon ape leukemia virus receptor 1) (GLVR-1) (Leukemia virus receptor 1 homolog) (Phosphate transporter 1) (PiT-1) (Solute carrier family 20 member 1) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:16790504, PubMed:17494632, PubMed:19726692, PubMed:7929240, PubMed:8041748). May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification (PubMed:11009570). Essential for cell proliferation but this function is independent of its phosphate transporter activity (PubMed:19726692). {ECO:0000269|PubMed:11009570, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:19726692, ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:8041748}.; FUNCTION: (Microbial infection) May function as a retroviral receptor as it confers human cells susceptibility to infection to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine leukemia virus (10A1 MLV). {ECO:0000269|PubMed:12097582, ECO:0000269|PubMed:1309898, ECO:0000269|PubMed:2078500, ECO:0000269|PubMed:7966619}. |
| Q8WVM7 | STAG1 | T1097 | 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. |
| Q8WXE0 | CASKIN2 | T830 | ochoa | Caskin-2 (CASK-interacting protein 2) | None |
| Q8WY36 | BBX | T838 | 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}. |
| Q8WZA9 | IRGQ | T34 | ochoa | Immunity-related GTPase family Q protein | Autophagy receptor that specifically promotes clearance of misfolded MHC class I molecules by targeting them to the lysosome for degradation (PubMed:39481378). Acts as a molecular adapter that specifically recognizes and binds (1) misfolded MHC class I molecules following their ubiquitination, as well as (2) autophagy-related proteins, promoting the recruitment of misfolded MHC class I molecules to autophagy machinery for degradation (PubMed:39481378). Degradation of misfolded MHC class I molecules is essential to prevent accumulation of defective MHC class I complexes at the surface of CD8(+) T-cells and prevent a stronger T-cell-mediated response (PubMed:39481378). In contrast to other members of the family, does not show GTPase activity (PubMed:39481378). {ECO:0000269|PubMed:39481378}. |
| Q92521 | PIGB | T40 | ochoa | GPI alpha-1,2-mannosyltransferase 3 (EC 2.4.1.-) (GPI mannosyltransferase III) (GPI-MT-III) (Phosphatidylinositol-glycan biosynthesis class B protein) (PIG-B) | Alpha-1,2-mannosyltransferase that catalyzes the transfer of the third mannose, via an alpha-1,2 bond, from a dolichol-phosphate-mannose (Dol-P-Man) to an 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 intermediate to generate an 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 H6) and participates in the nineth step of the glycosylphosphatidylinositol-anchor biosynthesis (PubMed:8861954). May also add the third mannose to an alpha-D-Man-(1->6)-alpha-D-Man-(1->4)-alpha-D-GlcN-(1->6)-(1-radyl,2-acyl-sn-glycero-3-phospho)-2-acyl-inositol (also termed H3) intermediate generating an alpha-D-Man-(1->2)-alpha-D-Man-(1->6)-alpha-D-Man-(1->4)-alpha-D-GlcN-(1->6)-(1-radyl,2-acyl-sn-glycero-3-phospho)-2-acyl-inositol (also termed H4) (Probable). {ECO:0000269|PubMed:8861954, ECO:0000305|PubMed:17311586}. |
| Q92541 | RTF1 | T55 | ochoa | RNA polymerase-associated protein RTF1 homolog | 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. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity). {ECO:0000250, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:20178742}. |
| Q92576 | PHF3 | T101 | ochoa | PHD finger protein 3 | None |
| Q92826 | HOXB13 | T41 | psp | Homeobox protein Hox-B13 | Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000269|PubMed:28473536}. |
| Q92870 | APBB2 | T312 | ochoa | Amyloid beta precursor protein binding family B member 2 (Amyloid-beta (A4) precursor protein-binding family B member 2) (Protein Fe65-like 1) | Plays a role in the maintenance of lens transparency, and may also play a role in muscle cell strength (By similarity). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (By similarity). Activates transcription of APP (PubMed:14527950). {ECO:0000250|UniProtKB:Q9DBR4, ECO:0000269|PubMed:14527950}. |
| Q92903 | CDS1 | T41 | ochoa | Phosphatidate cytidylyltransferase 1 (EC 2.7.7.41) (CDP-DAG synthase 1) (CDP-DG synthase 1) (CDP-diacylglycerol synthase 1) (CDS 1) (CDP-diglyceride pyrophosphorylase 1) (CDP-diglyceride synthase 1) (CTP:phosphatidate cytidylyltransferase 1) | Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (PubMed:25375833, PubMed:9407135). Exhibits almost no acyl chain preference for PA, showing no discrimination for the sn-1/sn-2 acyl chain composition of PAs (PubMed:25375833). Plays an important role in regulating the growth of lipid droplets which are storage organelles at the center of lipid and energy homeostasis (PubMed:26946540, PubMed:31548309). Positively regulates the differentiation and development of adipocytes (By similarity). {ECO:0000250|UniProtKB:P98191, ECO:0000269|PubMed:25375833, ECO:0000269|PubMed:26946540, ECO:0000269|PubMed:31548309, ECO:0000269|PubMed:9407135}. |
| Q92917 | GPKOW | T24 | 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}. |
| Q92994 | BRF1 | T66 | 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 | T122 | 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}. |
| Q93052 | LPP | T325 | ochoa | Lipoma-preferred partner (LIM domain-containing preferred translocation partner in lipoma) | May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295}. |
| Q96BT3 | CENPT | T186 | ochoa | Centromere protein T (CENP-T) (Interphase centromere complex protein 22) | 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. Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis. {ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:21529714, ECO:0000269|PubMed:21695110}. |
| Q96BY6 | DOCK10 | T196 | 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}. |
| Q96CV9 | OPTN | T207 | 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}. |
| Q96DT7 | ZBTB10 | T646 | ochoa | Zinc finger and BTB domain-containing protein 10 (Zinc finger protein RIN ZF) | May be involved in transcriptional regulation. |
| Q96DX4 | RSPRY1 | T52 | ochoa | RING finger and SPRY domain-containing protein 1 | None |
| Q96EY5 | MVB12A | T130 | psp | Multivesicular body subunit 12A (CIN85/CD2AP family-binding protein) (ESCRT-I complex subunit MVB12A) (Protein FAM125A) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor. {ECO:0000269|PubMed:16895919}. |
| Q96HC4 | PDLIM5 | T373 | 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}. |
| Q96J84 | KIRREL1 | T732 | ochoa | Kin of IRRE-like protein 1 (Kin of irregular chiasm-like protein 1) (Nephrin-like protein 1) | Required for proper function of the glomerular filtration barrier. It is involved in the maintenance of a stable podocyte architecture with interdigitating foot processes connected by specialized cell-cell junctions, known as the slit diaphragm (PubMed:31472902). It is a signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:31472902}. |
| Q96K21 | ZFYVE19 | T291 | 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}. |
| Q96K83 | ZNF521 | T615 | ochoa | Zinc finger protein 521 (Early hematopoietic zinc finger protein) (LYST-interacting protein 3) | Transcription factor that can both act as an activator or a repressor depending on the context. Involved in BMP signaling and in the regulation of the immature compartment of the hematopoietic system. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved specification of B-cell lineage; this interaction preventing EBF1 to bind DNA and activate target genes. {ECO:0000269|PubMed:14630787}. |
| Q96T88 | UHRF1 | T117 | 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}. |
| Q99081 | TCF12 | T335 | 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}. |
| Q99497 | PARK7 | T125 | psp | Parkinson disease protein 7 (Maillard deglycase) (Oncogene DJ1) (Parkinsonism-associated deglycase) (Protein DJ-1) (DJ-1) (Protein/nucleic acid deglycase DJ-1) (EC 3.1.2.-, EC 3.5.1.-, EC 3.5.1.124) | Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:12796482, PubMed:17015834, PubMed:18711745, PubMed:19229105, PubMed:20304780, PubMed:25416785, PubMed:26995087, PubMed:28993701). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:12612053, PubMed:14749723, PubMed:15502874, PubMed:17015834, PubMed:18711745, PubMed:21097510). Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals (PubMed:25416785, PubMed:28596309). But this function is rebuted by other works (PubMed:27903648, PubMed:31653696). As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage (PubMed:25416785, PubMed:26995087, PubMed:28013050). Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair (PubMed:28596309). Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin (PubMed:30150385). Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels (PubMed:30150385, PubMed:30894531). Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093, PubMed:28993701, PubMed:31653696). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:16632486, PubMed:19229105). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (By similarity). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). {ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:18626009, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:26995087, ECO:0000269|PubMed:28013050, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:28993701, ECO:0000269|PubMed:30150385, ECO:0000269|PubMed:30894531, ECO:0000269|PubMed:9070310}. |
| Q99497 | PARK7 | T154 | psp | Parkinson disease protein 7 (Maillard deglycase) (Oncogene DJ1) (Parkinsonism-associated deglycase) (Protein DJ-1) (DJ-1) (Protein/nucleic acid deglycase DJ-1) (EC 3.1.2.-, EC 3.5.1.-, EC 3.5.1.124) | Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:12796482, PubMed:17015834, PubMed:18711745, PubMed:19229105, PubMed:20304780, PubMed:25416785, PubMed:26995087, PubMed:28993701). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:12612053, PubMed:14749723, PubMed:15502874, PubMed:17015834, PubMed:18711745, PubMed:21097510). Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals (PubMed:25416785, PubMed:28596309). But this function is rebuted by other works (PubMed:27903648, PubMed:31653696). As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage (PubMed:25416785, PubMed:26995087, PubMed:28013050). Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair (PubMed:28596309). Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin (PubMed:30150385). Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels (PubMed:30150385, PubMed:30894531). Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093, PubMed:28993701, PubMed:31653696). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:16390825). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:16632486, PubMed:19229105). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:18711745). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (By similarity). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (PubMed:18626009). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (By similarity). {ECO:0000250|UniProtKB:Q99LX0, ECO:0000269|PubMed:11477070, ECO:0000269|PubMed:12612053, ECO:0000269|PubMed:12855764, ECO:0000269|PubMed:12939276, ECO:0000269|PubMed:14749723, ECO:0000269|PubMed:15181200, ECO:0000269|PubMed:15502874, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:17015834, ECO:0000269|PubMed:18626009, ECO:0000269|PubMed:18711745, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20186336, ECO:0000269|PubMed:20304780, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22523093, ECO:0000269|PubMed:23792957, ECO:0000269|PubMed:23847046, ECO:0000269|PubMed:25416785, ECO:0000269|PubMed:26995087, ECO:0000269|PubMed:28013050, ECO:0000269|PubMed:28596309, ECO:0000269|PubMed:28993701, ECO:0000269|PubMed:30150385, ECO:0000269|PubMed:30894531, ECO:0000269|PubMed:9070310}. |
| Q99832 | CCT7 | T371 | 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}. |
| Q9BPX5 | ARPC5L | T68 | ochoa | Actin-related protein 2/3 complex subunit 5-like protein (Arp2/3 complex 16 kDa subunit 2) (ARC16-2) | May function as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. |
| Q9BQE3 | TUBA1C | T51 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C 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. |
| Q9BRD0 | BUD13 | T251 | 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}. |
| Q9BT23 | LIMD2 | T23 | ochoa | LIM domain-containing protein 2 | Acts as an activator of the protein-kinase ILK, thereby regulating cell motility (PubMed:24590809). {ECO:0000269|PubMed:24590809}. |
| Q9BTK6 | PAGR1 | T25 | ochoa | PAXIP1-associated glutamate-rich protein 1 (Glutamate-rich coactivator interacting with SRC1) (GAS) (PAXIP1-associated protein 1) (PTIP-associated protein 1) | Its association with the histone methyltransferase MLL2/MLL3 complex is suggesting a role in epigenetic transcriptional activation. However, in association with PAXIP1/PTIP is proposed to function at least in part independently of the MLL2/MLL3 complex. Proposed to be recruited by PAXIP1 to sites of DNA damage where the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage independently of the MLL2/MLL3 complex (PubMed:19124460). However, its function in DNA damage has been questioned (By similarity). During immunoglobulin class switching in activated B-cells is involved in transcription regulation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus independently of the MLL2/MLL3 complex (By similarity). Involved in both estrogen receptor-regulated gene transcription and estrogen-stimulated G1/S cell-cycle transition (PubMed:19039327). Acts as a transcriptional cofactor for nuclear hormone receptors. Inhibits the induction properties of several steroid receptors such as NR3C1, AR and PPARG; the mechanism of inhibition appears to be gene-dependent (PubMed:23161582). {ECO:0000250|UniProtKB:Q99L02, ECO:0000269|PubMed:19039327, ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:23161582, ECO:0000305}. |
| Q9BUJ2 | HNRNPUL1 | T209 | 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}. |
| Q9BVA1 | TUBB2B | T55 | 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}. |
| Q9BVV6 | KIAA0586 | T1104 | ochoa | Protein TALPID3 | Required for ciliogenesis and sonic hedgehog/SHH signaling. Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1. May play a role in early ciliogenesis in the disappearance of centriolar satellites that preceeds ciliary vesicle formation (PubMed:24421332). Involved in regulation of cell intracellular organization. Involved in regulation of cell polarity (By similarity). Required for asymmetrical localization of CEP120 to daughter centrioles (By similarity). {ECO:0000250|UniProtKB:E9PV87, ECO:0000250|UniProtKB:Q1G7G9, ECO:0000269|PubMed:24421332}. |
| Q9BX66 | SORBS1 | T150 | ochoa | Sorbin and SH3 domain-containing protein 1 (Ponsin) (SH3 domain protein 5) (SH3P12) (c-Cbl-associated protein) (CAP) | Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). {ECO:0000250|UniProtKB:Q62417}. |
| Q9BXS5 | AP1M1 | T223 | ochoa | AP-1 complex subunit mu-1 (AP-mu chain family member mu1A) (Adaptor protein complex AP-1 subunit mu-1) (Adaptor-related protein complex 1 subunit mu-1) (Clathrin assembly protein complex 1 mu-1 medium chain 1) (Clathrin coat assembly protein AP47) (Clathrin coat-associated protein AP47) (Golgi adaptor HA1/AP1 adaptin mu-1 subunit) (Mu-adaptin 1) (Mu1A-adaptin) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. |
| Q9BY77 | POLDIP3 | T45 | ochoa | Polymerase delta-interacting protein 3 (46 kDa DNA polymerase delta interaction protein) (p46) (S6K1 Aly/REF-like target) (SKAR) | Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex. {ECO:0000269|PubMed:18423201, ECO:0000269|PubMed:22928037}. |
| Q9BYB0 | SHANK3 | T1027 | 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}. |
| Q9C0C2 | TNKS1BP1 | T833 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0D5 | TANC1 | T347 | 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 | T1585 | 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}. |
| Q9GZV5 | WWTR1 | T98 | 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}. |
| Q9H2C2 | ARV1 | T22 | ochoa | Protein ARV1 (hARV1) | Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis (PubMed:11063737, PubMed:12145310, PubMed:20663892). Participates in sterol transport out of the ER and distribution into plasma membranes (PubMed:20663892). {ECO:0000269|PubMed:11063737, ECO:0000269|PubMed:12145310, ECO:0000269|PubMed:20663892}. |
| Q9H6F5 | CCDC86 | T204 | ochoa | Coiled-coil domain-containing protein 86 (Cytokine-induced protein with coiled-coil domain) | Required for proper chromosome segregation during mitosis and error-free mitotic progression. {ECO:0000269|PubMed:36695333}. |
| Q9HB75 | PIDD1 | T788 | psp | p53-induced death domain-containing protein 1 (EC 3.4.21.-) (Leucine-rich repeat and death domain-containing protein) [Cleaved into: PIDD-N; PIDD-C; PIDD-CC] | Component of the DNA damage/stress response pathway that functions downstream of p53/TP53 and can either promote cell survival or apoptosis (PubMed:10973264, PubMed:15073321, PubMed:16360037, PubMed:17159900). Associated with CRADD and the CASP2 caspase, it forms the PIDDosome a complex that activates CASP2 and triggers apoptosis (PubMed:15073321, PubMed:17159900). Associated with IKBKG and RIPK1, it enhances sumoylation and ubiquitination of IKBKG which is important for activation of the transcription factor NF-kappa-B (PubMed:16360037, PubMed:17159900). {ECO:0000269|PubMed:10973264, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:16360037, ECO:0000269|PubMed:17159900}. |
| Q9HD26 | GOPC | T437 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (Fused in glioblastoma) (PDZ protein interacting specifically with TC10) (PIST) | Plays a role in intracellular protein trafficking and degradation (PubMed:11707463, PubMed:14570915, PubMed:15358775). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (By similarity). May also regulate the intracellular trafficking of the ADR1B receptor (PubMed:15358775). May play a role in autophagy (By similarity). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989). Overexpression results in CFTR intracellular retention and lysosomaldegradation in the lysosomes (PubMed:11707463, PubMed:14570915). {ECO:0000250|UniProtKB:Q8BH60, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:14570915, ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:23818989}. |
| Q9NP74 | PALMD | T531 | ochoa | Palmdelphin (Paralemmin-like protein) | None |
| Q9NQS1 | AVEN | T98 | ochoa | Cell death regulator Aven | Protects against apoptosis mediated by Apaf-1. |
| Q9NQV6 | PRDM10 | T828 | 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}. |
| Q9NR33 | POLE4 | T77 | ochoa | DNA polymerase epsilon subunit 4 (DNA polymerase II subunit 4) (DNA polymerase epsilon subunit p12) | Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity). {ECO:0000250|UniProtKB:P27344, ECO:0000269|PubMed:10801849}. |
| Q9NRP7 | STK36 | T154 | ochoa | Serine/threonine-protein kinase 36 (EC 2.7.11.1) (Fused homolog) | Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur (PubMed:10806483). Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia. {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:28543983}. |
| Q9NTK5 | OLA1 | T124 | psp | Obg-like ATPase 1 (DNA damage-regulated overexpressed in cancer 45) (DOC45) (GTP-binding protein 9) | Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP. {ECO:0000255|HAMAP-Rule:MF_03167}. |
| Q9NY65 | TUBA8 | T381 | 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. |
| Q9NY65 | TUBA8 | T382 | 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. |
| Q9NZP8 | C1RL | T141 | ochoa | Complement C1r subcomponent-like protein (C1r-LP) (C1r-like protein) (EC 3.4.21.-) (C1r-like serine protease analog protein) (CLSPa) | Mediates the proteolytic cleavage of HP/haptoglobin in the endoplasmic reticulum. {ECO:0000269|PubMed:15358180, ECO:0000269|PubMed:15385675, ECO:0000269|PubMed:15527420}. |
| Q9P206 | NHSL3 | T416 | ochoa | NHS-like protein 3 | Able to directly activate the TNF-NFkappaB signaling pathway. {ECO:0000269|PubMed:32854746}. |
| Q9P265 | DIP2B | T283 | 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}. |
| Q9P270 | SLAIN2 | T95 | 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}. |
| Q9P2Q2 | FRMD4A | T893 | 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 | T612 | 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}. |
| Q9UBS8 | RNF14 | T165 | 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}. |
| Q9UGN5 | PARP2 | T28 | ochoa | Poly [ADP-ribose] polymerase 2 (PARP-2) (hPARP-2) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 2) (ARTD2) (DNA ADP-ribosyltransferase PARP2) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 2) (ADPRT-2) (Poly[ADP-ribose] synthase 2) (pADPRT-2) (Protein poly-ADP-ribosyltransferase PARP2) (EC 2.4.2.-) | Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, PubMed:32028527, PubMed:32939087, PubMed:34108479, PubMed:34486521, PubMed:34874266). Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:25043379, PubMed:30104678, PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (PubMed:28190768, PubMed:32028527, PubMed:34108479, PubMed:34486521, PubMed:34874266). PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:10364231, PubMed:32939087, PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (PubMed:30104678). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex (PubMed:27471034, PubMed:29361132). {ECO:0000269|PubMed:10364231, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29361132, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266}. |
| Q9UHW9 | SLC12A6 | T1048 | psp | Solute carrier family 12 member 6 (Electroneutral potassium-chloride cotransporter 3) (K-Cl cotransporter 3) | [Isoform 1]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10600773, PubMed:11551954, PubMed:16048901, PubMed:18566107, PubMed:19665974, PubMed:21628467, PubMed:27485015). May contribute to cell volume homeostasis in single cells (PubMed:16048901, PubMed:27485015). {ECO:0000269|PubMed:10600773, ECO:0000269|PubMed:11551954, ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:18566107, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21628467, ECO:0000269|PubMed:27485015, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 2]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:33199848, PubMed:34031912). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:33199848, ECO:0000269|PubMed:34031912, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 3]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 4]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 5]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 6]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}. |
| Q9UIG0 | BAZ1B | T833 | 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}. |
| Q9UJA5 | TRMT6 | T468 | ochoa | tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (mRNA methyladenosine-N(1)-methyltransferase non-catalytic subunit TRM6) (tRNA(m1A58)-methyltransferase subunit TRM6) (tRNA(m1A58)MTase subunit TRM6) | Substrate-binding subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA (PubMed:16043508). Together with the TRMT61A catalytic subunit, part of a mRNA N(1)-methyltransferase complex that mediates methylation of adenosine residues at the N(1) position of a small subset of mRNAs: N(1) methylation takes place in tRNA T-loop-like structures of mRNAs and is only present at low stoichiometries (PubMed:29072297, PubMed:29107537). {ECO:0000269|PubMed:16043508, ECO:0000269|PubMed:29072297, ECO:0000269|PubMed:29107537}. |
| Q9UKG1 | APPL1 | T493 | ochoa | 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}. |
| Q9UKS6 | PACSIN3 | T306 | ochoa | Protein kinase C and casein kinase substrate in neurons protein 3 (SH3 domain-containing protein 6511) | Plays a role in endocytosis and regulates internalization of plasma membrane proteins. Overexpression impairs internalization of SLC2A1/GLUT1 and TRPV4 and increases the levels of SLC2A1/GLUT1 and TRPV4 at the cell membrane. Inhibits the TRPV4 calcium channel activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:11082044}. |
| Q9ULH0 | KIDINS220 | T1528 | ochoa | Kinase D-interacting substrate of 220 kDa (Ankyrin repeat-rich membrane-spanning protein) | Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration (By similarity). Modulates stress-induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway. {ECO:0000250, ECO:0000269|PubMed:18089783}. |
| Q9UNS1 | TIMELESS | T115 | 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}. |
| Q9UPQ9 | TNRC6B | T1464 | 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}. |
| Q9UPU9 | SAMD4A | T583 | 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}. |
| Q9UQ35 | SRRM2 | T2170 | 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}. |
| Q9UQM7 | CAMK2A | T336 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation (PubMed:14722083). Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023). In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (PubMed:35568036). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}. |
| Q9UQP3 | TNN | T941 | ochoa | Tenascin-N (TN-N) (Tenascin-W) (TN-W) | Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1 (By similarity) (PubMed:17909022). Involved in neurite outgrowth and cell migration in hippocampal explants (By similarity). During endochondral bone formation, inhibits proliferation and differentiation of proteoblasts mediated by canonical WNT signaling (By similarity). In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (PubMed:19884327). Expressed in most mammary tumors, may facilitate tumorigenesis by supporting the migratory behavior of breast cancer cells (PubMed:17909022). {ECO:0000250|UniProtKB:Q80YX1, ECO:0000250|UniProtKB:Q80Z71, ECO:0000269|PubMed:17909022, ECO:0000269|PubMed:19884327}. |
| Q9UQR1 | ZNF148 | T694 | ochoa | Zinc finger protein 148 (Transcription factor ZBP-89) (Zinc finger DNA-binding protein 89) | Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes. |
| Q9Y266 | NUDC | T40 | psp | 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}. |
| Q9Y286 | SIGLEC7 | T411 | 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}. |
| Q9Y2E4 | DIP2C | T264 | ochoa | Disco-interacting protein 2 homolog C (DIP2 homolog C) | None |
| Q9Y2K5 | R3HDM2 | T856 | ochoa | R3H domain-containing protein 2 | None |
| Q9Y2K6 | USP20 | T352 | 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 | T537 | 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}. |
| Q9Y2Y9 | KLF13 | T43 | 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}. |
| Q9Y3E1 | HDGFL3 | T110 | ochoa | Hepatoma-derived growth factor-related protein 3 (HRP-3) (Hepatoma-derived growth factor 2) (HDGF-2) | Enhances DNA synthesis and may play a role in cell proliferation. {ECO:0000269|PubMed:10581169}. |
| Q9Y3P8 | SIT1 | T98 | ochoa | Signaling threshold-regulating transmembrane adapter 1 (SHP2-interacting transmembrane adapter protein) (Suppression-inducing transmembrane adapter 1) (gp30/40) | Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells. Involved in positive selection of T-cells. {ECO:0000269|PubMed:10209036}. |
| Q9Y446 | PKP3 | T207 | 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 | T242 | 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}. |
| Q9Y478 | PRKAB1 | T148 | psp | 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). |
| Q9Y490 | TLN1 | T1502 | 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}. |
| Q9Y4G6 | TLN2 | T1843 | 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}. |
| Q9Y6A5 | TACC3 | T437 | 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}. |
| Q9Y6I3 | EPN1 | T412 | ochoa | Epsin-1 (EH domain-binding mitotic phosphoprotein) (EPS-15-interacting protein 1) | Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis (PubMed:10393179, PubMed:10557078). {ECO:0000250|UniProtKB:O88339, ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10557078}. |
| Q9Y6J0 | CABIN1 | T2097 | 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}. |
| Q9Y6Q5 | AP1M2 | T70 | ochoa | AP-1 complex subunit mu-2 (AP-mu chain family member mu1B) (Adaptor protein complex AP-1 subunit mu-2) (Adaptor-related protein complex 1 subunit mu-2) (Clathrin assembly protein complex 1 mu-2 medium chain 2) (Golgi adaptor HA1/AP1 adaptin mu-2 subunit) (Mu-adaptin 2) (Mu1B-adaptin) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. |
| Q9Y6Q9 | NCOA3 | T1114 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| P08238 | HSP90AB1 | T85 | Sugiyama | 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}. |
| P62942 | FKBP1A | T28 | Sugiyama | Peptidyl-prolyl cis-trans isomerase FKBP1A (PPIase FKBP1A) (EC 5.2.1.8) (12 kDa FK506-binding protein) (12 kDa FKBP) (FKBP-12) (Calstabin-1) (FK506-binding protein 1A) (FKBP-1A) (Immunophilin FKBP12) (Rotamase) | Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. {ECO:0000269|PubMed:16720724, ECO:0000269|PubMed:1696686, ECO:0000269|PubMed:1701173, ECO:0000269|PubMed:9233797}. |
| O00170 | AIP | T48 | Sugiyama | AH receptor-interacting protein (AIP) (Aryl-hydrocarbon receptor-interacting protein) (HBV X-associated protein 2) (XAP-2) (Immunophilin homolog ARA9) | May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.; FUNCTION: Cellular negative regulator of the hepatitis B virus (HBV) X protein. |
| P08195 | SLC3A2 | T275 | 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}. |
| Q15084 | PDIA6 | T166 | 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}. |
| P05198 | EIF2S1 | T284 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 1 (Eukaryotic translation initiation factor 2 subunit alpha) (eIF-2-alpha) (eIF-2A) (eIF-2alpha) (eIF2-alpha) | 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:16289705, PubMed:38340717). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC) (PubMed:16289705). 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 (PubMed:16289705). 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 eIF2B (PubMed:16289705). EIF2S1/eIF2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF2-alpha in a global protein synthesis inhibitor, leading to an attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:19131336, PubMed:33384352, PubMed:38340717). EIF2S1/eIF2-alpha also acts as an activator of mitophagy in response to mitochondrial damage: phosphorylation by EIF2AK1/HRI promotes relocalization to the mitochondrial surface, thereby triggering PRKN-independent mitophagy (PubMed:38340717). {ECO:0000269|PubMed:16289705, ECO:0000269|PubMed:19131336, ECO:0000269|PubMed:33384352, ECO:0000269|PubMed:38340717}. |
| P06733 | ENO1 | T55 | 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}. |
| P60174 | TPI1 | T90 | 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}. |
| P13639 | EEF2 | T484 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| P60174 | TPI1 | T28 | 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}. |
| Q06830 | PRDX1 | T111 | Sugiyama | 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}. |
| Q14157 | UBAP2L | T23 | Sugiyama | 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}. |
| Q15293 | RCN1 | T163 | Sugiyama | Reticulocalbin-1 | May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment. |
| Q96G46 | DUS3L | T176 | Sugiyama | tRNA-dihydrouridine(47) synthase [NAD(P)(+)]-like (EC 1.3.1.89) (mRNA-dihydrouridine synthase DUS3L) (EC 1.3.1.-) (tRNA-dihydrouridine synthase 3-like) | Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:34556860). Mainly modifies the uridine in position 47 (U47) in the D-loop of most cytoplasmic tRNAs (PubMed:34556860). Also able to mediate the formation of dihydrouridine in some mRNAs, thereby regulating their translation (PubMed:34556860). {ECO:0000269|PubMed:34556860}. |
| Q9NZZ3 | CHMP5 | T23 | Sugiyama | Charged multivesicular body protein 5 (Chromatin-modifying protein 5) (SNF7 domain-containing protein 2) (Vacuolar protein sorting-associated protein 60) (Vps60) (hVps60) | 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) (PubMed:14519844). 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 HIV-1 p6- and p9-dependent virus release (PubMed:14519844). {ECO:0000269|PubMed:14519844}. |
| P39023 | RPL3 | T305 | Sugiyama | Large ribosomal subunit protein uL3 (60S ribosomal protein L3) (HIV-1 TAR RNA-binding protein B) (TARBP-B) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547, PubMed:35674491). 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}. |
| O15075 | DCLK1 | T46 | Sugiyama | Serine/threonine-protein kinase DCLK1 (EC 2.7.11.1) (Doublecortin domain-containing protein 3A) (Doublecortin-like and CAM kinase-like 1) (Doublecortin-like kinase 1) | Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system. |
| O15111 | CHUK | T392 | Sugiyama | 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}. |
| O96019 | ACTL6A | T67 | Sugiyama | 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}. |
| P13639 | EEF2 | T735 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| P11142 | HSPA8 | T47 | Sugiyama | 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}. |
| P17066 | HSPA6 | T49 | Sugiyama | Heat shock 70 kDa protein 6 (Heat shock 70 kDa protein B') (Heat shock protein family A member 6) | 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). {ECO:0000303|PubMed:26865365}. |
| P34931 | HSPA1L | T49 | Sugiyama | Heat shock 70 kDa protein 1-like (Heat shock 70 kDa protein 1L) (Heat shock 70 kDa protein 1-Hom) (HSP70-Hom) (Heat shock protein family A member 1L) | 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). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810). {ECO:0000269|PubMed:24270810, ECO:0000303|PubMed:26865365}. |
| P48741 | HSPA7 | T49 | Sugiyama | Putative heat shock 70 kDa protein 7 (Heat shock 70 kDa protein B) (Heat shock protein family A member 7) | None |
| P54652 | HSPA2 | T48 | Sugiyama | 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}. |
| P00390 | GSR | T365 | Sugiyama | Glutathione reductase, mitochondrial (GR) (GRase) (EC 1.8.1.7) | Catalyzes the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH). Constitutes the major mechanism to maintain a high GSH:GSSG ratio in the cytosol. {ECO:0000269|PubMed:17185460}. |
| O43781 | DYRK3 | T34 | Sugiyama | Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC 2.7.12.1) (Regulatory erythroid kinase) (REDK) | Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:29634919, PubMed:9748265). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}. |
| O60245 | PCDH7 | T251 | Sugiyama | Protocadherin-7 (Brain-heart protocadherin) (BH-Pcdh) | None |
| P07237 | P4HB | T428 | Sugiyama | Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) | This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}. |
| P26373 | RPL13 | T24 | Sugiyama | Large ribosomal subunit protein eL13 (60S ribosomal protein L13) (Breast basic conserved protein 1) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:31630789, PubMed:32669547). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (Probable). 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 (Probable). 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 (Probable). As part of the LSU, it is probably required for its formation and the maturation of rRNAs (PubMed:31630789). Plays a role in bone development (PubMed:31630789). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:31630789, ECO:0000269|PubMed:32669547}. |
| Q13442 | PDAP1 | T93 | Sugiyama | 28 kDa heat- and acid-stable phosphoprotein (PDGF-associated protein) (PAP) (PDGFA-associated protein 1) (PAP1) | Enhances PDGFA-stimulated cell growth in fibroblasts, but inhibits the mitogenic effect of PDGFB. {ECO:0000250}. |
| O75582 | RPS6KA5 | T38 | 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}. |
| P78371 | CCT2 | T242 | 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}. |
| O95834 | EML2 | T355 | Sugiyama | Echinoderm microtubule-associated protein-like 2 (EMAP-2) (HuEMAP-2) | Tubulin binding protein that inhibits microtubule nucleation and growth, resulting in shorter microtubules. {ECO:0000269|PubMed:11694528}. |
| P48643 | CCT5 | T47 | Sugiyama | T-complex protein 1 subunit epsilon (TCP-1-epsilon) (EC 3.6.1.-) (CCT-epsilon) (Chaperonin containing T-complex polypeptide 1 subunit 5) | 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}. |
| P78406 | RAE1 | T77 | Sugiyama | mRNA export factor RAE1 (Rae1 protein homolog) (mRNA-associated protein mrnp 41) | Acts as a mRNA export factor involved in nucleocytoplasmic transport (PubMed:20498086, PubMed:33849972). Plays a role in mitotic bipolar spindle formation (PubMed:17172455). May function in attaching cytoplasmic mRNPs to the cytoskeleton both directly or indirectly (PubMed:17172455). {ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:20498086, ECO:0000269|PubMed:33849972}. |
| Q58FG1 | HSP90AA4P | T30 | Sugiyama | Putative heat shock protein HSP 90-alpha A4 (Heat shock 90 kDa protein 1 alpha-like 2) (Heat shock protein 90-alpha D) (Heat shock protein 90Ad) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q9Y2X3 | NOP58 | T427 | Sugiyama | 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}. |
| P00519 | ABL1 | T389 | 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}. |
| P30085 | CMPK1 | T30 | Sugiyama | UMP-CMP kinase (EC 2.7.4.14) (Deoxycytidylate kinase) (CK) (dCMP kinase) (Nucleoside-diphosphate kinase) (EC 2.7.4.6) (Uridine monophosphate/cytidine monophosphate kinase) (UMP/CMP kinase) (UMP/CMPK) | Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity. {ECO:0000255|HAMAP-Rule:MF_03172, ECO:0000269|PubMed:10462544, ECO:0000269|PubMed:11912132, ECO:0000269|PubMed:23416111}. |
| P42684 | ABL2 | T435 | Sugiyama | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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. 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). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| Q13228 | SELENBP1 | T38 | Sugiyama | 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}. |
| Q9NQW7 | XPNPEP1 | T405 | Sugiyama | 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}. |
| P04075 | ALDOA | T65 | Sugiyama | 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}. |
| Q9UG63 | ABCF2 | T307 | Sugiyama | ATP-binding cassette sub-family F member 2 (Iron-inhibited ABC transporter 2) | None |
| P21333 | FLNA | T1307 | Sugiyama | 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}. |
| P16234 | PDGFRA | T855 | 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}. |
| P06213 | INSR | T1362 | SIGNOR|EPSD | 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}. |
| O14979 | HNRNPDL | T165 | Sugiyama | Heterogeneous nuclear ribonucleoprotein D-like (hnRNP D-like) (hnRNP DL) (AU-rich element RNA-binding factor) (JKT41-binding protein) (Protein laAUF1) | Acts as a transcriptional regulator. Promotes transcription repression. Promotes transcription activation in differentiated myotubes (By similarity). Binds to double- and single-stranded DNA sequences. Binds to the transcription suppressor CATR sequence of the COX5B promoter (By similarity). 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. Binds both to nuclear and cytoplasmic poly(A) mRNAs. Binds to poly(G) and poly(A), but not to poly(U) or poly(C) RNA homopolymers. Binds to the 5'-ACUAGC-3' RNA consensus sequence. {ECO:0000250, ECO:0000269|PubMed:9538234}. |
| P23443 | RPS6KB1 | T77 | Sugiyama | Ribosomal protein S6 kinase beta-1 (S6K-beta-1) (S6K1) (EC 2.7.11.1) (70 kDa ribosomal protein S6 kinase 1) (P70S6K1) (p70-S6K 1) (Ribosomal protein S6 kinase I) (Serine/threonine-protein kinase 14A) (p70 ribosomal S6 kinase alpha) (p70 S6 kinase alpha) (p70 S6K-alpha) (p70 S6KA) | Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating MAPKAP1/SIN1, MTOR and RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (PubMed:15899889, PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (By similarity). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (PubMed:17936702). The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function (PubMed:17936702). Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (PubMed:17052453). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239). {ECO:0000250|UniProtKB:P67999, ECO:0000250|UniProtKB:Q8BSK8, ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500, ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:15899889, ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:28178239}. |
| Q86X55 | CARM1 | T39 | Sugiyama | Histone-arginine methyltransferase CARM1 (EC 2.1.1.319) (Coactivator-associated arginine methyltransferase 1) (Protein arginine N-methyltransferase 4) | Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability (PubMed:12237300, PubMed:16497732, PubMed:19405910). Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activation of transcription via chromatin remodeling (PubMed:12237300, PubMed:16497732, PubMed:19405910). During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription (By similarity). During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C (By similarity). During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B (By similarity). Acts as a coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue (By similarity). Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors (By similarity). Also seems to be involved in p53/TP53 transcriptional activation (By similarity). Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation (PubMed:15731352). Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs (By similarity). Acts as a transcriptional coactivator of ACACA/acetyl-CoA carboxylase by enriching H3R17 methylation at its promoter, thereby positively regulating fatty acid synthesis (By similarity). Independently of its methyltransferase activity, involved in replication fork progression: promotes PARP1 recruitment to replication forks, leading to poly-ADP-ribosylation of chromatin at replication forks and reduced fork speed (PubMed:33412112). {ECO:0000250|UniProtKB:Q9WVG6, ECO:0000269|PubMed:12237300, ECO:0000269|PubMed:15731352, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:19405910, ECO:0000269|PubMed:33412112}. |
| Q02156 | PRKCE | T175 | Sugiyama | 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}. |
| P30740 | SERPINB1 | T111 | Sugiyama | Leukocyte elastase inhibitor (LEI) (Monocyte/neutrophil elastase inhibitor) (EI) (M/NEI) (Peptidase inhibitor 2) (PI-2) (Serpin B1) | Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis (PubMed:30692621). Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3 (PubMed:11747453, PubMed:30692621). Also acts as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity (PubMed:23269243). During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621). When secreted, promotes the proliferation of beta-cells via its protease inhibitory function (PubMed:26701651). {ECO:0000269|PubMed:11747453, ECO:0000269|PubMed:23269243, ECO:0000269|PubMed:26701651, ECO:0000269|PubMed:30692621}. |
| P29597 | TYK2 | T923 | Sugiyama | 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}. |
| Q14247 | CTTN | T328 | Sugiyama | 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}. |
| P35968 | KDR | T926 | Sugiyama | Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}. |
| P23381 | WARS1 | T362 | 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}. |
| P36896 | ACVR1B | T364 | Sugiyama | Activin receptor type-1B (EC 2.7.11.30) (Activin receptor type IB) (ACTR-IB) (Activin receptor-like kinase 4) (ALK-4) (Serine/threonine-protein kinase receptor R2) (SKR2) | Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, ECO:0000269|PubMed:9892009}. |
| P45985 | MAP2K4 | T56 | Sugiyama | Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}. |
| Q68BL8 | OLFML2B | T509 | Sugiyama | Olfactomedin-like protein 2B (Photomedin-2) | None |
| P49760 | CLK2 | T173 | Sugiyama | Dual specificity protein kinase CLK2 (EC 2.7.12.1) (CDC-like kinase 2) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Phosphorylates PAGE4 at several serine and threonine residues and this phosphorylation attenuates the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:28289210). {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:28289210, ECO:0000269|PubMed:8910305, ECO:0000269|PubMed:9637771}. |
| Q14566 | MCM6 | T278 | Sugiyama | 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}. |
| Q99519 | NEU1 | T89 | Sugiyama | Sialidase-1 (EC 3.2.1.18) (Acetylneuraminyl hydrolase) (G9 sialidase) (Lysosomal sialidase) (N-acetyl-alpha-neuraminidase 1) | Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage. {ECO:0000269|PubMed:25153125, ECO:0000269|PubMed:8985184}. |
| P51813 | BMX | T331 | Sugiyama | Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) | Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}. |
| P30101 | PDIA3 | T437 | Sugiyama | Protein disulfide-isomerase A3 (EC 5.3.4.1) (58 kDa glucose-regulated protein) (58 kDa microsomal protein) (p58) (Disulfide isomerase ER-60) (Endoplasmic reticulum resident protein 57) (ER protein 57) (ERp57) (Endoplasmic reticulum resident protein 60) (ER protein 60) (ERp60) | Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone (PubMed:11825568, PubMed:16193070, PubMed:27897272, PubMed:36104323, PubMed:7487104). Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity (PubMed:35948544, PubMed:36104323). {ECO:0000269|PubMed:11825568, ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:27897272, ECO:0000269|PubMed:35948544, ECO:0000269|PubMed:36104323, ECO:0000269|PubMed:7487104}. |
| Q13409 | DYNC1I2 | T617 | Sugiyama | 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}. |
| O00267 | SUPT5H | T709 | Sugiyama | 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}. |
| P52565 | ARHGDIA | T142 | Sugiyama | 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 | T91 | SIGNOR | 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}. |
| Q86UE4 | MTDH | T317 | Sugiyama | 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}. |
| P53671 | LIMK2 | T278 | 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}. |
| P09972 | ALDOC | T123 | Sugiyama | Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) | None |
| P25325 | MPST | T208 | Sugiyama | 3-mercaptopyruvate sulfurtransferase (MST) (EC 2.8.1.2) | Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions. {ECO:0000250|UniProtKB:P97532}. |
| P43490 | NAMPT | T249 | Sugiyama | Nicotinamide phosphoribosyltransferase (NAmPRTase) (Nampt) (EC 2.4.2.12) (Pre-B-cell colony-enhancing factor 1) (Pre-B cell-enhancing factor) (Visfatin) | Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity). {ECO:0000250|UniProtKB:Q99KQ4, ECO:0000269|PubMed:24130902}. |
| Q14677 | CLINT1 | T265 | Sugiyama | 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}. |
| Q00534 | CDK6 | T70 | Sugiyama | Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) | Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}. |
| P04406 | GAPDH | T19 | Sugiyama | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment 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 (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| Q06187 | BTK | T316 | 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}. |
| Q08881 | ITK | T274 | Sugiyama | Tyrosine-protein kinase ITK/TSK (EC 2.7.10.2) (Interleukin-2-inducible T-cell kinase) (IL-2-inducible T-cell kinase) (Kinase EMT) (T-cell-specific kinase) (Tyrosine-protein kinase Lyk) | Tyrosine kinase that plays an essential role 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 lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and 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. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation (PubMed:12186560, PubMed:12682224, PubMed:21725281). Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (By similarity). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity). {ECO:0000250|UniProtKB:Q03526, ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}. |
| P99999 | CYCS | T41 | Sugiyama | Cytochrome c | Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.; FUNCTION: Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases. |
| P30622 | CLIP1 | T260 | Sugiyama | 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}. |
| Q9NQE9 | HINT3 | T47 | Sugiyama | Adenosine 5'-monophosphoramidase HINT3 (EC 3.9.1.-) (Histidine triad nucleotide-binding protein 3) (HINT-3) | 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:17870088). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase (PubMed:17870088). Hydrolyzes 3-indolepropionic acyl-adenylate and fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17870088). {ECO:0000269|PubMed:17870088}. |
| P13798 | APEH | T36 | Sugiyama | Acylamino-acid-releasing enzyme (AARE) (EC 3.4.19.1) (Acyl-peptide hydrolase) (APH) (Acylaminoacyl-peptidase) (Oxidized protein hydrolase) (OPH) | This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus (PubMed:10719179, PubMed:1740429, PubMed:2006156). It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Also, involved in the degradation of oxidized and glycated proteins (PubMed:10719179). {ECO:0000250|UniProtKB:P13676, ECO:0000269|PubMed:10719179, ECO:0000269|PubMed:1740429, ECO:0000269|PubMed:2006156}. |
| Q14012 | CAMK1 | T339 | Sugiyama | 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}. |
| Q14164 | IKBKE | T156 | Sugiyama | Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i) | Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}. |
| Q15303 | ERBB4 | T1211 | Sugiyama | 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}. |
| P00568 | AK1 | T39 | Sugiyama | Adenylate kinase isoenzyme 1 (AK 1) (EC 2.7.4.3) (EC 2.7.4.4) (EC 2.7.4.6) (ATP-AMP transphosphorylase 1) (ATP:AMP phosphotransferase) (Adenylate monophosphate kinase) (Myokinase) | Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism (By similarity) (PubMed:21080915, PubMed:23416111, PubMed:2542324). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (By similarity). {ECO:0000250|UniProtKB:P05081, ECO:0000255|HAMAP-Rule:MF_03171, ECO:0000269|PubMed:21080915, ECO:0000269|PubMed:23416111, ECO:0000269|PubMed:2542324}. |
| Q15569 | TESK1 | T97 | Sugiyama | 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}. |
| P62913 | RPL11 | T44 | 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}. |
| P17544 | ATF7 | T55 | Sugiyama | Cyclic AMP-dependent transcription factor ATF-7 (cAMP-dependent transcription factor ATF-7) (Activating transcription factor 7) (Transcription factor ATF-A) | Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation (PubMed:29490055). In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes (By similarity). Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation (By similarity). In response to TNF-alpha, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening (PubMed:29490055). Also plays a role in maintaining epithelial regenerative capacity and protecting against cell death during intestinal epithelial damage and repair (By similarity). {ECO:0000250|UniProtKB:Q8R0S1, ECO:0000269|PubMed:29490055}.; FUNCTION: [Isoform 4]: Acts as a dominant repressor of the E-selectin/NF-ELAM1/delta-A promoter.; FUNCTION: [Isoform 5]: Acts as a negative regulator, inhibiting both ATF2 and ATF7 transcriptional activities. It may exert these effects by sequestrating in the cytoplasm the Thr-53 phosphorylating kinase, preventing activation. {ECO:0000269|PubMed:21858082}. |
| Q9HCN8 | SDF2L1 | T196 | Sugiyama | Stromal cell-derived factor 2-like protein 1 (SDF2-like protein 1) (PWP1-interacting protein 8) | None |
| P28066 | PSMA5 | T161 | 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}. |
| Q00796 | SORD | T75 | Sugiyama | Sorbitol dehydrogenase (SDH) (EC 1.1.1.-) ((R,R)-butanediol dehydrogenase) (EC 1.1.1.4) (L-iditol 2-dehydrogenase) (EC 1.1.1.14) (Polyol dehydrogenase) (Ribitol dehydrogenase) (RDH) (EC 1.1.1.56) (Xylitol dehydrogenase) (XDH) (EC 1.1.1.9) | Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols. Is mostly active with D-sorbitol (D-glucitol), L-threitol, xylitol and ribitol as substrates, leading to the C2-oxidized products D-fructose, L-erythrulose, D-xylulose, and D-ribulose, respectively (PubMed:3365415). Is a key enzyme in the polyol pathway that interconverts glucose and fructose via sorbitol, which constitutes an important alternate route for glucose metabolism. The polyol pathway is believed to be involved in the etiology of diabetic complications, such as diabetic neuropathy and retinopathy, induced by hyperglycemia (PubMed:12962626, PubMed:25105142, PubMed:29966615). May play a role in sperm motility by using sorbitol as an alternative energy source for sperm motility (PubMed:16278369). May have a more general function in the metabolism of secondary alcohols since it also catalyzes the stereospecific oxidation of (2R,3R)-2,3-butanediol. To a lesser extent, can also oxidize L-arabinitol, galactitol and D-mannitol and glycerol in vitro. Oxidizes neither ethanol nor other primary alcohols. Cannot use NADP(+) as the electron acceptor (PubMed:3365415). {ECO:0000269|PubMed:16278369, ECO:0000269|PubMed:3365415, ECO:0000303|PubMed:25105142, ECO:0000303|PubMed:29966615, ECO:0000305|PubMed:12962626}. |
| Q9UPU5 | USP24 | T2570 | Sugiyama | 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}. |
| Q9BQ69 | MACROD1 | T196 | Sugiyama | ADP-ribose glycohydrolase MACROD1 (MACRO domain-containing protein 1) (O-acetyl-ADP-ribose deacetylase MACROD1) (EC 3.1.1.106) (Protein LRP16) ([Protein ADP-ribosylaspartate] hydrolase MACROD1) (EC 3.2.2.-) ([Protein ADP-ribosylglutamate] hydrolase MACROD1) (EC 3.2.2.-) | Removes ADP-ribose from aspartate and glutamate residues in proteins bearing a single ADP-ribose moiety (PubMed:23474712, PubMed:23474714). Inactive towards proteins bearing poly-ADP-ribose (PubMed:23474712, PubMed:23474714). Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins (PubMed:21257746). Plays a role in estrogen signaling (PubMed:17893710, PubMed:17914104, PubMed:19403568). Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen (PubMed:19022849). May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation (PubMed:17893710, PubMed:17914104). Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction (PubMed:17914104). Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells (PubMed:17893710). Enhances ESR1-mediated transcription activity (PubMed:17914104). {ECO:0000269|PubMed:17893710, ECO:0000269|PubMed:17914104, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19403568, ECO:0000269|PubMed:21257746, ECO:0000269|PubMed:23474712, ECO:0000269|PubMed:23474714}. |
| Q12765 | SCRN1 | T295 | Sugiyama | Secernin-1 | Regulates exocytosis in mast cells. Increases both the extent of secretion and the sensitivity of mast cells to stimulation with calcium (By similarity). {ECO:0000250}. |
| Q96QR8 | PURB | T31 | Sugiyama | Transcriptional regulator protein Pur-beta (Purine-rich element-binding protein B) | Transcriptional regulator which can act as an activator or a repressor. Represses the transcription of ACTA2 in fibroblasts and smooth muscle cells via its ability to interact with the purine-rich strand of a MCAT- containing element in the 5' flanking region of the gene. Represses the transcription of MYOCD, capable of repressing all isoforms of MYOCD but the magnitude of the repressive effects is most notable for the SMC- specific isoforms. Promotes hepatic glucose production by activating the transcription of ADCY6, leading to cAMP accumulation, increased PKA activity, CREB activation, and increased transcription of PCK1 and G6PC genes (By similarity). Has capacity to bind repeated elements in single-stranded DNA such as the purine-rich single strand of the PUR element located upstream of the MYC gene (PubMed:1448097). Participates in transcriptional and translational regulation of alpha-MHC expression in cardiac myocytes by binding to the purine-rich negative regulatory (PNR) element Modulates constitutive liver galectin-3 gene transcription by binding to its promoter. May play a role in the dendritic transport of a subset of mRNAs (By similarity). {ECO:0000250|UniProtKB:O35295, ECO:0000250|UniProtKB:Q68A21, ECO:0000269|PubMed:1448097}. |
| Q04637 | EIF4G1 | T1117 | Sugiyama | 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}. |
| Q9H4B4 | PLK3 | T82 | 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}. |
| O60927 | PPP1R11 | T88 | Sugiyama | E3 ubiquitin-protein ligase PPP1R11 (EC 2.3.2.27) (Hemochromatosis candidate gene V protein) (HCG V) (Protein phosphatase 1 regulatory subunit 11) (Protein phosphatase inhibitor 3) | Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 at 'Lys-754' leading to its degradation by the proteasome. Plays a role in regulating inflammatory cytokine release and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2 (PubMed:27805901). Inhibitor of protein phosphatase 1 (PubMed:9843442). {ECO:0000269|PubMed:27805901, ECO:0000269|PubMed:9843442}. |
| Q9UHD2 | TBK1 | T156 | 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}. |
| Q8IZ41 | RASEF | T689 | Sugiyama | Ras and EF-hand domain-containing protein (Ras-related protein Rab-45) | Binds predominantly GDP, and also GTP (PubMed:17448446). Acts as a dynein adapter protein that activates dynein-mediated transport and dynein-dynactin motility on microtubules (PubMed:30814157). {ECO:0000269|PubMed:17448446, ECO:0000269|PubMed:30814157}. |
| Q96PV0 | SYNGAP1 | T1077 | SIGNOR|iPTMNet | 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}. |
| Q99575 | POP1 | T103 | Sugiyama | 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}. |
| Q9Y3F4 | STRAP | T66 | Sugiyama | 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}. |
| A0A0B4J269 | None | T454 | ochoa | Melanocyte-stimulating hormone receptor (Melanocortin receptor 1) | Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Mediates melanogenesis, the production of eumelanin (black/brown) and phaeomelanin (red/yellow), via regulation of cAMP signaling in melanocytes. {ECO:0000256|ARBA:ARBA00023428}. |
| A0A1W2PQS6 | RPS10-NUDT3 | T118 | ochoa | Small ribosomal subunit protein eS10 (EC 3.6.1.52) (40S ribosomal protein S10) | Component of the 40S ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. {ECO:0000256|ARBA:ARBA00045797}. |
| A6NC98 | CCDC88B | T1366 | ochoa | Coiled-coil domain-containing protein 88B (Brain leucine zipper domain-containing protein) (Gipie) (Hook-related protein 3) (HkRP3) | Acts as a positive regulator of T-cell maturation and inflammatory function. Required for several functions of T-cells, in both the CD4(+) and the CD8(+) compartments and this includes expression of cell surface markers of activation, proliferation, and cytokine production in response to specific or non-specific stimulation (By similarity). Enhances NK cell cytotoxicity by positively regulating polarization of microtubule-organizing center (MTOC) to cytotoxic synapse, lytic granule transport along microtubules, and dynein-mediated clustering to MTOC (PubMed:25762780). Interacts with HSPA5 and stabilizes the interaction between HSPA5 and ERN1, leading to suppression of ERN1-induced JNK activation and endoplasmic reticulum stress-induced apoptosis (PubMed:21289099). {ECO:0000250|UniProtKB:Q4QRL3, ECO:0000269|PubMed:21289099, ECO:0000269|PubMed:25762780}. |
| A7KAX9 | ARHGAP32 | T1675 | ochoa | Rho GTPase-activating protein 32 (Brain-specific Rho GTPase-activating protein) (GAB-associated Cdc42/Rac GTPase-activating protein) (GC-GAP) (GTPase regulator interacting with TrkA) (Rho-type GTPase-activating protein 32) (Rho/Cdc42/Rac GTPase-activating protein RICS) (RhoGAP involved in the beta-catenin-N-cadherin and NMDA receptor signaling) (p200RhoGAP) (p250GAP) | GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:12446789, ECO:0000269|PubMed:12454018, ECO:0000269|PubMed:12531901, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:12819203, ECO:0000269|PubMed:12857875, ECO:0000269|PubMed:17663722}. |
| H0YJW9 | None | T58 | ochoa | Uncharacterized protein | None |
| J3KQ70 | INO80B-WBP1 | T87 | ochoa | HCG2039827, isoform CRA_e (INO80B-WBP1 readthrough (NMD candidate)) | None |
| M0QZ24 | None | T35 | ochoa | Glycosyl hydrolases family 38 C-terminal beta sandwich domain-containing protein | None |
| O00159 | MYO1C | T1038 | 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}. |
| O00401 | WASL | T221 | 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}. |
| O00754 | MAN2B1 | T848 | ochoa | Lysosomal alpha-mannosidase (Laman) (EC 3.2.1.24) (Lysosomal acid alpha-mannosidase) (Mannosidase alpha class 2B member 1) (Mannosidase alpha-B) [Cleaved into: Lysosomal alpha-mannosidase A peptide; Lysosomal alpha-mannosidase B peptide; Lysosomal alpha-mannosidase C peptide; Lysosomal alpha-mannosidase D peptide; Lysosomal alpha-mannosidase E peptide] | Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages. |
| O14497 | ARID1A | T294 | 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}. |
| O14639 | ABLIM1 | T670 | ochoa | Actin-binding LIM protein 1 (abLIM-1) (Actin-binding LIM protein family member 1) (Actin-binding double zinc finger protein) (LIMAB1) (Limatin) | May act as scaffold protein (By similarity). May play a role in the development of the retina. Has been suggested to play a role in axon guidance. {ECO:0000250, ECO:0000269|PubMed:9245787}. |
| O14818 | PSMA7 | T31 | 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}. |
| O14908 | GIPC1 | T238 | 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. |
| O14939 | PLD2 | T252 | psp | 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}. |
| O14965 | AURKA | T287 | 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}. |
| O14974 | PPP1R12A | T453 | 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}. |
| O15013 | ARHGEF10 | T88 | ochoa | Rho guanine nucleotide exchange factor 10 | May play a role in developmental myelination of peripheral nerves. {ECO:0000269|PubMed:14508709}. |
| O15014 | ZNF609 | T20 | 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}. |
| O15047 | SETD1A | T458 | 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 | T622 | 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 | T637 | 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 | T1371 | 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 | T676 | 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}. |
| O15173 | PGRMC2 | T93 | ochoa | Membrane-associated progesterone receptor component 2 (Progesterone membrane-binding protein) (Steroid receptor protein DG6) | Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan (By similarity). May serve as a universal non-classical progesterone receptor in the uterus (Probable). Intracellular heme chaperone required for delivery of labile, or signaling heme, to the nucleus (By similarity). Plays a role in adipocyte function and systemic glucose homeostasis (PubMed:28111073). In brown fat, which has a high demand for heme, delivery of labile heme in the nucleus regulates the activity of heme-responsive transcriptional repressors such as NR1D1 and BACH1 (By similarity). {ECO:0000250|UniProtKB:Q80UU9, ECO:0000269|PubMed:28111073, ECO:0000305|PubMed:28396637}. |
| O15264 | MAPK13 | T180 | ochoa|psp | 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}. |
| O15355 | PPM1G | T177 | 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 |
| O15355 | PPM1G | T196 | 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 |
| O15417 | TNRC18 | T2534 | ochoa | Trinucleotide repeat-containing gene 18 protein (Long CAG trinucleotide repeat-containing gene 79 protein) | None |
| O43166 | SIPA1L1 | T249 | 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}. |
| O43290 | SART1 | T22 | 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}. |
| O43293 | DAPK3 | T299 | psp | Death-associated protein kinase 3 (DAP kinase 3) (EC 2.7.11.1) (DAP-like kinase) (Dlk) (MYPT1 kinase) (Zipper-interacting protein kinase) (ZIP-kinase) | Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor. {ECO:0000269|PubMed:10356987, ECO:0000269|PubMed:11384979, ECO:0000269|PubMed:11781833, ECO:0000269|PubMed:12917339, ECO:0000269|PubMed:15096528, ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17126281, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:18995835, ECO:0000269|PubMed:21169990, ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:21487036, ECO:0000269|PubMed:23454120, ECO:0000269|PubMed:38009294}. |
| O43310 | CTIF | T240 | ochoa | CBP80/20-dependent translation initiation factor | Specifically required for the pioneer round of mRNA translation mediated by the cap-binding complex (CBC), that takes place during or right after mRNA export via the nuclear pore complex (NPC). Acts via its interaction with the NCBP1/CBP80 component of the CBC complex and recruits the 40S small subunit of the ribosome via eIF3. In contrast, it is not involved in steady state translation, that takes place when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. Also required for nonsense-mediated mRNA decay (NMD), the pioneer round of mRNA translation mediated by the cap-binding complex playing a central role in nonsense-mediated mRNA decay (NMD). {ECO:0000269|PubMed:19648179}. |
| O43379 | WDR62 | T1140 | 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}. |
| O43379 | WDR62 | T1148 | 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}. |
| O43491 | EPB41L2 | T812 | 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}. |
| O43598 | DNPH1 | T51 | 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}. |
| O43663 | PRC1 | T491 | 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}. |
| O43822 | CFAP410 | T170 | ochoa | Cilia- and flagella-associated protein 410 (C21orf-HUMF09G8.5) (Leucine-rich repeat-containing protein 76) (YF5/A2) | Plays a role in cilia formation and/or maintenance (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). Involved in DNA damage repair (PubMed:26290490). {ECO:0000250|UniProtKB:Q8C6G1, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:26290490}. |
| O43824 | GTPBP6 | T315 | ochoa | Putative GTP-binding protein 6 (Pseudoautosomal GTP-binding protein-like) | None |
| O43900 | PRICKLE3 | T414 | ochoa | Prickle planar cell polarity protein 3 (LIM domain only protein 6) (LMO-6) (Prickle-like protein 3) (Pk3) (Triple LIM domain protein 6) | Involved in the planar cell polarity (PCP) pathway that is essential for the polarization of epithelial cells during morphogenetic processes, including gastrulation and neurulation (By similarity). PCP is maintained by two molecular modules, the global and the core modules, PRICKLE3 being part of the core module (By similarity). Distinct complexes of the core module segregate to opposite sides of the cell, where they interact with the opposite complex in the neighboring cell at or near the adherents junctions (By similarity). Involved in the organization of the basal body (By similarity). Involved in cilia growth and positioning (By similarity). Required for proper assembly, stability, and function of mitochondrial membrane ATP synthase (mitochondrial complex V) (PubMed:32516135). {ECO:0000250|UniProtKB:A8WH69, ECO:0000269|PubMed:32516135}. |
| O60285 | NUAK1 | T414 | ochoa | NUAK family SNF1-like kinase 1 (EC 2.7.11.1) (AMPK-related protein kinase 5) (ARK5) (Omphalocele kinase 1) | Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171, ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}. |
| O60330 | PCDHGA12 | Y879 | ochoa | Protocadherin gamma-A12 (PCDH-gamma-A12) (Cadherin-21) (Fibroblast cadherin-3) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| O60356 | NUPR1 | T54 | ochoa | Nuclear protein 1 (Candidate of metastasis 1) (Protein p8) | Transcription regulator that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Thereby participates in the regulation of many processes namely cell-cycle, apoptosis, autophagy and DNA repair responses (PubMed:11056169, PubMed:11940591, PubMed:16300740, PubMed:16478804, PubMed:18690848, PubMed:19650074, PubMed:19723804, PubMed:20181828, PubMed:22565310, PubMed:22858377, PubMed:30451898). Controls cell cycle progression and protects cells from genotoxic stress induced by doxorubicin through the complex formation with TP53 and EP300 that binds CDKN1A promoter leading to transcriptional induction of CDKN1A (PubMed:18690848). Protects pancreatic cancer cells from stress-induced cell death by binding the RELB promoter and activating its transcription, leading to IER3 transactivation (PubMed:22565310). Negatively regulates apoptosis through interaction with PTMA (PubMed:16478804). Inhibits autophagy-induced apoptosis in cardiac cells through FOXO3 interaction, inducing cytoplasmic translocation of FOXO3 thereby preventing the FOXO3 association with the pro-autophagic BNIP3 promoter (PubMed:20181828). Inhibits cell growth and facilitates programmed cell death by apoptosis after adriamycin-induced DNA damage through transactivation of TP53 (By similarity). Regulates methamphetamine-induced apoptosis and autophagy through DDIT3-mediated endoplasmic reticulum stress pathway (By similarity). Participates in DNA repair following gamma-irradiation by facilitating DNA access of the transcription machinery through interaction with MSL1 leading to inhibition of histone H4' Lys-16' acetylation (H4K16ac) (PubMed:19650074). Coactivator of PAX2 transcription factor activity, both by recruiting EP300 to increase PAX2 transcription factor activity and by binding PAXIP1 to suppress PAXIP1-induced inhibition on PAX2 (PubMed:11940591). Positively regulates cell cycle progression through interaction with COPS5 inducing cytoplasmic translocation of CDKN1B leading to the CDKN1B degradation (PubMed:16300740). Coordinates, through its interaction with EP300, the assiociation of MYOD1, EP300 and DDX5 to the MYOG promoter, leading to inhibition of cell-cycle progression and myogenic differentiation promotion (PubMed:19723804). Negatively regulates beta cell proliferation via inhibition of cell-cycle regulatory genes expression through the suppression of their promoter activities (By similarity). Also required for LHB expression and ovarian maturation (By similarity). Exacerbates CNS inflammation and demyelination upon cuprizone treatment (By similarity). {ECO:0000250|UniProtKB:O54842, ECO:0000250|UniProtKB:Q9WTK0, ECO:0000269|PubMed:11056169, ECO:0000269|PubMed:11940591, ECO:0000269|PubMed:16300740, ECO:0000269|PubMed:16478804, ECO:0000269|PubMed:18690848, ECO:0000269|PubMed:19650074, ECO:0000269|PubMed:19723804, ECO:0000269|PubMed:20181828, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:22858377, ECO:0000269|PubMed:30451898}. |
| O60674 | JAK2 | T174 | psp | Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2) | Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}. |
| O60716 | CTNND1 | T199 | 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}. |
| O60779 | SLC19A2 | T239 | ochoa | Thiamine transporter 1 (ThTr-1) (ThTr1) (Solute carrier family 19 member 2) (Thiamine carrier 1) (TC1) | High-affinity transporter for the intake of thiamine (PubMed:10391222, PubMed:10542220, PubMed:21836059, PubMed:33008889, PubMed:35512554, PubMed:35724964). Mediates H(+)-dependent pyridoxine transport (PubMed:33008889, PubMed:35512554, PubMed:35724964). {ECO:0000269|PubMed:10391222, ECO:0000269|PubMed:10542220, ECO:0000269|PubMed:21836059, ECO:0000269|PubMed:33008889, ECO:0000269|PubMed:35512554, ECO:0000269|PubMed:35724964}. |
| O60784 | TOM1 | T406 | ochoa | Target of Myb1 membrane trafficking protein (Target of Myb protein 1) | Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways (PubMed:14563850, PubMed:15047686, PubMed:23023224, PubMed:25588840, PubMed:26320582, PubMed:31371777). Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (PubMed:23023224). Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (PubMed:23023224). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (PubMed:31371777). Binds to polyubiquitinated proteins via its GAT domain (PubMed:14563850). In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686). The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (PubMed:14563850, PubMed:15047686). Mediates clathrin recruitment to early endosomes by ZFYVE16 (PubMed:15657082). Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns(3)P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking (PubMed:26320582). Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation (PubMed:25588840). PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation (PubMed:25588840). Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (PubMed:15047686, PubMed:26320582). {ECO:0000269|PubMed:14563850, ECO:0000269|PubMed:15047686, ECO:0000269|PubMed:15657082, ECO:0000269|PubMed:23023224, ECO:0000269|PubMed:25588840, ECO:0000269|PubMed:26320582, ECO:0000269|PubMed:31371777}. |
| O60828 | PQBP1 | T234 | ochoa | Polyglutamine-binding protein 1 (PQBP-1) (38 kDa nuclear protein containing a WW domain) (Npw38) (Polyglutamine tract-binding protein 1) | Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development (PubMed:10198427, PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:10332029, PubMed:12062018, PubMed:20410308, PubMed:23512658). May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery (PubMed:10198427). May be involved in ATXN1 mutant-induced cell death (PubMed:12062018). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (PubMed:12062018). Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules (PubMed:21933836). Also acts as an innate immune sensor of infection by retroviruses, such as HIV, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:26046437). Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production (PubMed:26046437). {ECO:0000269|PubMed:10198427, ECO:0000269|PubMed:10332029, ECO:0000269|PubMed:12062018, ECO:0000269|PubMed:20410308, ECO:0000269|PubMed:21933836, ECO:0000269|PubMed:23512658, ECO:0000269|PubMed:26046437}. |
| O60861 | GAS7 | T153 | ochoa | Growth arrest-specific protein 7 (GAS-7) | May play a role in promoting maturation and morphological differentiation of cerebellar neurons. |
| O75052 | NOS1AP | T210 | 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}. |
| O75369 | FLNB | T980 | 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 | T2017 | 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 | T2110 | 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. |
| O75427 | LRCH4 | T318 | 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 | T36 | 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 | T56 | 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 | T61 | 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 | T442 | 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}. |
| O75791 | GRAP2 | T246 | 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. |
| O75937 | DNAJC8 | T22 | ochoa | DnaJ homolog subfamily C member 8 (Splicing protein spf31) | Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells (PubMed:27133716). {ECO:0000269|PubMed:27133716}. |
| O75943 | RAD17 | T633 | psp | Cell cycle checkpoint protein RAD17 (hRad17) (RF-C/activator 1 homolog) | Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). Has a weak ATPase activity required for binding to chromatin (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). Participates in the recruitment of the 9-1-1 (RAD1-RAD9-HUS1) complex and RHNO1 onto chromatin, and in CHEK1 activation (PubMed:21659603). Involved in homologous recombination by mediating recruitment of the MRN complex to DNA damage sites (PubMed:24534091). May also serve as a sensor of DNA replication progression (PubMed:12578958, PubMed:14500819, PubMed:15538388). {ECO:0000269|PubMed:10208430, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:12578958, ECO:0000269|PubMed:12672690, ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:14624239, ECO:0000269|PubMed:15235112, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:24534091}. |
| O76061 | STC2 | T254 | ochoa | Stanniocalcin-2 (STC-2) (Stanniocalcin-related protein) (STC-related protein) (STCRP) | Has an anti-hypocalcemic action on calcium and phosphate homeostasis. |
| O76094 | SRP72 | T602 | 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}. |
| O76094 | SRP72 | T618 | 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 | T805 | 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}. |
| O94818 | NOL4 | T295 | ochoa | Nucleolar protein 4 (Nucleolar-localized protein) | None |
| O94822 | LTN1 | T575 | ochoa | E3 ubiquitin-protein ligase listerin (EC 2.3.2.27) (RING finger protein 160) (RING-type E3 ubiquitin transferase listerin) (Zinc finger protein 294) | E3 ubiquitin-protein ligase component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:23685075, PubMed:25132172, PubMed:25578875, PubMed:28757607). Within the RQC complex, LTN1 is recruited to stalled 60S ribosomal subunits by NEMF and mediates ubiquitination of stalled nascent chains (PubMed:25578875). Ubiquitination leads to VCP/p97 recruitment for extraction and degradation of the incomplete translation product (By similarity). {ECO:0000250|UniProtKB:Q04781, ECO:0000269|PubMed:23685075, ECO:0000269|PubMed:25132172, ECO:0000269|PubMed:25578875, ECO:0000269|PubMed:28757607}. |
| O94915 | FRYL | T1915 | 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}. |
| O94953 | KDM4B | T1069 | ochoa | Lysine-specific demethylase 4B (EC 1.14.11.66) (JmjC domain-containing histone demethylation protein 3B) (Jumonji domain-containing protein 2B) ([histone H3]-trimethyl-L-lysine(9) demethylase 4B) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate (PubMed:16603238, PubMed:28262558). Plays a critical role in the development of the central nervous system (CNS). {ECO:0000250|UniProtKB:Q91VY5, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}. |
| O95294 | RASAL1 | T334 | ochoa | RasGAP-activating-like protein 1 (RAS protein activator like 1) (Ras GTPase-activating-like protein) | Probable inhibitory regulator of the Ras-cyclic AMP pathway (PubMed:9751798). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:9751798}. |
| P00488 | F13A1 | T689 | ochoa | Coagulation factor XIII A chain (Coagulation factor XIIIa) (EC 2.3.2.13) (Protein-glutamine gamma-glutamyltransferase A chain) (Transglutaminase A chain) | Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. {ECO:0000269|PubMed:27363989}. |
| P00558 | PGK1 | T168 | 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}. |
| P00558 | PGK1 | T329 | 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}. |
| P00558 | PGK1 | T385 | 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}. |
| P02489 | CRYAA | T148 | psp | Alpha-crystallin A chain (Heat shock protein beta-4) (HspB4) (Heat shock protein family B member 4) [Cleaved into: Alpha-crystallin A(1-172); Alpha-crystallin A(1-168); Alpha-crystallin A(1-162)] | Contributes to the transparency and refractive index of the lens (PubMed:18302245). In its oxidized form (absence of intramolecular disulfide bond), acts as a chaperone, preventing aggregation of various proteins under a wide range of stress conditions (PubMed:18199971, PubMed:19595763, PubMed:22120592, PubMed:31792453). Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373). {ECO:0000269|PubMed:18199971, ECO:0000269|PubMed:19595763, ECO:0000269|PubMed:22120592, ECO:0000269|PubMed:28935373, ECO:0000269|PubMed:31792453, ECO:0000303|PubMed:18302245}. |
| P02545 | LMNA | T534 | 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 | T643 | 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}. |
| P02649 | APOE | T148 | ochoa | Apolipoprotein E (Apo-E) | APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754908, PubMed:1911868, PubMed:6860692). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:14754908, PubMed:1911868, PubMed:1917954, PubMed:23620513, PubMed:2762297, PubMed:6860692, PubMed:9395455). Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:2762297, PubMed:6860692, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:1911868, PubMed:6860692). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:12950167, PubMed:1530612, PubMed:1917954, PubMed:20030366, PubMed:20303980, PubMed:2063194, PubMed:2762297, PubMed:7635945, PubMed:7768901, PubMed:8756331, PubMed:8939961). Finally, APOE also has a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:23676495, PubMed:7635945, PubMed:9395455, PubMed:9488694). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:23676495, PubMed:29516132, PubMed:9395455). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:1917954, PubMed:2762297, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:14754908, PubMed:23620513, PubMed:9395455). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:25173806, PubMed:8939961). APOE is also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). Binds to the immune cell receptor LILRB4 (PubMed:30333625). APOE may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074). {ECO:0000250|UniProtKB:P08226, ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:1530612, ECO:0000269|PubMed:1911868, ECO:0000269|PubMed:1917954, ECO:0000269|PubMed:20030366, ECO:0000269|PubMed:20303980, ECO:0000269|PubMed:2063194, ECO:0000269|PubMed:23620513, ECO:0000269|PubMed:23676495, ECO:0000269|PubMed:2762297, ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:30333625, ECO:0000269|PubMed:6860692, ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7768901, ECO:0000269|PubMed:8756331, ECO:0000269|PubMed:8939961, ECO:0000269|PubMed:9395455, ECO:0000269|PubMed:9488694, ECO:0000303|PubMed:25173806, ECO:0000303|PubMed:29516132}.; FUNCTION: (Microbial infection) Through its interaction with HCV envelope glycoprotein E2, participates in the attachment of HCV to HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface and to the assembly, maturation and infectivity of HCV viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434). {ECO:0000269|PubMed:25122793, ECO:0000269|PubMed:29695434}. |
| P02671 | FGA | T357 | 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}. |
| P02686 | MBP | T169 | 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}. |
| P04083 | ANXA1 | T227 | ochoa | Annexin A1 (Annexin I) (Annexin-1) (Calpactin II) (Calpactin-2) (Chromobindin-9) (Lipocortin I) (Phospholipase A2 inhibitory protein) (p35) [Cleaved into: Annexin Ac2-26] | Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.; FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:25664854}. |
| P04406 | GAPDH | T75 | ochoa|psp | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment 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 (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04406 | GAPDH | T99 | psp | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment 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 (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04406 | GAPDH | T211 | ochoa | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment 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 (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04406 | GAPDH | T229 | ochoa|psp | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment 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 (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04626 | ERBB2 | T875 | 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}. |
| P05062 | ALDOB | T39 | ochoa | Fructose-bisphosphate aldolase B (EC 4.1.2.13) (Liver-type aldolase) | Catalyzes the aldol cleavage of fructose 1,6-biphosphate to form two triosephosphates dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in glycolysis as well as the reverse stereospecific aldol addition reaction in gluconeogenesis. In fructolysis, metabolizes fructose 1-phosphate derived from the phosphorylation of dietary fructose by fructokinase into dihydroxyacetone phosphate and D-glyceraldehyde (PubMed:10970798, PubMed:12205126, PubMed:20848650). Acts as an adapter independently of its enzymatic activity, exerts a tumor suppressor role by stabilizing the ternary complex with G6PD and TP53 to inhibit G6PD activity and keep oxidative pentose phosphate metabolism in check (PubMed:35122041). {ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:20848650, ECO:0000269|PubMed:35122041}. |
| P05423 | POLR3D | T21 | ochoa | DNA-directed RNA polymerase III subunit RPC4 (RNA polymerase III subunit C4) (DNA-directed RNA polymerase III subunit D) (Protein BN51) (RNA polymerase III 47 kDa subunit) (RPC53 homolog) | DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:12391170, PubMed:20413673, PubMed:33558764, PubMed:34675218, PubMed:35637192). Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Assembles with POLR3E/RPC5 forming a subcomplex that binds the Pol III core. Enables recruitment of Pol III at transcription initiation site and drives transcription initiation from both type 2 and type 3 DNA promoters. Required for efficient transcription termination and reinitiation (By similarity) (PubMed:12391170, PubMed:20413673, PubMed:35637192). Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway (PubMed:19609254, PubMed:19631370). {ECO:0000250|UniProtKB:P25441, ECO:0000269|PubMed:12391170, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20413673, ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:34675218, ECO:0000269|PubMed:35637192}. |
| P05455 | SSB | T362 | 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}. |
| P05783 | KRT18 | T404 | ochoa | Keratin, type I cytoskeletal 18 (Cell proliferation-inducing gene 46 protein) (Cytokeratin-18) (CK-18) (Keratin-18) (K18) | Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection. {ECO:0000250, ECO:0000269|PubMed:15529338, ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:7523419, ECO:0000269|PubMed:8522591, ECO:0000269|PubMed:9298992, ECO:0000269|PubMed:9524113}. |
| P06239 | LCK | T159 | 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 | T213 | 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}. |
| P06733 | ENO1 | T41 | 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 | T376 | 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 | T379 | 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 | T390 | 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}. |
| P07205 | PGK2 | T385 | ochoa | Phosphoglycerate kinase 2 (EC 2.7.2.3) (Phosphoglycerate kinase, testis specific) | Essential for sperm motility and male fertility (PubMed:26677959). Not required for the completion of spermatogenesis (By similarity). {ECO:0000250|UniProtKB:P09041, ECO:0000269|PubMed:26677959}. |
| P07437 | TUBB | T107 | 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. |
| P08047 | SP1 | T43 | 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}. |
| P08047 | SP1 | T737 | 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}. |
| P08758 | ANXA5 | T200 | ochoa | Annexin A5 (Anchorin CII) (Annexin V) (Annexin-5) (Calphobindin I) (CPB-I) (Endonexin II) (Lipocortin V) (Placental anticoagulant protein 4) (PP4) (Placental anticoagulant protein I) (PAP-I) (Thromboplastin inhibitor) (Vascular anticoagulant-alpha) (VAC-alpha) | This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. |
| P09104 | ENO2 | T41 | ochoa | Gamma-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 2) (Neural enolase) (Neuron-specific enolase) (NSE) | Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). {ECO:0000250}. |
| P09104 | ENO2 | T376 | ochoa | Gamma-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 2) (Neural enolase) (Neuron-specific enolase) (NSE) | Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). {ECO:0000250}. |
| P09104 | ENO2 | T379 | ochoa | Gamma-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 2) (Neural enolase) (Neuron-specific enolase) (NSE) | Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). {ECO:0000250}. |
| P09104 | ENO2 | T390 | ochoa | Gamma-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 2) (Neural enolase) (Neuron-specific enolase) (NSE) | Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). {ECO:0000250}. |
| P0DPH7 | TUBA3C | T56 | 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 | T56 | 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. |
| P10636 | MAPT | T71 | 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}. |
| P10909 | CLU | T388 | ochoa | Clusterin (Aging-associated gene 4 protein) (Apolipoprotein J) (Apo-J) (Complement cytolysis inhibitor) (CLI) (Complement-associated protein SP-40,40) (Ku70-binding protein 1) (NA1/NA2) (Sulfated glycoprotein 2) (SGP-2) (Testosterone-repressed prostate message 2) (TRPM-2) [Cleaved into: Clusterin beta chain (ApoJalpha) (Complement cytolysis inhibitor a chain) (SP-40,40 beta-chain); Clusterin alpha chain (ApoJbeta) (Complement cytolysis inhibitor b chain) (SP-40,40 alpha-chain)] | [Isoform 1]: Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17407782, PubMed:17412999). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement: inhibits assembly of the complement membrane attack complex (MAC) by preventing polymerization of C9 pore component of the MAC complex (PubMed:2780565, PubMed:1903064, PubMed:2601725, PubMed:2721499, PubMed:1551440, PubMed:9200695, PubMed:34667172). Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity). {ECO:0000250|UniProtKB:P05371, ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:1551440, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:1903064, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2601725, ECO:0000269|PubMed:2721499, ECO:0000269|PubMed:2780565, ECO:0000269|PubMed:34667172, ECO:0000269|PubMed:9200695}.; FUNCTION: [Isoform 6]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. {ECO:0000269|PubMed:24073260}.; FUNCTION: [Isoform 4]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Promotes cell death through interaction with BCL2L1 that releases and activates BAX (PubMed:21567405). {ECO:0000269|PubMed:21567405, ECO:0000269|PubMed:24073260}. |
| P11137 | MAP2 | T733 | 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. |
| P11142 | HSPA8 | T177 | 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}. |
| P11274 | BCR | T302 | 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}. |
| P11277 | SPTB | T2110 | ochoa|psp | Spectrin beta chain, erythrocytic (Beta-I spectrin) | Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane. |
| P12270 | TPR | T2042 | 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}. |
| P12882 | MYH1 | T650 | ochoa | Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) | Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}. |
| P12883 | MYH7 | T646 | 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}. |
| P13164 | IFITM1 | T73 | ochoa | Interferon-induced transmembrane protein 1 (Dispanin subfamily A member 2a) (DSPA2a) (Interferon-induced protein 17) (Interferon-inducible protein 9-27) (Leu-13 antigen) (CD antigen CD225) | IFN-induced antiviral protein which inhibits the entry of viruses to the host cell cytoplasm, permitting endocytosis, but preventing subsequent viral fusion and release of viral contents into the cytosol. Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) (PubMed:26354436, PubMed:33270927). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry and SARS-CoV and SARS-CoV-2 S protein-mediated viral entry. Also implicated in cell adhesion and control of cell growth and migration (PubMed:33270927). Inhibits SARS-CoV-2 S protein-mediated syncytia formation (PubMed:33051876). Plays a key role in the antiproliferative action of IFN-gamma either by inhibiting the ERK activation or by arresting cell growth in G1 phase in a p53-dependent manner. Acts as a positive regulator of osteoblast differentiation. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation (PubMed:26354436). IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome (PubMed:26354436). {ECO:0000269|PubMed:16847454, ECO:0000269|PubMed:20064371, ECO:0000269|PubMed:20838853, ECO:0000269|PubMed:21177806, ECO:0000269|PubMed:21253575, ECO:0000269|PubMed:21976647, ECO:0000269|PubMed:22479637, ECO:0000269|PubMed:22634173, ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:33270927}. |
| P13533 | MYH6 | T648 | ochoa | Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) | Muscle contraction. |
| P13535 | MYH8 | T649 | ochoa | Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) | Muscle contraction. |
| P13798 | APEH | T51 | ochoa | Acylamino-acid-releasing enzyme (AARE) (EC 3.4.19.1) (Acyl-peptide hydrolase) (APH) (Acylaminoacyl-peptidase) (Oxidized protein hydrolase) (OPH) | This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus (PubMed:10719179, PubMed:1740429, PubMed:2006156). It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Also, involved in the degradation of oxidized and glycated proteins (PubMed:10719179). {ECO:0000250|UniProtKB:P13676, ECO:0000269|PubMed:10719179, ECO:0000269|PubMed:1740429, ECO:0000269|PubMed:2006156}. |
| P13929 | ENO3 | T41 | 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}. |
| P13929 | ENO3 | T376 | 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}. |
| P13929 | ENO3 | T379 | 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}. |
| P13929 | ENO3 | T390 | 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 | T80 | 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 | T328 | 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}. |
| P14625 | HSP90B1 | T669 | psp | 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}. |
| P14784 | IL2RB | T533 | ochoa | Interleukin-2 receptor subunit beta (IL-2 receptor subunit beta) (IL-2R subunit beta) (IL-2RB) (High affinity IL-2 receptor subunit beta) (Interleukin-15 receptor subunit beta) (p70-75) (p75) (CD antigen CD122) | Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770, PubMed:31040185). {ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:31040184, ECO:0000269|PubMed:31040185}. |
| P15056 | BRAF | T470 | 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}. |
| P15121 | AKR1B1 | T29 | ochoa | Aldo-keto reductase family 1 member B1 (EC 1.1.1.21) (EC 1.1.1.300) (EC 1.1.1.372) (EC 1.1.1.54) (Aldehyde reductase) (Aldose reductase) (AR) | Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia (PubMed:1936586). Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:19010934, PubMed:8343525). Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:21329684). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:17381426, ECO:0000269|PubMed:19010934, ECO:0000269|PubMed:1936586, ECO:0000269|PubMed:21329684, ECO:0000269|PubMed:8343525}. |
| P15924 | DSP | T184 | 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}. |
| P16150 | SPN | T341 | 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 | T343 | 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}. |
| P16615 | ATP2A2 | T653 | 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}. |
| P16885 | PLCG2 | T1045 | psp | 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 | T67 | 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}. |
| P17661 | DES | T76 | psp | 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}. |
| P17661 | DES | T77 | psp | 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}. |
| P18031 | PTPN1 | T368 | 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}. |
| P18583 | SON | T37 | 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}. |
| P18825 | ADRA2C | T334 | ochoa | Alpha-2C adrenergic receptor (Alpha-2 adrenergic receptor subtype C4) (Alpha-2C adrenoreceptor) (Alpha-2C adrenoceptor) (Alpha-2CAR) | Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. |
| P18887 | XRCC1 | T358 | 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}. |
| P19525 | EIF2AK2 | T446 | 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}. |
| P21127 | CDK11B | T448 | ochoa | Cyclin-dependent kinase 11B (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 1) (CLK-1) (Cell division protein kinase 11B) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L1) (p58 CLK-1) | Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:18216018, ECO:0000269|PubMed:2217177}. |
| P21291 | CSRP1 | T82 | ochoa | Cysteine and glycine-rich protein 1 (Cysteine-rich protein 1) (CRP) (CRP1) (Epididymis luminal protein 141) (HEL-141) | Could play a role in neuronal development. |
| P21291 | CSRP1 | T101 | ochoa | Cysteine and glycine-rich protein 1 (Cysteine-rich protein 1) (CRP) (CRP1) (Epididymis luminal protein 141) (HEL-141) | Could play a role in neuronal development. |
| P21333 | FLNA | T572 | 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 | T1089 | 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 | T1739 | 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 | T2062 | 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 | T2229 | 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 | T55 | 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}. |
| P22735 | TGM1 | T104 | 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 | T195 | 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 | T87 | 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}. |
| P24534 | EEF1B2 | T88 | 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}. |
| P25100 | ADRA1D | T328 | psp | Alpha-1D adrenergic receptor (Alpha-1A adrenergic receptor) (Alpha-1D adrenoreceptor) (Alpha-1D adrenoceptor) (Alpha-adrenergic receptor 1a) | This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium. |
| P25205 | MCM3 | T383 | psp | 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}. |
| P26641 | EEF1G | T43 | ochoa | Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) | Probably plays a role in anchoring the complex to other cellular components. |
| P27361 | MAPK3 | T198 | ochoa|psp | Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}. |
| P28482 | MAPK1 | T181 | ochoa|psp | Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}. |
| P29144 | TPP2 | T45 | ochoa | Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) | Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}. |
| P29317 | EPHA2 | T771 | 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}. |
| P29475 | NOS1 | T109 | ochoa | Nitric oxide synthase 1 (EC 1.14.13.39) (Constitutive NOS) (NC-NOS) (NOS type I) (Neuronal NOS) (N-NOS) (nNOS) (Nitric oxide synthase, brain) (bNOS) (Peptidyl-cysteine S-nitrosylase NOS1) | Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. {ECO:0000269|PubMed:35772285}. |
| P29972 | AQP1 | T157 | psp | Aquaporin-1 (AQP-1) (Aquaporin-CHIP) (Channel-like integral membrane protein of 28 kDa) (Urine water channel) | Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues (PubMed:1373524, PubMed:23219802). Could also be permeable to small solutes including hydrogen peroxide, glycerol and gases such as amonnia (NH3), nitric oxide (NO) and carbon dioxide (CO2) (PubMed:16682607, PubMed:17012249, PubMed:19273840, PubMed:33028705, PubMed:8584435). Recruited to the ankyrin-1 complex, a multiprotein complex of the erythrocyte membrane, it could be part of a CO2 metabolon, linking facilitated diffusion of CO2 across the membrane, anion exchange of Cl(-)/HCO3(-) and interconversion of dissolved CO2 and carbonic acid in the cytosol (PubMed:17012249, PubMed:35835865). In vitro, it shows non-selective gated cation channel activity and may be permeable to cations like K(+) and Na(+) in vivo (PubMed:36949749, PubMed:8703053). {ECO:0000269|PubMed:1373524, ECO:0000269|PubMed:16682607, ECO:0000269|PubMed:17012249, ECO:0000269|PubMed:19273840, ECO:0000269|PubMed:23219802, ECO:0000269|PubMed:33028705, ECO:0000269|PubMed:35835865, ECO:0000269|PubMed:36949749, ECO:0000269|PubMed:8584435, ECO:0000269|PubMed:8703053}. |
| P30405 | PPIF | T161 | ochoa | 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}. |
| P30622 | CLIP1 | T351 | 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}. |
| P31942 | HNRNPH3 | T57 | ochoa | Heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3) (Heterogeneous nuclear ribonucleoprotein 2H9) (hnRNP 2H9) | Involved in the splicing process and participates in early heat shock-induced splicing arrest. Due to their great structural variations the different isoforms may possess different functions in the splicing reaction. |
| P31942 | HNRNPH3 | T207 | ochoa | Heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3) (Heterogeneous nuclear ribonucleoprotein 2H9) (hnRNP 2H9) | Involved in the splicing process and participates in early heat shock-induced splicing arrest. Due to their great structural variations the different isoforms may possess different functions in the splicing reaction. |
| P32119 | PRDX2 | T142 | ochoa | Peroxiredoxin-2 (EC 1.11.1.24) (Natural killer cell-enhancing factor B) (NKEF-B) (PRP) (Thiol-specific antioxidant protein) (TSA) (Thioredoxin peroxidase 1) (Thioredoxin-dependent peroxide reductase 1) (Thioredoxin-dependent peroxiredoxin 2) | 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). {ECO:0000269|PubMed:9497357}. |
| P32926 | DSG3 | T768 | ochoa | Desmoglein-3 (130 kDa pemphigus vulgaris antigen) (PVA) (Cadherin family member 6) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:31835537). Required for adherens and desmosome junction assembly in response to mechanical force in keratinocytes (PubMed:31835537). Required for desmosome-mediated cell-cell adhesion of cells surrounding the telogen hair club and the basal layer of the outer root sheath epithelium, consequently is essential for the anchoring of telogen hairs in the hair follicle (PubMed:9701552). Required for the maintenance of the epithelial barrier via promoting desmosome-mediated intercellular attachment of suprabasal epithelium to basal cells (By similarity). May play a role in the protein stability of the desmosome plaque components DSP, JUP, PKP1, PKP2 and PKP3 (PubMed:22294297). Required for YAP1 localization at the plasma membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, PKP1 and YWHAG (PubMed:31835537). May also be involved in the positive regulation of YAP1 target gene transcription and as a result cell proliferation (PubMed:31835537). Positively regulates cellular contractility and cell junction formation via organization of cortical F-actin bundles and anchoring of actin to tight junctions, in conjunction with RAC1 (PubMed:22796473). The cytoplasmic pool of DSG3 is required for the localization of CDH1 and CTNNB1 at developing adherens junctions, potentially via modulation of SRC activity (PubMed:22294297). Inhibits keratinocyte migration via suppression of p38MAPK signaling, may therefore play a role in moderating wound healing (PubMed:26763450). {ECO:0000250|UniProtKB:O35902, ECO:0000269|PubMed:22294297, ECO:0000269|PubMed:22796473, ECO:0000269|PubMed:26763450, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9701552}. |
| P32926 | DSG3 | T772 | ochoa | Desmoglein-3 (130 kDa pemphigus vulgaris antigen) (PVA) (Cadherin family member 6) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:31835537). Required for adherens and desmosome junction assembly in response to mechanical force in keratinocytes (PubMed:31835537). Required for desmosome-mediated cell-cell adhesion of cells surrounding the telogen hair club and the basal layer of the outer root sheath epithelium, consequently is essential for the anchoring of telogen hairs in the hair follicle (PubMed:9701552). Required for the maintenance of the epithelial barrier via promoting desmosome-mediated intercellular attachment of suprabasal epithelium to basal cells (By similarity). May play a role in the protein stability of the desmosome plaque components DSP, JUP, PKP1, PKP2 and PKP3 (PubMed:22294297). Required for YAP1 localization at the plasma membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, PKP1 and YWHAG (PubMed:31835537). May also be involved in the positive regulation of YAP1 target gene transcription and as a result cell proliferation (PubMed:31835537). Positively regulates cellular contractility and cell junction formation via organization of cortical F-actin bundles and anchoring of actin to tight junctions, in conjunction with RAC1 (PubMed:22796473). The cytoplasmic pool of DSG3 is required for the localization of CDH1 and CTNNB1 at developing adherens junctions, potentially via modulation of SRC activity (PubMed:22294297). Inhibits keratinocyte migration via suppression of p38MAPK signaling, may therefore play a role in moderating wound healing (PubMed:26763450). {ECO:0000250|UniProtKB:O35902, ECO:0000269|PubMed:22294297, ECO:0000269|PubMed:22796473, ECO:0000269|PubMed:26763450, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9701552}. |
| P33240 | CSTF2 | T507 | 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}. |
| P34972 | CNR2 | T340 | ochoa|psp | Cannabinoid receptor 2 (CB-2) (CB2) (hCB2) (CX5) | Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis. {ECO:0000269|PubMed:10051546, ECO:0000269|PubMed:12663043, ECO:0000269|PubMed:12711605, ECO:0000269|PubMed:18692962}. |
| P35222 | CTNNB1 | T472 | psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35408 | PTGER4 | T225 | ochoa | 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. |
| P35568 | IRS1 | T498 | ochoa | 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}. |
| P36896 | ACVR1B | T206 | psp | Activin receptor type-1B (EC 2.7.11.30) (Activin receptor type IB) (ACTR-IB) (Activin receptor-like kinase 4) (ALK-4) (Serine/threonine-protein kinase receptor R2) (SKR2) | Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, ECO:0000269|PubMed:9892009}. |
| P36897 | TGFBR1 | T204 | 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}. |
| P37802 | TAGLN2 | T180 | ochoa | Transgelin-2 (Epididymis tissue protein Li 7e) (SM22-alpha homolog) | None |
| P37840 | SNCA | T64 | 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}. |
| P38646 | HSPA9 | T398 | ochoa | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| P38936 | CDKN1A | T80 | 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}. |
| P40189 | IL6ST | T890 | psp | 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}. |
| P40200 | CD96 | T508 | ochoa | T-cell surface protein tactile (Cell surface antigen CD96) (T cell-activated increased late expression protein) (CD antigen CD96) | May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation. |
| P40259 | CD79B | T206 | ochoa | B-cell antigen receptor complex-associated protein beta chain (B-cell-specific glycoprotein B29) (Ig-beta) (Immunoglobulin-associated B29 protein) (CD antigen CD79b) | Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation. {ECO:0000269|PubMed:12097390, ECO:0000269|PubMed:8617796, ECO:0000269|PubMed:9057631}. |
| P40818 | USP8 | T594 | 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 | T73 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P41091 | EIF2S3 | T21 | ochoa | 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}. |
| P41236 | PPP1R2 | T92 | ochoa | Protein phosphatase inhibitor 2 (IPP-2) | Inhibitor of protein-phosphatase 1. |
| P42166 | TMPO | T138 | 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 | T2471 | ochoa | 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}. |
| P45985 | MAP2K4 | T261 | psp | Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}. |
| P46013 | MKI67 | T856 | 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 | T1919 | 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 | T2402 | 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}. |
| P46531 | NOTCH1 | T1897 | psp | 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}. |
| P46734 | MAP2K3 | T222 | psp | Dual specificity mitogen-activated protein kinase kinase 3 (MAP kinase kinase 3) (MAPKK 3) (EC 2.7.12.2) (MAPK/ERK kinase 3) (MEK 3) (Stress-activated protein kinase kinase 2) (SAPK kinase 2) (SAPKK-2) (SAPKK2) | Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. {ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8622669}. |
| P46777 | RPL5 | T177 | ochoa | Large ribosomal subunit protein uL18 (60S ribosomal protein L5) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. 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. 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. 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:23636399, 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). {ECO:0000269|PubMed:12962325, ECO:0000269|PubMed:19061985, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:24120868}. |
| P46783 | RPS10 | T118 | 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}. |
| P46821 | MAP1B | T1069 | 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}. |
| P48444 | ARCN1 | T196 | 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}. |
| P48735 | IDH2 | T341 | ochoa | Isocitrate dehydrogenase [NADP], mitochondrial (IDH) (EC 1.1.1.42) (ICD-M) (IDP) (NADP(+)-specific ICDH) (Oxalosuccinate decarboxylase) | Plays a role in intermediary metabolism and energy production (PubMed:19228619, PubMed:22416140). It may tightly associate or interact with the pyruvate dehydrogenase complex (PubMed:19228619, PubMed:22416140). {ECO:0000269|PubMed:19228619, ECO:0000269|PubMed:22416140}. |
| P49006 | MARCKSL1 | T54 | ochoa | MARCKS-related protein (MARCKS-like protein 1) (Macrophage myristoylated alanine-rich C kinase substrate) (Mac-MARCKS) (MacMARCKS) | Controls cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation (PubMed:22751924). When unphosphorylated, induces cell migration (By similarity). When phosphorylated by MAPK8, induces actin bundles formation and stabilization, thereby reducing actin plasticity, hence restricting cell movement, including neuronal migration (By similarity). May be involved in coupling the protein kinase C and calmodulin signal transduction systems (By similarity). {ECO:0000250|UniProtKB:P28667, ECO:0000269|PubMed:22751924}. |
| P49327 | FASN | T1032 | psp | 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}. |
| P49755 | TMED10 | T77 | ochoa | Transmembrane emp24 domain-containing protein 10 (Protein TMED10) (21 kDa transmembrane-trafficking protein) (S31I125) (S31III125) (Tmp-21-I) (Transmembrane protein Tmp21) (p23) (p24 family protein delta-1) (p24delta1) (p24delta) | Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi (PubMed:10052452, PubMed:11726511, PubMed:16641999, PubMed:17288597, PubMed:19296914, PubMed:20427317, PubMed:21219331, PubMed:27569046). The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes (PubMed:10052452). Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side (PubMed:20427317, PubMed:27569046). Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles (PubMed:10052452, PubMed:10852829, PubMed:12237308). In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (PubMed:20427317, PubMed:27569046). Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment (PubMed:11726511). Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (PubMed:17288597). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (By similarity). On Golgi membranes, acts as a primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation (PubMed:11726511). Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus (PubMed:19296914). Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization (PubMed:21219331). In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC (PubMed:32272059). Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9 (PubMed:32272059). Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (PubMed:16641999). {ECO:0000250|UniProtKB:Q28735, ECO:0000250|UniProtKB:Q63584, ECO:0000269|PubMed:10052452, ECO:0000269|PubMed:10852829, ECO:0000269|PubMed:11726511, ECO:0000269|PubMed:12237308, ECO:0000269|PubMed:16641999, ECO:0000269|PubMed:17288597, ECO:0000269|PubMed:19296914, ECO:0000269|PubMed:20427317, ECO:0000269|PubMed:21219331, ECO:0000269|PubMed:27569046, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:10052452}. |
| P49792 | RANBP2 | T1156 | 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 | T921 | 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}. |
| P49959 | MRE11 | T597 | psp | 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}. |
| P50461 | CSRP3 | T82 | ochoa | Cysteine and glycine-rich protein 3 (Cardiac LIM protein) (Cysteine-rich protein 3) (CRP3) (LIM domain protein, cardiac) (Muscle LIM protein) | Positive regulator of myogenesis. Acts as a cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190, PubMed:24934443). Proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (PubMed:24934443). In vitro can inhibit PKC/PRKCA activity (PubMed:27353086). Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity). {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24934443, ECO:0000269|PubMed:27353086}.; FUNCTION: [Isoform 2]: May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation. By association with isoform 1 and thus changing the CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-mediated F-actin depolymerization. {ECO:0000269|PubMed:24860983}. |
| P50461 | CSRP3 | T84 | ochoa | Cysteine and glycine-rich protein 3 (Cardiac LIM protein) (Cysteine-rich protein 3) (CRP3) (LIM domain protein, cardiac) (Muscle LIM protein) | Positive regulator of myogenesis. Acts as a cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190, PubMed:24934443). Proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (PubMed:24934443). In vitro can inhibit PKC/PRKCA activity (PubMed:27353086). Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity). {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24934443, ECO:0000269|PubMed:27353086}.; FUNCTION: [Isoform 2]: May play a role in early sarcomere organization. Overexpression in myotubes negatively regulates myotube differentiation. By association with isoform 1 and thus changing the CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-mediated F-actin depolymerization. {ECO:0000269|PubMed:24860983}. |
| P50851 | LRBA | T1494 | 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}. |
| P51003 | PAPOLA | T109 | 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}. |
| P51451 | BLK | T390 | ochoa | Tyrosine-protein kinase Blk (EC 2.7.10.2) (B lymphocyte kinase) (p55-Blk) | Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). {ECO:0000250|UniProtKB:P16277, ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:8756631}. |
| P51610 | HCFC1 | T502 | 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}. |
| P51617 | IRAK1 | T209 | psp | Interleukin-1 receptor-associated kinase 1 (IRAK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}. |
| P51911 | CNN1 | T170 | ochoa | Calponin-1 (Basic calponin) (Calponin H1, smooth muscle) | 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 (By similarity). {ECO:0000250}. |
| P52179 | MYOM1 | T803 | 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. |
| P52564 | MAP2K6 | T211 | psp | Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. {ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11727828, ECO:0000269|PubMed:15550393, ECO:0000269|PubMed:20869211, ECO:0000269|PubMed:8622669, ECO:0000269|PubMed:8626699, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9218798}. |
| P52597 | HNRNPF | T238 | ochoa | 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}. |
| P52926 | HMGA2 | T40 | ochoa | High mobility group protein HMGI-C (High mobility group AT-hook protein 2) | Functions as a transcriptional regulator. Functions in cell cycle regulation through CCNA2. Plays an important role in chromosome condensation during the meiotic G2/M transition of spermatocytes. Plays a role in postnatal myogenesis, is involved in satellite cell activation (By similarity). Positively regulates IGF2 expression through PLAG1 and in a PLAG1-independent manner (PubMed:28796236). {ECO:0000250|UniProtKB:P52927, ECO:0000269|PubMed:14645522, ECO:0000269|PubMed:28796236}. |
| P53778 | MAPK12 | T183 | ochoa | 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}. |
| P54296 | MYOM2 | T77 | 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 | T178 | 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}. |
| P55011 | SLC12A2 | T203 | psp | 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}. |
| P55196 | AFDN | T1202 | ochoa | Afadin (ALL1-fused gene from chromosome 6 protein) (Protein AF-6) (Afadin adherens junction formation factor) | Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011). {ECO:0000250|UniProtKB:O35889, ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:30463011}. |
| P55209 | NAP1L1 | T64 | ochoa | Nucleosome assembly protein 1-like 1 (NAP-1-related protein) (hNRP) | Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly (PubMed:20002496, PubMed:21211722, PubMed:26841755). Also participates in several important DNA repair mechanisms: greatly enhances ERCC6-mediated chromatin remodeling which is essential for transcription-coupled nucleotide excision DNA repair (PubMed:28369616). Also stimulates homologous recombination (HR) by RAD51 and RAD54 which is essential in mitotic DNA double strand break (DSB) repair (PubMed:24798879). Plays a key role in the regulation of embryonic neurogenesis (By similarity). Promotes the proliferation of neural progenitors and inhibits neuronal differentiation during cortical development (By similarity). Regulates neurogenesis via the modulation of RASSF10; regulates RASSF10 expression by promoting SETD1A-mediated H3K4 methylation at the RASSF10 promoter (By similarity). {ECO:0000250|UniProtKB:P28656, ECO:0000269|PubMed:20002496, ECO:0000269|PubMed:21211722, ECO:0000269|PubMed:24798879, ECO:0000269|PubMed:26841755, ECO:0000269|PubMed:28369616}.; FUNCTION: (Microbial infection) Positively regulates Epstein-Barr virus reactivation in epithelial cells through the induction of viral BZLF1 expression. {ECO:0000269|PubMed:23691099}.; FUNCTION: (Microbial infection) Together with human herpesvirus 8 protein LANA1, assists the proper assembly of the nucleosome on the replicated viral DNA. {ECO:0000269|PubMed:27599637}. |
| P56856 | CLDN18 | T229 | 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}. |
| P57721 | PCBP3 | T159 | 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}. |
| P57764 | GSDMD | T190 | 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}. |
| P60201 | PLP1 | T118 | ochoa | Myelin proteolipid protein (PLP) (Lipophilin) | This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin. |
| P60709 | ACTB | T318 | 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}. |
| P61978 | HNRNPK | T390 | 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}. |
| P62701 | RPS4X | T184 | 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}. |
| P62736 | ACTA2 | T320 | ochoa | Actin, aortic smooth muscle (EC 3.6.4.-) (Alpha-actin-2) (Cell growth-inhibiting gene 46 protein) [Cleaved into: Actin, aortic smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P62879 | GNB2 | T143 | ochoa | Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (G protein subunit beta-2) (Transducin beta chain 2) | Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. |
| P62937 | PPIA | T119 | 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}. |
| P63261 | ACTG1 | T318 | 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}. |
| P63267 | ACTG2 | T319 | ochoa | Actin, gamma-enteric smooth muscle (EC 3.6.4.-) (Alpha-actin-3) (Gamma-2-actin) (Smooth muscle gamma-actin) [Cleaved into: Actin, gamma-enteric smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P63279 | UBE2I | T35 | psp | SUMO-conjugating enzyme UBC9 (EC 2.3.2.-) (RING-type E3 SUMO transferase UBC9) (SUMO-protein ligase) (Ubiquitin carrier protein 9) (Ubiquitin carrier protein I) (Ubiquitin-conjugating enzyme E2 I) (Ubiquitin-protein ligase I) (p18) | Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation. Sumoylates p53/TP53 at 'Lys-386'. Mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity (PubMed:26620705). {ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:17466333, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:19744555, ECO:0000269|PubMed:20077568, ECO:0000269|PubMed:26524494, ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:8668529}. |
| P67809 | YBX1 | T43 | 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}. |
| P68032 | ACTC1 | T320 | ochoa | Actin, alpha cardiac muscle 1 (EC 3.6.4.-) (Alpha-cardiac actin) [Cleaved into: Actin, alpha cardiac muscle 1, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68104 | EEF1A1 | T24 | ochoa | 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}. |
| P68104 | EEF1A1 | T269 | ochoa | 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}. |
| P68104 | EEF1A1 | T287 | ochoa | 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}. |
| P68104 | EEF1A1 | T432 | ochoa|psp | 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}. |
| P68133 | ACTA1 | T320 | ochoa | Actin, alpha skeletal muscle (EC 3.6.4.-) (Alpha-actin-1) [Cleaved into: Actin, alpha skeletal muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68363 | TUBA1B | T56 | 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}. |
| P68371 | TUBB4B | T107 | 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. |
| P68431 | H3C1 | T46 | ochoa | Histone H3.1 (Histone H3/a) (Histone H3/b) (Histone H3/c) (Histone H3/d) (Histone H3/f) (Histone H3/h) (Histone H3/i) (Histone H3/j) (Histone H3/k) (Histone H3/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. |
| P78559 | MAP1A | T1084 | 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. |
| P79483 | HLA-DRB3 | T214 | ochoa | HLA class II histocompatibility antigen, DR beta 3 chain (MHC class II antigen DRB3) | A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB3-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:16148104, PubMed:19531622, PubMed:19830726, PubMed:20368442, PubMed:22929521, PubMed:23569328, PubMed:2463305, PubMed:2788702, PubMed:30282837, PubMed:31020640, PubMed:31308093, PubMed:31333679). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (By similarity). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (By similarity). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides. The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (By similarity). {ECO:0000250|UniProtKB:P01911, ECO:0000269|PubMed:16148104, ECO:0000269|PubMed:19531622, ECO:0000269|PubMed:19830726, ECO:0000269|PubMed:20368442, ECO:0000269|PubMed:22929521, ECO:0000269|PubMed:23569328, ECO:0000269|PubMed:2463305, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:30282837, ECO:0000269|PubMed:31020640, ECO:0000269|PubMed:31308093, ECO:0000269|PubMed:31333679}.; FUNCTION: ALLELE DRB3*01:01: Exclusively presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (PubMed:19830726, PubMed:2463305, PubMed:2788702). Presents viral epitopes derived from HHV-6B U11, TRX2/U56 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). {ECO:0000269|PubMed:19830726, ECO:0000269|PubMed:2463305, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:31020640}.; FUNCTION: ALLELE DRB3*02:02 Exclusively presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (PubMed:19830726, PubMed:2788702). Upon EBV infection, presents to CD4-positive T cells latent antigen EBNA2 (PRSPTVFYNIPPMPLPPSQL) and lytic antigen BZLF1 (LTAYHVSTAPTGSWF) peptides, driving oligoclonal expansion and selection of virus-specific memory T cell subsets with cytotoxic potential to directly eliminate virus-infected B cells (PubMed:23569328, PubMed:31308093). Presents viral epitopes derived from HHV-6B U11, gB/U39 and gH/U48 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). Plays a minor role in CD4-positive T cell immune response against Dengue virus by presenting conserved peptides from capsid and non-structural NS3 proteins (PubMed:31333679). Displays peptides derived from IAV matrix protein M, implying a role in protection against IAV infection (PubMed:19830726). In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies (PubMed:22929521). Presents to Vbeta2-positive T-helper 1 cells specifically an immunodominant peptide derived from tumor antigen CTAG1A/NY-ESO-1(PGVLLKEFTVSGNILTIRLTAADHR) and confers protective memory response (PubMed:19531622, PubMed:20368442). In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a TP53 neoantigen (HYNYMCNSSCMGSMNRRPILTIITL) carrying G245S hotspot driver mutation and may mediate tumor regression (PubMed:30282837). {ECO:0000269|PubMed:19531622, ECO:0000269|PubMed:19830726, ECO:0000269|PubMed:20368442, ECO:0000269|PubMed:22929521, ECO:0000269|PubMed:23569328, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:30282837, ECO:0000269|PubMed:31020640, ECO:0000269|PubMed:31308093, ECO:0000269|PubMed:31333679}.; FUNCTION: ALLELE DRB3*03:01: Presents a series of conserved peptides derived from the M.tuberculosis PPE family of proteins, in particular PPE29 and PPE33, known to be highly immunogenic (PubMed:32341563). Presents immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and long-term protection (PubMed:2788702). Displays immunodominant viral peptides from HCV non-structural protein NS2, as part of a broad range T-helper response to resolve infection (PubMed:16148104). {ECO:0000269|PubMed:16148104, ECO:0000269|PubMed:2788702, ECO:0000269|PubMed:32341563}. |
| P83731 | RPL24 | T83 | ochoa | Large ribosomal subunit protein eL24 (60S ribosomal protein L24) (60S ribosomal protein L30) | 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}. |
| P84243 | H3-3A | T46 | ochoa | Histone H3.3 | Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. 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. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15776021, ECO:0000269|PubMed:16258499}. |
| P85299 | PRR5 | T287 | ochoa | Proline-rich protein 5 (Protein observed with Rictor-1) (Protor-1) | Associated subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals (PubMed:17461779, PubMed:17599906, PubMed:29424687). mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive (PubMed:17461779, PubMed:17599906, PubMed:29424687). mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:17461779, PubMed:17599906, PubMed:29424687). PRR5 plays an important role in regulation of PDGFRB expression and in modulation of platelet-derived growth factor signaling (PubMed:17599906). May act as a tumor suppressor in breast cancer (PubMed:15718101). {ECO:0000269|PubMed:15718101, ECO:0000269|PubMed:17461779, ECO:0000269|PubMed:17599906, ECO:0000269|PubMed:29424687}. |
| Q00536 | CDK16 | T175 | ochoa|psp | 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}. |
| Q00537 | CDK17 | T202 | 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 | T187 | 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 | T34 | 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}. |
| Q01628 | IFITM3 | T94 | ochoa | Interferon-induced transmembrane protein 3 (Dispanin subfamily A member 2b) (DSPA2b) (Interferon-inducible protein 1-8U) | IFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. Inhibits the entry of viruses to the host cell cytoplasm by preventing viral fusion with cholesterol depleted endosomes. May inactivate new enveloped viruses which buds out of the infected cell, by letting them go out with a cholesterol depleted membrane. Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV) (PubMed:26354436, PubMed:33239446, PubMed:33270927). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-mediated viral entry (PubMed:33270927). Plays a critical role in the structural stability and function of vacuolar ATPase (v-ATPase). Establishes physical contact with the v-ATPase of endosomes which is critical for proper clathrin localization and is also required for the function of the v-ATPase to lower the pH in phagocytic endosomes thus establishing an antiviral state. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation (PubMed:26354436). IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome (PubMed:26354436). Exerts opposing activities on SARS-CoV-2, including amphipathicity-dependent restriction of virus at endosomes and amphipathicity-independent enhancement of infection at the plasma membrane (PubMed:33270927). {ECO:0000269|PubMed:20064371, ECO:0000269|PubMed:20534863, ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:21177806, ECO:0000269|PubMed:21253575, ECO:0000269|PubMed:22046135, ECO:0000269|PubMed:22479637, ECO:0000269|PubMed:23601107, ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33239446, ECO:0000269|PubMed:33270927}. |
| Q01629 | IFITM2 | T93 | ochoa | Interferon-induced transmembrane protein 2 (Dispanin subfamily A member 2c) (DSPA2c) (Interferon-inducible protein 1-8D) | IFN-induced antiviral protein which inhibits the entry of viruses to the host cell cytoplasm, permitting endocytosis, but preventing subsequent viral fusion and release of viral contents into the cytosol (PubMed:26354436, PubMed:33563656). Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV) (PubMed:26354436, PubMed:33239446, PubMed:33270927, PubMed:33563656). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-mediated viral entry (PubMed:33563656). Induces cell cycle arrest and mediates apoptosis by caspase activation and in p53-independent manner. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation (PubMed:26354436). IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome (PubMed:26354436). {ECO:0000269|PubMed:19544527, ECO:0000269|PubMed:20064371, ECO:0000269|PubMed:20534863, ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:21177806, ECO:0000269|PubMed:21253575, ECO:0000269|PubMed:22479637, ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33239446, ECO:0000269|PubMed:33270927, ECO:0000269|PubMed:33563656}. |
| Q01804 | OTUD4 | T537 | 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}. |
| Q02410 | APBA1 | T89 | ochoa | Amyloid-beta A4 precursor protein-binding family A member 1 (Adapter protein X11alpha) (Neuron-specific X11 protein) (Neuronal Munc18-1-interacting protein 1) (Mint-1) | Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. 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:B2RUJ5}. |
| Q02487 | DSC2 | T783 | 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}. |
| Q02952 | AKAP12 | T523 | 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 | T548 | 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 | T723 | 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 | T834 | 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). |
| Q02978 | SLC25A11 | T95 | ochoa | Mitochondrial 2-oxoglutarate/malate carrier protein (OGCP) (alpha-oxoglutarate carrier) (Solute carrier family 25 member 11) (SLC25A11) | Catalyzes the transport of 2-oxoglutarate (alpha-oxoglutarate) across the inner mitochondrial membrane in an electroneutral exchange for malate. Can also exchange 2-oxoglutarate for other dicarboxylic acids such as malonate, succinate, maleate and oxaloacetate, although with lower affinity. Contributes to several metabolic processes, including the malate-aspartate shuttle, the oxoglutarate/isocitrate shuttle, in gluconeogenesis from lactate, and in nitrogen metabolism (By similarity). Maintains mitochondrial fusion and fission events, and the organization and morphology of cristae (PubMed:21448454). Involved in the regulation of apoptosis (By similarity). Helps protect from cytotoxic-induced apoptosis by modulating glutathione levels in mitochondria (By similarity). {ECO:0000250|UniProtKB:P22292, ECO:0000250|UniProtKB:P97700, ECO:0000250|UniProtKB:Q9CR62, ECO:0000269|PubMed:21448454}. |
| Q03252 | LMNB2 | T556 | ochoa | Lamin-B2 | 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:33033404). 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:33033404). 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:33033404). {ECO:0000269|PubMed:33033404}. |
| Q04771 | ACVR1 | T203 | psp | Activin receptor type-1 (EC 2.7.11.30) (Activin receptor type I) (ACTR-I) (Activin receptor-like kinase 2) (ALK-2) (Serine/threonine-protein kinase receptor R1) (SKR1) (TGF-B superfamily receptor type I) (TSR-I) | Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (By similarity). {ECO:0000250|UniProtKB:P15261, ECO:0000250|UniProtKB:P37172, ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22977237, ECO:0000269|PubMed:25354296, ECO:0000269|PubMed:9748228}. |
| Q05639 | EEF1A2 | T24 | ochoa | 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}. |
| Q05639 | EEF1A2 | T432 | ochoa | 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}. |
| Q06210 | GFPT1 | T262 | ochoa | 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}. |
| Q06710 | PAX8 | T291 | ochoa | Paired box protein Pax-8 | Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells. |
| Q07812 | BAX | T172 | psp | Apoptosis regulator BAX (Bcl-2-like protein 4) (Bcl2-L-4) | Plays a role in the mitochondrial apoptotic process (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:36361894, PubMed:8358790, PubMed:8521816). Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM) (PubMed:21458670). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:8358790, PubMed:8521816). Promotes activation of CASP3, and thereby apoptosis (PubMed:10772918, PubMed:11060313, PubMed:16113678, PubMed:16199525, PubMed:18948948, PubMed:21199865, PubMed:21458670, PubMed:25609812, PubMed:8358790, PubMed:8521816). {ECO:0000269|PubMed:10772918, ECO:0000269|PubMed:11060313, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:16199525, ECO:0000269|PubMed:18948948, ECO:0000269|PubMed:21199865, ECO:0000269|PubMed:21458670, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:36361894, ECO:0000269|PubMed:8358790, ECO:0000269|PubMed:8521816}. |
| Q07820 | MCL1 | T68 | 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}. |
| Q08174 | PCDH1 | T1006 | ochoa | Protocadherin-1 (Cadherin-like protein 1) (Protocadherin-42) (PC42) | May be involved in cell-cell interaction processes and in cell adhesion. |
| Q08211 | DHX9 | T887 | 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}. |
| Q08379 | GOLGA2 | T959 | 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}. |
| Q08J23 | NSUN2 | T718 | ochoa | RNA cytosine C(5)-methyltransferase NSUN2 (EC 2.1.1.-) (Myc-induced SUN domain-containing protein) (Misu) (NOL1/NOP2/Sun domain family member 2) (Substrate of AIM1/Aurora kinase B) (mRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (tRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-, EC 2.1.1.203) (tRNA methyltransferase 4 homolog) (hTrm4) | RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847). {ECO:0000250|UniProtKB:Q1HFZ0, ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:22995836, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31199786, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:34556860}. |
| Q09019 | DMWD | T410 | ochoa | Dystrophia myotonica WD repeat-containing protein (Dystrophia myotonica-containing WD repeat motif protein) (Protein 59) (Protein DMR-N9) | Regulator of the deubiquitinating USP12/DMWD/WDR48 complex (PubMed:33844468). Functions as a cofactor that promotes USP12 enzymatic activity (PubMed:33844468). {ECO:0000269|PubMed:33844468}. |
| Q09666 | AHNAK | T158 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T5610 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T5839 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T5845 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12802 | AKAP13 | T2467 | ochoa|psp | 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}. |
| Q13009 | TIAM1 | T340 | 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}. |
| Q13263 | TRIM28 | T690 | 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}. |
| Q13393 | PLD1 | T632 | 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}. |
| Q13428 | TCOF1 | T147 | 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 | T1179 | 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 | T1384 | 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 | T61 | 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}. |
| Q13469 | NFATC2 | T862 | 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}. |
| Q13485 | SMAD4 | T265 | psp | Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (Deletion target in pancreatic carcinoma 4) (SMAD family member 4) (SMAD 4) (Smad4) (hSMAD4) | In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. {ECO:0000250, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:9389648}. |
| Q13501 | SQSTM1 | T138 | psp | 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}. |
| Q13509 | TUBB3 | T107 | ochoa | Tubulin beta-3 chain (Tubulin beta-4 chain) (Tubulin beta-III) | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:34996871, PubMed:38305685, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:34996871, PubMed:38305685, PubMed:38609661). Below the cap, alpha-beta tubulin heterodimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). TUBB3 plays a critical role in proper axon guidance and maintenance (PubMed:20074521). Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Plays a role in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977). {ECO:0000269|PubMed:20074521, ECO:0000269|PubMed:28483977, ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| Q13541 | EIF4EBP1 | T50 | ochoa|psp | Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) (eIF4E-binding protein 1) (Phosphorylated heat- and acid-stable protein regulated by insulin 1) (PHAS-I) | Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. {ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22684010, ECO:0000269|PubMed:7935836}. |
| Q13542 | EIF4EBP2 | T50 | ochoa | Eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2) (eIF4E-binding protein 2) | Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:30765518). Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:25533957, PubMed:30765518). EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity). {ECO:0000250|UniProtKB:P70445, ECO:0000269|PubMed:25533957, ECO:0000269|PubMed:30765518}. |
| Q13554 | CAMK2B | T400 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit beta (CaM kinase II subunit beta) (CaMK-II subunit beta) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle (PubMed:16690701). In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise (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 triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (PubMed:31930741). {ECO:0000250|UniProtKB:P08413, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:31930741}. |
| Q13561 | DCTN2 | T79 | ochoa | Dynactin subunit 2 (50 kDa dynein-associated polypeptide) (Dynactin complex 50 kDa subunit) (DCTN-50) (p50 dynamitin) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (By similarity). {ECO:0000250|UniProtKB:A0A5G2QD80, ECO:0000250|UniProtKB:Q99KJ8}. |
| Q13596 | SNX1 | T48 | 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}. |
| Q13671 | RIN1 | T218 | 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}. |
| Q13761 | RUNX3 | T155 | psp | Runt-related transcription factor 3 (Acute myeloid leukemia 2 protein) (Core-binding factor subunit alpha-3) (CBF-alpha-3) (Oncogene AML-2) (Polyomavirus enhancer-binding protein 2 alpha C subunit) (PEA2-alpha C) (PEBP2-alpha C) (SL3-3 enhancer factor 1 alpha C subunit) (SL3/AKV core-binding factor alpha C subunit) | Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (By similarity). May be involved in the control of cellular proliferation and/or differentiation. In association with ZFHX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712). CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation. CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing (By similarity). Necessary for the development and survival of sensory neurons expressing parvalbumin (By similarity). {ECO:0000250|UniProtKB:Q64131, ECO:0000269|PubMed:20599712}. |
| Q13873 | BMPR2 | T823 | ochoa | Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}. |
| Q13885 | TUBB2A | T107 | 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. |
| Q13905 | RAPGEF1 | T248 | 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}. |
| Q14004 | CDK13 | T1480 | 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}. |
| Q14008 | CKAP5 | T1910 | 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}. |
| Q14126 | DSG2 | T695 | 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}. |
| Q14135 | VGLL4 | T203 | ochoa | Transcription cofactor vestigial-like protein 4 (Vgl-4) | May act as a specific coactivator for the mammalian TEFs. {ECO:0000250}. |
| Q14151 | SAFB2 | T25 | 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. |
| Q14151 | SAFB2 | T27 | 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 | T357 | 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 | T749 | 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}. |
| Q14160 | SCRIB | T936 | 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}. |
| Q14244 | MAP7 | T22 | 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}. |
| Q14247 | CTTN | T323 | 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 | T519 | 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 | T1464 | 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 | T2149 | 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 | T2305 | 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}. |
| Q14457 | BECN1 | T119 | 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}. |
| Q14511 | NEDD9 | T126 | 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}. |
| Q14524 | SCN5A | T594 | 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}. |
| Q14644 | RASA3 | T805 | 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. |
| Q14653 | IRF3 | T333 | ochoa | Interferon regulatory factor 3 (IRF-3) | Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049179, PubMed:25636800, PubMed:27302953, PubMed:31340999, PubMed:36603579, PubMed:8524823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995, PubMed:36603579, PubMed:8524823). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:36603579). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953, PubMed:36603579). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148, PubMed:36603579). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31340999, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:36603579, ECO:0000269|PubMed:8524823, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}. |
| Q14669 | TRIP12 | T1424 | 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 | T112 | 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}. |
| Q14699 | RFTN1 | T552 | ochoa | Raftlin (Cell migration-inducing gene 2 protein) (Raft-linking protein) | Involved in protein trafficking via association with clathrin and AP2 complex (PubMed:21266579, PubMed:27022195). Upon bacterial lipopolysaccharide stimulation, mediates internalization of TLR4 to endosomes in dendritic cells and macrophages; and internalization of poly(I:C) to TLR3-positive endosomes in myeloid dendritic cells and epithelial cells; resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production (PubMed:21266579, PubMed:27022195). Involved in T-cell antigen receptor-mediated signaling by regulating tyrosine kinase LCK localization, T-cell dependent antibody production and cytokine secretion (By similarity). May regulate B-cell antigen receptor-mediated signaling (PubMed:12805216). May play a pivotal role in the formation and/or maintenance of lipid rafts (PubMed:12805216). {ECO:0000250|UniProtKB:Q6A0D4, ECO:0000269|PubMed:12805216, ECO:0000269|PubMed:21266579, ECO:0000269|PubMed:27022195}. |
| Q147X3 | NAA30 | T148 | ochoa | N-alpha-acetyltransferase 30 (EC 2.3.1.256) (N-acetyltransferase 12) (N-acetyltransferase MAK3 homolog) (NatC catalytic subunit) | Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex (PubMed:19398576, PubMed:37891180). Catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly (PubMed:19398576, PubMed:37891180). N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway (PubMed:37891180). Necessary for the lysosomal localization and function of ARL8B sugeesting that ARL8B is a NatC substrate (PubMed:19398576). {ECO:0000269|PubMed:19398576, ECO:0000269|PubMed:37891180}. |
| Q14978 | NOLC1 | T665 | 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}. |
| Q14980 | NUMA1 | T1811 | ochoa|psp | 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}. |
| Q14980 | NUMA1 | T2093 | 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}. |
| Q14994 | NR1I3 | T38 | psp | Nuclear receptor subfamily 1 group I member 3 (Constitutive activator of retinoid response) (Constitutive active response) (Constitutive androstane receptor) (CAR) (Orphan nuclear receptor MB67) | Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element. |
| Q15021 | NCAPD2 | T586 | 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}. |
| Q15233 | NONO | T440 | 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}. |
| Q15365 | PCBP1 | T127 | ochoa|psp | 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 | T255 | 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 | T127 | 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}. |
| Q15375 | EPHA7 | T794 | ochoa | Ephrin type-A receptor 7 (EC 2.7.10.1) (EPH homology kinase 3) (EHK-3) (EPH-like kinase 11) (EK11) (hEK11) | 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. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 and MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269|PubMed:17726105}. |
| Q15424 | SAFB | T26 | 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}. |
| Q15722 | LTB4R | T308 | 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. |
| Q15759 | MAPK11 | T180 | psp | 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}. |
| Q15831 | STK11 | T402 | psp | Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1) (LKB1) (hLKB1) (Renal carcinoma antigen NY-REN-19) | Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250}. |
| Q16512 | PKN1 | T909 | ochoa | 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}. |
| Q16539 | MAPK14 | T180 | ochoa|psp | 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}. |
| Q16637 | SMN1 | T25 | ochoa|psp | Survival motor neuron protein (Component of gems 1) (Gemin-1) | 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 (PubMed:18984161, PubMed:9845364). 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:18984161). 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:18984161). To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate (PubMed:18984161). Within the SMN complex, SMN1 acts as a structural backbone and together with GEMIN2 it gathers the Sm complex subunits (PubMed:17178713, PubMed:21816274, PubMed:22101937). Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (PubMed:31799625). Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development (PubMed:23063131). Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:17178713, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21816274, ECO:0000269|PubMed:22101937, ECO:0000269|PubMed:23063131, ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:31799625, ECO:0000269|PubMed:9845364}. |
| Q16695 | H3-4 | T46 | ochoa | Histone H3.1t (H3/t) (H3t) (H3/g) (Histone H3.4) | 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. |
| Q16763 | UBE2S | T175 | ochoa | Ubiquitin-conjugating enzyme E2 S (EC 2.3.2.23) (E2 ubiquitin-conjugating enzyme S) (E2-EPF) (Ubiquitin carrier protein S) (Ubiquitin-conjugating enzyme E2-24 kDa) (Ubiquitin-conjugating enzyme E2-EPF5) (Ubiquitin-protein ligase S) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:19820702, PubMed:19822757, PubMed:22496338, PubMed:27259151). Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis (PubMed:19820702, PubMed:19822757, PubMed:27259151, PubMed:27910872). Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit (PubMed:19820702, PubMed:19822757, PubMed:27259151). Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as an E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A (PubMed:16819549). In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination (PubMed:20061386, PubMed:20622874). {ECO:0000269|PubMed:16819549, ECO:0000269|PubMed:19820702, ECO:0000269|PubMed:19822757, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22496338, ECO:0000269|PubMed:27259151, ECO:0000269|PubMed:27910872}. |
| Q16877 | PFKFB4 | T140 | psp | 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. |
| Q27J81 | INF2 | T1179 | ochoa | Inverted formin-2 (HBEBP2-binding protein C) | Severs actin filaments and accelerates their polymerization and depolymerization. {ECO:0000250}. |
| Q29RF7 | PDS5A | T1162 | 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 | T1178 | 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}. |
| Q2VIR3 | EIF2S3B | T21 | ochoa | 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}. |
| Q4KMQ1 | TPRN | T200 | ochoa | Taperin | Essential for hearing (By similarity). Required for maintenance of stereocilia on both inner and outer hair cells (By similarity). Necessary for the integrity of the stereociliary rootlet (By similarity). May act as an actin cytoskeleton regulator involved in the regulation of actin dynamics at the pointed end in hair cells (By similarity). Forms rings at the base of stereocilia and binds actin filaments in the stereocilia which may stabilize the stereocilia (By similarity). Acts as a strong inhibitor of PPP1CA phosphatase activity (PubMed:23213405). Recruited to sites of DNA damage and may play a role in DNA damage repair (PubMed:23213405). {ECO:0000250|UniProtKB:A2AI08, ECO:0000269|PubMed:23213405}. |
| Q4ZG55 | GREB1 | T1150 | ochoa | Protein GREB1 (Gene regulated in breast cancer 1 protein) | May play a role in estrogen-stimulated cell proliferation. Acts as a regulator of hormone-dependent cancer growth in breast and prostate cancers. |
| Q53EL6 | PDCD4 | T126 | 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 | T620 | 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}. |
| Q53GQ0 | HSD17B12 | T56 | ochoa | Very-long-chain 3-oxoacyl-CoA reductase (EC 1.1.1.330) (17-beta-hydroxysteroid dehydrogenase 12) (17-beta-HSD 12) (3-ketoacyl-CoA reductase) (KAR) (Estradiol 17-beta-dehydrogenase 12) (EC 1.1.1.62) (Short chain dehydrogenase/reductase family 12C member 1) | Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation. {ECO:0000269|PubMed:12482854, ECO:0000269|PubMed:16166196}. |
| Q53HL2 | CDCA8 | T169 | psp | Borealin (Cell division cycle-associated protein 8) (Dasra-B) (hDasra-B) (Pluripotent embryonic stem cell-related gene 3 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. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment. {ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15260989, ECO:0000269|PubMed:16571674, ECO:0000269|PubMed:18243099}. |
| Q5F1R6 | DNAJC21 | T417 | ochoa | DnaJ homolog subfamily C member 21 (DnaJ homolog subfamily A member 5) (Protein GS3) | May act as a co-chaperone for HSP70. May play a role in ribosomal RNA (rRNA) biogenesis, possibly in the maturation of the 60S subunit. Binds the precursor 45S rRNA. {ECO:0000269|PubMed:27346687}. |
| Q5JSH3 | WDR44 | T200 | 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}. |
| Q5JSL3 | DOCK11 | T1247 | 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}. |
| Q5SXM2 | SNAPC4 | T616 | ochoa | snRNA-activating protein complex subunit 4 (SNAPc subunit 4) (Proximal sequence element-binding transcription factor subunit alpha) (PSE-binding factor subunit alpha) (PTF subunit alpha) (snRNA-activating protein complex 190 kDa subunit) (SNAPc 190 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, ECO:0000269|PubMed:9418884}. |
| Q5SXM8 | DNLZ | T158 | ochoa | DNL-type zinc finger protein (Hsp70-escort protein 1) (HEP1) (mtHsp70-escort protein) | May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation. {ECO:0000269|PubMed:23462535}. |
| Q5T200 | ZC3H13 | T82 | 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}. |
| Q5TEC6 | H3-7 | T46 | ochoa | Histone H3-7 | 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. {ECO:0000250|UniProtKB:P68431}. |
| Q5U5Q3 | MEX3C | T232 | 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}. |
| Q5U651 | RASIP1 | T304 | 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}. |
| Q5VTE0 | EEF1A1P5 | T24 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q5VTE0 | EEF1A1P5 | T269 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q5VTE0 | EEF1A1P5 | T287 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q5VTE0 | EEF1A1P5 | T432 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q5VU65 | NUP210L | T524 | ochoa | Nuclear pore membrane glycoprotein 210-like (Nucleoporin 210 kDa-like) (Nucleoporin Nup210-like) | None |
| Q5VUJ6 | LRCH2 | T360 | 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}. |
| Q5VWN6 | TASOR2 | T1014 | ochoa | Protein TASOR 2 | None |
| Q63HR2 | TNS2 | T937 | 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}. |
| Q63ZY3 | KANK2 | T143 | 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}. |
| Q63ZY3 | KANK2 | T362 | 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 | T837 | 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 | T1092 | 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 | T1148 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q684P5 | RAP1GAP2 | T541 | 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 | T637 | 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}. |
| Q6AWC2 | WWC2 | T530 | ochoa | Protein WWC2 (BH-3-only member B) (WW domain-containing protein 2) | Regulator of the Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway. Enhances phosphorylation of LATS1 and YAP1 and negatively regulates cell proliferation and organ growth due to a suppression of the transcriptional activity of YAP1, the major effector of the Hippo pathway. {ECO:0000269|PubMed:24682284}. |
| Q6IAA8 | LAMTOR1 | T48 | ochoa | Ragulator complex protein LAMTOR1 (Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1) (Lipid raft adaptor protein p18) (Protein associated with DRMs and endosomes) (p27Kip1-releasing factor from RhoA) (p27RF-Rho) | Key component of the Ragulator complex, a multiprotein complex 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:20381137, PubMed:22980980, PubMed:29158492). 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:29158492, PubMed:30181260, PubMed:31001086, PubMed:32686708, PubMed:36476874). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:20381137, PubMed:22980980, PubMed:29158492). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:31001086, PubMed:32686708). LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes (PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29285400). Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, 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). Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes (PubMed:20381137, PubMed:22980980). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (PubMed:20544018). May also play a role in RHOA activation (PubMed:19654316). {ECO:0000250|UniProtKB:Q9CQ22, ECO:0000269|PubMed:19654316, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29107538, ECO:0000269|PubMed:29123114, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:29285400, ECO:0000269|PubMed:30181260, ECO:0000269|PubMed:31001086, ECO:0000269|PubMed:32686708, ECO:0000269|PubMed:36476874}. |
| Q6ICG6 | KIAA0930 | T263 | ochoa | Uncharacterized protein KIAA0930 | None |
| Q6KC79 | NIPBL | T2667 | 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}. |
| Q6N022 | TENM4 | T2581 | 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}. |
| Q6P0Q8 | MAST2 | T63 | ochoa | 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}. |
| Q6P1L5 | FAM117B | T111 | ochoa | Protein FAM117B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 13 protein) | None |
| Q6PDB4 | ZNF880 | T424 | ochoa | Zinc finger protein 880 | None |
| Q6PEY2 | TUBA3E | T56 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E 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. |
| Q6PFW1 | PPIP5K1 | T940 | 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}. |
| Q6PKG0 | LARP1 | T68 | 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}. |
| Q6RW13 | AGTRAP | T135 | 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}. |
| Q6TCH7 | PAQR3 | T32 | psp | Progestin and adipoQ receptor family member 3 (Progestin and adipoQ receptor family member III) (Raf kinase trapping to Golgi) (RKTG) | Golgi-scaffold protein which modulates its interactors acitivies by anchoring them to the Golgi apparatus (PubMed:18547165, PubMed:26311497). Functions as a spatial regulator of RAF1 kinase by sequestrating it to the Golgi apparatus (PubMed:18547165). Acts as a positive regulator of cholesterol biosynthesis by mediating the anchoring of the SCAP:SREBP complex in the Golgi apparatus, thereby promoting SCAP:SREBF2 complex formation, potentiating SREBF2 and SREBF1 processing and enhancing lipid synthesis (PubMed:26311497). Also regulates PPARA and PPARG functions by mediating their interaction with E3 ubiquitin ligases, such as STUB1 or HUWE1, leading to their polyubiquitination and proteasome-mediated degradation (By similarity). {ECO:0000250|UniProtKB:Q6TCG8, ECO:0000269|PubMed:18547165, ECO:0000269|PubMed:26311497}. |
| Q6UUV7 | CRTC3 | T270 | 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}. |
| Q6ZNJ1 | NBEAL2 | T764 | 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}. |
| Q709C8 | VPS13C | T869 | 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}. |
| Q71DI3 | H3C15 | T46 | ochoa | Histone H3.2 (H3-clustered histone 13) (H3-clustered histone 14) (H3-clustered histone 15) (Histone H3/m) (Histone H3/o) | 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. |
| Q71U36 | TUBA1A | T56 | 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. |
| Q7KZI7 | MARK2 | T372 | 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}. |
| Q7L2J0 | MEPCE | T258 | 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}. |
| Q7Z2W4 | ZC3HAV1 | T403 | 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 | T553 | ochoa | Prickle-like protein 2 | None |
| Q7Z460 | CLASP1 | T798 | 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}. |
| Q7Z4Q2 | HEATR3 | T31 | ochoa | HEAT repeat-containing protein 3 (Symportin Syo1) (hsSyo1) | Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5) (PubMed:35213692). Required for proper erythrocyte maturation (PubMed:35213692). {ECO:0000269|PubMed:35213692}. |
| Q7Z5J4 | RAI1 | T1387 | 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 | T482 | 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}. |
| Q86SQ0 | PHLDB2 | T132 | 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}. |
| Q86U86 | PBRM1 | T346 | 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}. |
| Q86UY5 | FAM83A | T104 | ochoa | Protein FAM83A (Tumor antigen BJ-TSA-9) (Tumor-specific gene expressed in prostate protein) | Involved in mitochondrial maintenance during adipogenesis. May be acting by playing a role in the maintenance of normal mitochondrial function. {ECO:0000250|UniProtKB:Q8K2P2}. |
| Q86V81 | ALYREF | T104 | 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}. |
| Q86VY4 | TSPYL5 | T120 | psp | Testis-specific Y-encoded-like protein 5 (TSPY-like protein 5) | Involved in modulation of cell growth and cellular response to gamma radiation probably via regulation of the Akt signaling pathway. Involved in regulation of p53/TP53. Suppresses p53/TP53 protein levels and promotes its ubiquitination; the function is dependent on USP7 and independent on MDM2. Proposed to displace p53/TP53 from interaction with USP7. {ECO:0000269|PubMed:20079711, ECO:0000269|PubMed:21170034}. |
| Q8IU81 | IRF2BP1 | T459 | 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}. |
| Q8IUW5 | RELL1 | T182 | ochoa | RELT-like protein 1 | Induces activation of MAPK14/p38 cascade, when overexpressed (PubMed:28688764). Induces apoptosis, when overexpressed (PubMed:19969290). {ECO:0000269|PubMed:19969290, ECO:0000269|PubMed:28688764}. |
| Q8IVF2 | AHNAK2 | T33 | ochoa | Protein AHNAK2 | None |
| Q8IVH2 | FOXP4 | T48 | ochoa | Forkhead box protein P4 (Fork head-related protein-like A) | Transcriptional repressor that represses lung-specific expression. {ECO:0000250}. |
| Q8IVT2 | MISP | T74 | 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}. |
| Q8IW45 | NAXD | T86 | ochoa | ATP-dependent (S)-NAD(P)H-hydrate dehydratase (EC 4.2.1.93) (ATP-dependent NAD(P)HX dehydratase) (Carbohydrate kinase domain-containing protein) (NAD(P)HX dehydratase) | Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. {ECO:0000255|HAMAP-Rule:MF_03157, ECO:0000269|PubMed:30576410}. |
| Q8IWC1 | MAP7D3 | T186 | ochoa | MAP7 domain-containing protein 3 | Promotes the assembly and stability of microtubules. {ECO:0000269|PubMed:22142902, ECO:0000269|PubMed:24927501}. |
| Q8IWZ3 | ANKHD1 | T1599 | 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}. |
| Q8IZD2 | KMT2E | T1074 | 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}. |
| Q8IZL8 | PELP1 | T21 | 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}. |
| Q8N196 | SIX5 | T275 | ochoa | Homeobox protein SIX5 (DM locus-associated homeodomain protein) (Sine oculis homeobox homolog 5) | Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity). {ECO:0000250}. |
| Q8N1G0 | ZNF687 | T1120 | ochoa | Zinc finger protein 687 | May be involved in transcriptional regulation. |
| Q8N1W1 | ARHGEF28 | T522 | ochoa | Rho guanine nucleotide exchange factor 28 (190 kDa guanine nucleotide exchange factor) (p190-RhoGEF) (p190RhoGEF) (Rho guanine nucleotide exchange factor) | Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Also functions in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity). {ECO:0000250}. |
| Q8N3J3 | HROB | T369 | 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}. |
| Q8N8Z6 | DCBLD1 | T557 | ochoa | Discoidin, CUB and LCCL domain-containing protein 1 | None |
| Q8NB78 | KDM1B | T243 | ochoa | Lysine-specific histone demethylase 2 (EC 1.14.99.66) (Flavin-containing amine oxidase domain-containing protein 1) (Lysine-specific histone demethylase 1B) | Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of GLYR1 to achieve such activity, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes (PubMed:30970244). {ECO:0000269|PubMed:23260659, ECO:0000269|PubMed:23357850, ECO:0000269|PubMed:30970244}. |
| Q8NDV7 | TNRC6A | T736 | 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 | T682 | ochoa | Metal transporter CNNM3 (Ancient conserved domain-containing protein 3) (Cyclin-M3) | Probable metal transporter. {ECO:0000250}. |
| Q8NG31 | KNL1 | T1155 | psp | Outer kinetochore KNL1 complex subunit KNL1 (ALL1-fused gene from chromosome 15q14 protein) (AF15q14) (Bub-linking kinetochore protein) (Blinkin) (Cancer susceptibility candidate gene 5 protein) (Cancer/testis antigen 29) (CT29) (Kinetochore scaffold 1) (Kinetochore-null protein 1) (Protein CASC5) (Protein D40/AF15q14) | Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}. |
| Q8TAA9 | VANGL1 | T322 | ochoa | Vang-like protein 1 (Loop-tail protein 2 homolog) (LPP2) (Strabismus 2) (Van Gogh-like protein 1) | None |
| Q8TAQ2 | SMARCC2 | T391 | ochoa | SWI/SNF complex subunit SMARCC2 (BRG1-associated factor 170) (BAF170) (SWI/SNF complex 170 kDa subunit) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C member 2) | 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 (PubMed:11018012). Can stimulate the ATPase activity of the catalytic subunit of these complexes (PubMed:10078207). May be required for CoREST dependent repression of neuronal specific gene promoters in non-neuronal cells (PubMed:12192000). 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). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (By similarity). {ECO:0000250|UniProtKB:Q6PDG5, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:11018012, ECO:0000269|PubMed:12192000, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q8TDX7 | NEK7 | T190 | ochoa | Serine/threonine-protein kinase Nek7 (EC 2.7.11.34) (Never in mitosis A-related kinase 7) (NimA-related protein kinase 7) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:19941817, PubMed:31409757). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:19941817, PubMed:26522158, PubMed:31409757). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502, PubMed:39173637). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502, PubMed:39173637). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953). {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132, ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158, ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:31409757, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637}. |
| Q8TDX7 | NEK7 | T191 | ochoa | Serine/threonine-protein kinase Nek7 (EC 2.7.11.34) (Never in mitosis A-related kinase 7) (NimA-related protein kinase 7) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:19941817, PubMed:31409757). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:19941817, PubMed:26522158, PubMed:31409757). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502, PubMed:39173637). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502, PubMed:39173637). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953). {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132, ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158, ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:31409757, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637}. |
| Q8TE67 | EPS8L3 | T421 | 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 |
| Q8TEW8 | PARD3B | T334 | ochoa | Partitioning defective 3 homolog B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 19 protein) (PAR3-beta) (Partitioning defective 3-like protein) (PAR3-L protein) | Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. |
| Q8TF76 | HASPIN | T295 | psp | Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) | Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}. |
| Q8WU20 | FRS2 | T288 | ochoa | Fibroblast growth factor receptor substrate 2 (FGFR substrate 2) (FGFR-signaling adaptor SNT) (Suc1-associated neurotrophic factor target 1) (SNT-1) | Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1. {ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:21765395}. |
| Q8WUI4 | HDAC7 | T468 | 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}. |
| Q8WUU5 | GATAD1 | T71 | ochoa | GATA zinc finger domain-containing protein 1 (Ocular development-associated gene protein) | Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3). {ECO:0000269|PubMed:20850016}. |
| Q8WWM7 | ATXN2L | T104 | 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}. |
| Q8WXG6 | MADD | T1237 | 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}. |
| Q92540 | SMG7 | T539 | ochoa | Nonsense-mediated mRNA decay factor SMG7 (SMG-7 homolog) (hSMG-7) | Plays a role in nonsense-mediated mRNA decay. Recruits UPF1 to cytoplasmic mRNA decay bodies. Together with SMG5 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. {ECO:0000269|PubMed:15546618, ECO:0000269|PubMed:15721257}. |
| Q92576 | PHF3 | T1639 | ochoa | PHD finger protein 3 | None |
| Q92630 | DYRK2 | T44 | ochoa | 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}. |
| Q92667 | AKAP1 | T562 | 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}. |
| Q92729 | PTPRU | T867 | ochoa | Receptor-type tyrosine-protein phosphatase U (R-PTP-U) (EC 3.1.3.48) (Pancreatic carcinoma phosphatase 2) (PCP-2) (Protein-tyrosine phosphatase J) (PTP-J) (hPTP-J) (Protein-tyrosine phosphatase pi) (PTP pi) (Protein-tyrosine phosphatase receptor omicron) (PTP-RO) (Receptor-type protein-tyrosine phosphatase psi) (R-PTP-psi) | Tyrosine-protein phosphatase which dephosphorylates CTNNB1. Regulates CTNNB1 function both in cell adhesion and signaling. May function in cell proliferation and migration and play a role in the maintenance of epithelial integrity. May play a role in megakaryocytopoiesis. {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12501215, ECO:0000269|PubMed:16574648}. |
| Q92738 | USP6NL | T705 | ochoa | USP6 N-terminal-like protein (Related to the N-terminus of tre) (RN-tre) | Acts as a GTPase-activating protein for RAB5A and RAB43. Involved in receptor trafficking. In complex with EPS8 inhibits internalization of EGFR. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for structural integrity of the Golgi complex. {ECO:0000269|PubMed:11099046, ECO:0000269|PubMed:17562788, ECO:0000269|PubMed:17684057}. |
| Q92793 | CREBBP | T270 | 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}. |
| Q92804 | TAF15 | T222 | 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}. |
| Q92934 | BAD | T80 | 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}. |
| Q92993 | KAT5 | T195 | ochoa | Histone acetyltransferase KAT5 (EC 2.3.1.48) (60 kDa Tat-interactive protein) (Tip60) (Histone acetyltransferase HTATIP) (HIV-1 Tat interactive protein) (Lysine acetyltransferase 5) (Protein 2-hydroxyisobutyryltransferase KAT5) (EC 2.3.1.-) (Protein acetyltransferase KAT5) (EC 2.3.1.-) (Protein crotonyltransferase KAT5) (EC 2.3.1.-) (Protein lactyltransferase KAT5) (EC 2.3.1.-) (cPLA(2)-interacting protein) | Catalytic subunit of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H2A and H4 (PubMed:12776177, PubMed:14966270, PubMed:15042092, PubMed:15121871, PubMed:15310756, PubMed:16387653, PubMed:19909775, PubMed:25865756, PubMed:27153538, PubMed:29174981, PubMed:29335245, PubMed:32822602, PubMed:33076429). Histone acetylation alters nucleosome-DNA interactions and promotes interaction of the modified histones with other proteins which positively regulate transcription (PubMed:12776177, PubMed:14966270, PubMed:15042092, PubMed:15121871, PubMed:15310756). The NuA4 histone acetyltransferase complex is required for the activation of transcriptional programs associated with proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:17709392, PubMed:19783983, PubMed:32832608). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR): the complex inhibits TP53BP1 binding to chromatin via MBTD1, which recognizes and binds histone H4 trimethylated at 'Lys-20' (H4K20me), and KAT5 that catalyzes acetylation of 'Lys-15' of histone H2A (H2AK15ac), thereby blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks (PubMed:27153538, PubMed:32832608). Also involved in DSB repair by mediating acetylation of 'Lys-5' of histone H2AX (H2AXK5ac), promoting NBN/NBS1 assembly at the sites of DNA damage (PubMed:17709392, PubMed:26438602). The NuA4 complex plays a key role in hematopoietic stem cell maintenance and is required to maintain acetylated H2A.Z/H2AZ1 at MYC target genes (By similarity). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone hyperacetylation is required for histone replacement during the transition from round to elongating spermatids (By similarity). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Also acetylates non-histone proteins, such as BMAL1, ATM, AURKB, CHKA, CGAS, ERCC4/XPF, LPIN1, TP53/p53, NDC80/HEC1, NR1D2, RAN, SOX4, FOXP3, SQSTM1, ULK1 and RUBCNL/Pacer (PubMed:16141325, PubMed:17189187, PubMed:17360565, PubMed:17996965, PubMed:24835996, PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:30704899, PubMed:31857589, PubMed:32034146, PubMed:32817552, PubMed:34077757). Directly acetylates and activates ATM (PubMed:16141325). Promotes nucleotide excision repair (NER) by mediating acetylation of ERCC4/XPF, thereby promoting formation of the ERCC4-ERCC1 complex (PubMed:32034146). Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2 (PubMed:17996965). Acts as a regulator of regulatory T-cells (Treg) by catalyzing FOXP3 acetylation, thereby promoting FOXP3 transcriptional repressor activity (PubMed:17360565, PubMed:24835996). Involved in skeletal myoblast differentiation by mediating acetylation of SOX4 (PubMed:26291311). Catalyzes acetylation of APBB1/FE65, increasing its transcription activator activity (PubMed:33938178). Promotes transcription elongation during the activation phase of the circadian cycle by catalyzing acetylation of BMAL1, promoting elongation of circadian transcripts (By similarity). Together with GSK3 (GSK3A or GSK3B), acts as a regulator of autophagy: phosphorylated at Ser-86 by GSK3 under starvation conditions, leading to activate acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Acts as a regulator of the cGAS-STING innate antiviral response by catalyzing acetylation the N-terminus of CGAS, thereby promoting CGAS DNA-binding and activation (PubMed:32817552). Also regulates lipid metabolism by mediating acetylation of CHKA or LPIN1 (PubMed:34077757). Promotes lipolysis of lipid droplets following glucose deprivation by mediating acetylation of isoform 1 of CHKA, thereby promoting monomerization of CHKA and its conversion into a tyrosine-protein kinase (PubMed:34077757). Acts as a regulator of fatty-acid-induced triacylglycerol synthesis by catalyzing acetylation of LPIN1, thereby promoting the synthesis of diacylglycerol (PubMed:29765047). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), S-lactoyl-CoA (lactyl-CoA) and 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), and is able to mediate protein crotonylation, lactylation and 2-hydroxyisobutyrylation, respectively (PubMed:29192674, PubMed:34608293, PubMed:38961290). Acts as a key regulator of chromosome segregation and kinetochore-microtubule attachment during mitosis by mediating acetylation or crotonylation of target proteins (PubMed:26829474, PubMed:29040603, PubMed:30409912, PubMed:34608293). Catalyzes acetylation of AURKB at kinetochores, increasing AURKB activity and promoting accurate chromosome segregation in mitosis (PubMed:26829474). Acetylates RAN during mitosis, promoting microtubule assembly at mitotic chromosomes (PubMed:29040603). Acetylates NDC80/HEC1 during mitosis, promoting robust kinetochore-microtubule attachment (PubMed:30409912). Catalyzes crotonylation of MAPRE1/EB1, thereby ensuring accurate spindle positioning in mitosis (PubMed:34608293). Catalyzes lactylation of NBN/NBS1 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290). {ECO:0000250|UniProtKB:Q8CHK4, ECO:0000269|PubMed:12776177, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15121871, ECO:0000269|PubMed:15310756, ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17709392, ECO:0000269|PubMed:17996965, ECO:0000269|PubMed:19783983, ECO:0000269|PubMed:19909775, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:24835996, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:26291311, ECO:0000269|PubMed:26438602, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:29040603, ECO:0000269|PubMed:29174981, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:32034146, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:32822602, ECO:0000269|PubMed:32832608, ECO:0000269|PubMed:33076429, ECO:0000269|PubMed:33938178, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:38961290}.; FUNCTION: (Microbial infection) Catalyzes the acetylation of flavivirus NS3 protein to modulate their RNA-binding and -unwinding activities leading to facilitate viral replication. {ECO:0000269|PubMed:37478852}. |
| Q92997 | DVL3 | T133 | 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}. |
| Q93052 | LPP | T316 | ochoa | Lipoma-preferred partner (LIM domain-containing preferred translocation partner in lipoma) | May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295}. |
| Q969Z4 | RELT | T223 | 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}. |
| Q96A00 | PPP1R14A | T38 | psp | Protein phosphatase 1 regulatory subunit 14A (17 kDa PKC-potentiated inhibitory protein of PP1) (Protein kinase C-potentiated inhibitor protein of 17 kDa) (CPI-17) | Inhibitor of PPP1CA. Has over 1000-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction. |
| Q96A54 | ADIPOR1 | T24 | psp | Adiponectin receptor protein 1 (Progestin and adipoQ receptor family member 1) (Progestin and adipoQ receptor family member I) | Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:12802337, PubMed:25855295). Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. Has high affinity for globular adiponectin and low affinity for full-length adiponectin (By similarity). {ECO:0000250|UniProtKB:Q91VH1, ECO:0000269|PubMed:12802337, ECO:0000269|PubMed:25855295}. |
| Q96AE4 | FUBP1 | T151 | ochoa | 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}. |
| Q96AG3 | SLC25A46 | T35 | ochoa | Mitochondrial outer membrane protein SLC25A46 (Solute carrier family 25 member 46) | Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization (PubMed:26168012, PubMed:27390132, PubMed:27543974). May regulate the assembly of the MICOS (mitochondrial contact site and cristae organizing system) complex which is essential to the biogenesis and dynamics of mitochondrial cristae, the inwards folds of the inner mitochondrial membrane (PubMed:27390132). Through its interaction with the EMC (endoplasmic reticulum membrane protein complex), could regulate mitochondrial lipid homeostasis and thereby mitochondrial fission (PubMed:27390132). {ECO:0000269|PubMed:26168012, ECO:0000269|PubMed:27390132, ECO:0000269|PubMed:27543974}. |
| Q96B97 | SH3KBP1 | T593 | 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}. |
| Q96C90 | PPP1R14B | T57 | psp | Protein phosphatase 1 regulatory subunit 14B (Phospholipase C-beta-3 neighbouring gene protein) | Inhibitor of PPP1CA. Has over 50-fold higher inhibitory activity when phosphorylated (By similarity). {ECO:0000250}. |
| Q96CW1 | AP2M1 | T156 | ochoa|psp | AP-2 complex subunit mu (AP-2 mu chain) (Adaptin-mu2) (Adaptor protein complex AP-2 subunit mu) (Adaptor-related protein complex 2 subunit mu) (Clathrin assembly protein complex 2 mu medium chain) (Clathrin coat assembly protein AP50) (Clathrin coat-associated protein AP50) (HA2 50 kDa subunit) (Plasma membrane adaptor AP-2 50 kDa protein) | Component of the adaptor protein complex 2 (AP-2) (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis (PubMed:16581796). AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules (By similarity). AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (PubMed:19033387). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs (By similarity). The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at Thr-156 in membrane-associated AP-2 (PubMed:11877457). The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (PubMed:11877457). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity). {ECO:0000250|UniProtKB:P84092, ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:12694563, ECO:0000269|PubMed:12952941, ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:14985334, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:16581796, ECO:0000269|PubMed:19033387, ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:31104773}. |
| Q96HE9 | PRR11 | T323 | ochoa | Proline-rich protein 11 | Plays a critical role in cell cycle progression. {ECO:0000269|PubMed:23246489}. |
| Q96HH4 | TMEM169 | T36 | ochoa | Transmembrane protein 169 | None |
| Q96II8 | LRCH3 | T59 | ochoa | DISP complex protein LRCH3 (Leucine-rich repeat and calponin homology domain-containing protein 3) | As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. {ECO:0000269|PubMed:29467281}. |
| Q96II8 | LRCH3 | T329 | ochoa | DISP complex protein LRCH3 (Leucine-rich repeat and calponin homology domain-containing protein 3) | As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. {ECO:0000269|PubMed:29467281}. |
| Q96JA1 | LRIG1 | T1034 | 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}. |
| Q96KQ7 | EHMT2 | T252 | 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}. |
| Q96NW4 | ANKRD27 | T1023 | ochoa | Ankyrin repeat domain-containing protein 27 (VPS9 domain-containing protein) | May be a guanine exchange factor (GEF) for Rab21, Rab32 and Rab38 and regulate endosome dynamics (PubMed:16525121, PubMed:18477474). May regulate the participation of VAMP7 in membrane fusion events; in vitro inhibits VAMP7-mediated SNARE complex formation by trapping VAMP7 in a closed, fusogenically inactive conformation (PubMed:23104059). Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with Rab32, Rab38 and VAMP7 (By similarity). Involved in the regulation of neurite growth; the function seems to require its GEF activity, probably towards Rab21, and VAMP7 but not Rab32/38 (By similarity). Proposed to be involved in Golgi sorting of VAMP7 and transport of VAMP7 vesicles to the cell surface; the function seems to implicate kinesin heavy chain isoform 5 proteins, GOLGA4, RAB21 and MACF1 (PubMed:22705394). Required for the colocalization of VAMP7 and Rab21, probably on TGN sites (PubMed:19745841). Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with VPS29 (PubMed:24856514). Regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity). {ECO:0000250|UniProtKB:Q3UMR0, ECO:0000269|PubMed:23104059, ECO:0000269|PubMed:24856514, ECO:0000305|PubMed:16525121, ECO:0000305|PubMed:18477474, ECO:0000305|PubMed:22705394}. |
| Q96RL1 | UIMC1 | T237 | 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}. |
| Q96SN8 | CDK5RAP2 | T698 | 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}. |
| Q96ST3 | SIN3A | T24 | 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}. |
| Q96T51 | RUFY1 | T74 | ochoa | RUN and FYVE domain-containing protein 1 (FYVE-finger protein EIP1) (La-binding protein 1) (Rab4-interacting protein) (Zinc finger FYVE domain-containing protein 12) | Activating adapter involved in cargo sorting from early/recycling endosomes. Regulates retrieval of proteins from endosomes to the trans-Golgi network through interaction with the dynein-dynactin complex (PubMed:36282215). Dual effector of RAB4B and RAB14, mediates a cooperative interaction allowing endosomal tethering and fusion (PubMed:20534812). Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in early endosomal trafficking (PubMed:14617813). In oocytes, self-assembles to form a protein matrix which hold together endolysosomes, autophagosomes and proteasomes and generate non-membrane-bound compartments called endo-lysosomal vesicular assemblies (ELVAs). In immature oocytes, ELVAs sequester ubiquitinated protein aggregates and degrade them upon oocyte maturation (By similarity). {ECO:0000250|UniProtKB:Q8BIJ7, ECO:0000269|PubMed:14617813, ECO:0000269|PubMed:20534812, ECO:0000269|PubMed:36282215}. |
| Q99460 | PSMD1 | T299 | 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}. |
| Q99614 | TTC1 | T266 | ochoa | Tetratricopeptide repeat protein 1 (TPR repeat protein 1) | None |
| Q99698 | LYST | T2242 | 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}. |
| Q99728 | BARD1 | T714 | psp | BRCA1-associated RING domain protein 1 (BARD-1) (EC 2.3.2.27) (RING-type E3 ubiquitin transferase BARD1) | E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage. {ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:20351172}. |
| Q99759 | MAP3K3 | T516 | psp | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q99807 | COQ7 | T77 | ochoa | NADPH-dependent 3-demethoxyubiquinone 3-hydroxylase, mitochondrial (EC 1.14.13.253) (3-demethoxyubiquinone 3-hydroxylase (NADH)) (Timing protein clk-1 homolog) (Ubiquinone biosynthesis monooxygenase COQ7) | Catalyzes the hydroxylation of the 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone at the C6 position and participates in the biosynthesis of ubiquinone (Probable). Catalyzes the reaction through a substrate-mediated reduction pathway, whereby NADH shuttles electrons to 5-methoxy-2-methyl-3-(all-trans-decaprenyl)benzoquinone, which then transfers the electrons to the two Fe(3+) centers (PubMed:23445365). The binding of 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone (DMQn) mediates reduction of the diiron center by nicotinamide adenine dinucleotide (NADH) and initiates oxygen activation for subsequent DMQ hydroxylation (PubMed:23445365). The physiological substrates are 5-methoxy-2-methyl-3-(all-trans-nonaprenyl)benzoquinone (DMQ(9)) and 5-methoxy-2-methyl-3-(all-trans-decaprenyl)benzoquinone (DMQ(10)), however in vitro the enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency (PubMed:23445365, PubMed:28409910). Also has a structural role in the COQ enzyme complex, stabilizing other COQ polypeptides. Involved in lifespan determination in a ubiquinone-independent manner (By similarity). Plays a role in modulating mitochondrial stress responses, acting in the nucleus, perhaps via regulating gene expression, independent of its characterized mitochondrial function in ubiquinone biosynthesis (PubMed:25961505). {ECO:0000255|HAMAP-Rule:MF_03194, ECO:0000269|PubMed:23445365, ECO:0000269|PubMed:25961505, ECO:0000269|PubMed:28409910, ECO:0000305|PubMed:23445365, ECO:0000305|PubMed:28409910, ECO:0000305|PubMed:38425362}. |
| Q99848 | EBNA1BP2 | T261 | ochoa | Probable rRNA-processing protein EBP2 (EBNA1-binding protein 2) (Nucleolar protein p40) | Required for the processing of the 27S pre-rRNA. {ECO:0000250}. |
| Q99952 | PTPN18 | T378 | 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. |
| Q99959 | PKP2 | T334 | 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}. |
| Q9BQE3 | TUBA1C | T56 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C 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. |
| Q9BRP8 | PYM1 | T25 | ochoa | Partner of Y14 and mago (PYM homolog 1 exon junction complex-associated factor) (Protein wibg homolog) | Key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation. Acts as an EJC disassembly factor, allowing translation-dependent EJC removal and recycling by disrupting mature EJC from spliced mRNAs. Its association with the 40S ribosomal subunit probably prevents a translation-independent disassembly of the EJC from spliced mRNAs, by restricting its activity to mRNAs that have been translated. Interferes with NMD and enhances translation of spliced mRNAs, probably by antagonizing EJC functions. May bind RNA; the relevance of RNA-binding remains unclear in vivo, RNA-binding was detected by PubMed:14968132, while PubMed:19410547 did not detect RNA-binding activity independently of the EJC. {ECO:0000269|PubMed:18026120, ECO:0000269|PubMed:19410547}. |
| Q9BRP8 | PYM1 | T147 | ochoa | Partner of Y14 and mago (PYM homolog 1 exon junction complex-associated factor) (Protein wibg homolog) | Key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation. Acts as an EJC disassembly factor, allowing translation-dependent EJC removal and recycling by disrupting mature EJC from spliced mRNAs. Its association with the 40S ribosomal subunit probably prevents a translation-independent disassembly of the EJC from spliced mRNAs, by restricting its activity to mRNAs that have been translated. Interferes with NMD and enhances translation of spliced mRNAs, probably by antagonizing EJC functions. May bind RNA; the relevance of RNA-binding remains unclear in vivo, RNA-binding was detected by PubMed:14968132, while PubMed:19410547 did not detect RNA-binding activity independently of the EJC. {ECO:0000269|PubMed:18026120, ECO:0000269|PubMed:19410547}. |
| Q9BTX1 | NDC1 | T467 | ochoa | Nucleoporin NDC1 (hNDC1) (Transmembrane protein 48) | Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane. {ECO:0000269|PubMed:16600873, ECO:0000269|PubMed:16702233}. |
| Q9BVA1 | TUBB2B | T107 | 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}. |
| Q9BW04 | SARG | T535 | ochoa | Specifically androgen-regulated gene protein | Putative androgen-specific receptor. {ECO:0000269|PubMed:15525603}. |
| Q9BWT3 | PAPOLG | T108 | ochoa | Poly(A) polymerase gamma (PAP-gamma) (EC 2.7.7.19) (Neo-poly(A) polymerase) (Neo-PAP) (Polynucleotide adenylyltransferase gamma) (SRP RNA 3'-adenylating enzyme) (Signal recognition particle RNA-adenylating enzyme) (SRP RNA-adenylating enzyme) | Responsible for the post-transcriptional adenylation of the 3'-terminal of mRNA precursors and several small RNAs including signal recognition particle (SRP) RNA, nuclear 7SK RNA, U2 small nuclear RNA, and ribosomal 5S RNA. {ECO:0000269|PubMed:11287430, ECO:0000269|PubMed:11463842}. |
| Q9BXT4 | TDRD1 | T681 | 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}. |
| Q9BY11 | PACSIN1 | T332 | ochoa | 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}. |
| Q9BZ72 | PITPNM2 | T807 | 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}. |
| Q9C086 | INO80B | T87 | ochoa | INO80 complex subunit B (High mobility group AT-hook 1-like 4) (IES2 homolog) (hIes2) (PAP-1-associated protein 1) (PAPA-1) (Zinc finger HIT domain-containing protein 4) | Induces growth and cell cycle arrests at the G1 phase of the cell cycle. {ECO:0000269|PubMed:15556297}.; FUNCTION: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. {ECO:0000269|PubMed:15556297}. |
| Q9C0B5 | ZDHHC5 | T452 | 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 | T1155 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | T1206 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | T1258 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C9 | UBE2O | T1219 | 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 | T1587 | 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}. |
| Q9H0K1 | SIK2 | T489 | ochoa | Serine/threonine-protein kinase SIK2 (EC 2.7.11.1) (Qin-induced kinase) (Salt-inducible kinase 2) (SIK-2) (Serine/threonine-protein kinase SNF1-like kinase 2) | Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:23322770, PubMed:26983400). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity (PubMed:21084751, PubMed:26983400). In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (PubMed:21084751, PubMed:26983400). Also plays a role in thymic T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751, ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}. |
| Q9H2X9 | SLC12A5 | T1030 | 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}. |
| Q9H4L5 | OSBPL3 | T392 | 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}. |
| Q9H6R4 | NOL6 | T27 | ochoa | Nucleolar protein 6 (Nucleolar RNA-associated protein) (Nrap) | 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. {ECO:0000269|PubMed:11895476, ECO:0000269|PubMed:34516797}. |
| Q9H6Z4 | RANBP3 | T204 | ochoa | Ran-binding protein 3 (RanBP3) | Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP prevents binding of XPO1/CRM1 to the nuclear pore complex. Binds to CHC1/RCC1 and increases the guanine nucleotide exchange activity of CHC1/RCC1. Recruits XPO1/CRM1 to CHC1/RCC1 in a Ran-dependent manner. Negative regulator of TGF-beta signaling through interaction with the R-SMAD proteins, SMAD2 and SMAD3, and mediating their nuclear export. {ECO:0000269|PubMed:11425870, ECO:0000269|PubMed:11571268, ECO:0000269|PubMed:11932251, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9637251}. |
| Q9H792 | PEAK1 | T1078 | 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}. |
| Q9H7C9 | AAMDC | T43 | ochoa | Mth938 domain-containing protein (Adipogenesis associated Mth938 domain-containing protein) | May play a role in preadipocyte differentiation and adipogenesis. {ECO:0000250}. |
| Q9H7P6 | MVB12B | T64 | ochoa | Multivesicular body subunit 12B (ESCRT-I complex subunit MVB12B) (Protein FAM125B) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. |
| Q9H814 | PHAX | T21 | ochoa | Phosphorylated adapter RNA export protein (RNA U small nuclear RNA export adapter protein) | A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus (PubMed:39011894). Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import 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. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner (By similarity). Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Also binds to telomerase RNA. {ECO:0000250, ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:15574333}. |
| Q9HAU0 | PLEKHA5 | T60 | 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 |
| Q9HAU0 | PLEKHA5 | T399 | 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 |
| Q9HAV0 | GNB4 | T143 | ochoa | Guanine nucleotide-binding protein subunit beta-4 (Transducin beta chain 4) | Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. |
| Q9HBR0 | SLC38A10 | T639 | ochoa | Solute carrier family 38 member 10 (Amino acid transporter SLC38A10) | Facilitates bidirectional transport of amino acids. May act as a glutamate sensor that regulates glutamate-glutamine cycle and mTOR signaling in the brain. The transport mechanism remains to be elucidated. {ECO:0000250|UniProtKB:Q5I012}. |
| Q9HC98 | NEK6 | T201 | ochoa | Serine/threonine-protein kinase Nek6 (EC 2.7.11.34) (Never in mitosis A-related kinase 6) (NimA-related protein kinase 6) (Protein kinase SID6-1512) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:11516946, PubMed:14563848). Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis (PubMed:19414596). Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3 (PubMed:12054534, PubMed:20873783). Phosphorylates KIF11 to promote mitotic spindle formation (PubMed:19001501). Involved in G2/M phase cell cycle arrest induced by DNA damage (PubMed:18728393). Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (PubMed:21099361). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). {ECO:0000269|PubMed:11516946, ECO:0000269|PubMed:12054534, ECO:0000269|PubMed:14563848, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21099361, ECO:0000269|PubMed:31409757}. |
| Q9HC98 | NEK6 | T202 | ochoa|psp | Serine/threonine-protein kinase Nek6 (EC 2.7.11.34) (Never in mitosis A-related kinase 6) (NimA-related protein kinase 6) (Protein kinase SID6-1512) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:11516946, PubMed:14563848). Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis (PubMed:19414596). Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3 (PubMed:12054534, PubMed:20873783). Phosphorylates KIF11 to promote mitotic spindle formation (PubMed:19001501). Involved in G2/M phase cell cycle arrest induced by DNA damage (PubMed:18728393). Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (PubMed:21099361). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). {ECO:0000269|PubMed:11516946, ECO:0000269|PubMed:12054534, ECO:0000269|PubMed:14563848, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21099361, ECO:0000269|PubMed:31409757}. |
| Q9HDC5 | JPH1 | T153 | 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. |
| Q9NNW5 | WDR6 | T555 | ochoa | tRNA (34-2'-O)-methyltransferase regulator WDR6 (WD repeat-containing protein 6) | Together with methyltransferase FTSJ1, methylates the 2'-O-ribose of nucleotides at position 34 of the tRNA anticodon loop of substrate tRNAs (PubMed:32558197, PubMed:33771871). Required for the correct positioning of the substrate tRNA for methylation (PubMed:32558197). Required to suppress amino acid starvation-induced autophagy (PubMed:22354037). Enhances the STK11/LKB1-induced cell growth suppression activity (PubMed:17216128). {ECO:0000269|PubMed:17216128, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:32558197, ECO:0000269|PubMed:33771871}. |
| Q9NPC1 | LTB4R2 | T324 | psp | Leukotriene B4 receptor 2 (LTB4-R 2) (LTB4-R2) (LTB4 receptor JULF2) (Leukotriene B4 receptor BLT2) (Seven transmembrane receptor BLTR2) | Low-affinity receptor for leukotrienes including leukotriene B4. Mediates chemotaxis of granulocytes and macrophages. The response is mediated via G-proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTB4 > 12-epi-LTB4 > LTB5 > LTB3. |
| Q9NPF5 | DMAP1 | T435 | ochoa | DNA methyltransferase 1-associated protein 1 (DNMAP1) (DNMT1-associated protein 1) | Involved in transcription repression and activation. Its interaction with HDAC2 may provide a mechanism for histone deacetylation in heterochromatin following replication of DNA at late firing origins. Can also repress transcription independently of histone deacetylase activity. May specifically potentiate DAXX-mediated repression of glucocorticoid receptor-dependent transcription. 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. Participates in the nuclear localization of URI1 and increases its transcriptional corepressor activity. {ECO:0000269|PubMed:14665632, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:14978102, ECO:0000269|PubMed:15367675}. |
| Q9NPG3 | UBN1 | T981 | 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}. |
| Q9NPQ8 | RIC8A | T441 | ochoa | Chaperone Ric-8A (Synembryn-A) | Chaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity: folds GNAI1, GNAO1, GNA13 and GNAQ (By similarity). Does not fold G(s) G-alpha proteins GNAS nor GNAL (By similarity). Also acts as a guanine nucleotide exchange factor (GEF) for G alpha proteins by stimulating exchange of bound GDP for free GTP (By similarity). Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein (GNAI1), possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex (By similarity). Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation (PubMed:16629901). {ECO:0000250|UniProtKB:Q80ZG1, ECO:0000269|PubMed:16629901}. |
| Q9NQS5 | GPR84 | T263 | psp | G-protein coupled receptor 84 (Inflammation-related G-protein coupled receptor EX33) | G protein-coupled receptor that responds endogenously to dietary fatty acids or nutrient, specifically medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0), undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent agonists (PubMed:16966319). In immune cells, functions as a pro-inflammatory receptor via 6-OAU and promotes the expression of pro-inflammatory mediators such as TNFalpha, IL-6 and IL-12B as well as stimulating chemotactic responses through activation of signaling mediators AKT, ERK and NF-kappa-B (By similarity). In addition, triggers increased bacterial adhesion and phagocytosis in macrophages and regulates pro-inflammatory function via enhancing NLRP3 inflammasome activation (By similarity). Also plays an important role in inflammation by modulating neutrophil functions (By similarity). Mechanistically, promotes neutrophil chemotaxis, reactive oxygen species (ROS) production and degranulation via LYN-AKT/ERK pathway (By similarity). To regulate ROS, communicates with the two formyl peptide receptors FPR2 and FPR1 to control the NADPH oxidase activity in neutrophils (PubMed:33789297). {ECO:0000250|UniProtKB:Q8CIM5, ECO:0000269|PubMed:16966319, ECO:0000269|PubMed:33789297}. |
| Q9NRY5 | FAM114A2 | T137 | ochoa | Protein FAM114A2 | None |
| Q9NUG4 | CCM2L | T197 | ochoa | Cerebral cavernous malformations 2 protein-like (CCM2-like) | None |
| Q9NVH1 | DNAJC11 | T203 | ochoa | DnaJ homolog subfamily C member 11 | [Isoform 1]: Required for mitochondrial inner membrane organization. Seems to function through its association with the MICOS complex and the mitochondrial outer membrane sorting assembly machinery (SAM) complex. {ECO:0000269|PubMed:25111180, ECO:0000305}. |
| Q9NVS9 | PNPO | T238 | ochoa | Pyridoxine-5'-phosphate oxidase (EC 1.4.3.5) (Pyridoxamine-phosphate oxidase) | Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP). {ECO:0000269|PubMed:12824491, ECO:0000269|PubMed:15182361, ECO:0000269|PubMed:15772097}. |
| Q9NW75 | GPATCH2 | T50 | ochoa | G patch domain-containing protein 2 | Enhances the ATPase activity of DHX15 in vitro. {ECO:0000269|PubMed:19432882}. |
| Q9NWH9 | SLTM | T995 | 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}. |
| Q9NWZ3 | IRAK4 | T208 | psp | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q9NWZ3 | IRAK4 | T209 | psp | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q9NXR1 | NDE1 | T240 | ochoa | Nuclear distribution protein nudE homolog 1 (NudE) | Required for centrosome duplication and formation and function of the mitotic spindle. Essential for the development of the cerebral cortex. May regulate the production of neurons by controlling the orientation of the mitotic spindle during division of cortical neuronal progenitors of the proliferative ventricular zone of the brain. Orientation of the division plane perpendicular to the layers of the cortex gives rise to two proliferative neuronal progenitors whereas parallel orientation of the division plane yields one proliferative neuronal progenitor and a postmitotic neuron. A premature shift towards a neuronal fate within the progenitor population may result in an overall reduction in the final number of neurons and an increase in the number of neurons in the deeper layers of the cortex. Acts as a RAB9A/B effector that tethers RAB9-associated late endosomes to the dynein motor for their retrograde transport to the trans-Golgi network (PubMed:34793709). {ECO:0000269|PubMed:17600710, ECO:0000269|PubMed:21529752, ECO:0000269|PubMed:34793709}. |
| Q9NYL2 | MAP3K20 | T162 | psp | 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}. |
| Q9NZB2 | FAM120A | T501 | 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}. |
| Q9P0J7 | KCMF1 | T174 | 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}. |
| Q9P260 | RELCH | T85 | 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 | T183 | 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}. |
| Q9P2G1 | ANKIB1 | T749 | 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}. |
| Q9UBP0 | SPAST | T240 | ochoa | Spastin (EC 5.6.1.1) (Spastic paraplegia 4 protein) | ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:26875866}.; FUNCTION: [Isoform 1]: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. {ECO:0000269|PubMed:25875445}. |
| Q9UDT6 | CLIP2 | T355 | 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 | T707 | 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}. |
| Q9UDY2 | TJP2 | T905 | 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}. |
| Q9UGP4 | LIMD1 | T260 | 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 | T107 | 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 | T511 | 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}. |
| Q9UHN1 | POLG2 | T34 | ochoa | DNA polymerase subunit gamma-2 (DNA polymerase gamma accessory 55 kDa subunit) (p55) (Mitochondrial DNA polymerase accessory subunit) (MtPolB) (PolG-beta) | Accessory subunit of DNA polymerase gamma solely responsible for replication of mitochondrial DNA (mtDNA). Acts as an allosteric regulator of the holoenzyme activities. Enhances the polymerase activity and the processivity of POLG by increasing its interactions with the DNA template. Suppresses POLG exonucleolytic proofreading especially toward homopolymeric templates bearing mismatched termini. Binds to single-stranded DNA. {ECO:0000269|PubMed:11477093, ECO:0000269|PubMed:11477094, ECO:0000269|PubMed:11504725, ECO:0000269|PubMed:15167897, ECO:0000269|PubMed:19837034, ECO:0000269|PubMed:26056153, ECO:0000269|PubMed:30157269, ECO:0000269|PubMed:31778857, ECO:0000269|PubMed:37202477}. |
| Q9UHV7 | MED13 | T2043 | 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}. |
| Q9UJX6 | ANAPC2 | T466 | ochoa | Anaphase-promoting complex subunit 2 (APC2) (Cyclosome subunit 2) | Together with the RING-H2 protein ANAPC11, constitutes the catalytic 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:11739784, 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:11739784, PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons (By similarity). CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation (By similarity). {ECO:0000250|UniProtKB:Q8BZQ7, ECO:0000269|PubMed:11739784, ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9UKJ3 | GPATCH8 | T1072 | ochoa | G patch domain-containing protein 8 | None |
| Q9UKX2 | MYH2 | T652 | ochoa | Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}. |
| Q9UKY7 | CDV3 | T63 | ochoa | Protein CDV3 homolog | None |
| Q9ULG1 | INO80 | T1453 | ochoa | Chromatin-remodeling ATPase INO80 (hINO80) (EC 3.6.4.-) (DNA helicase-related INO80 complex homolog 1) (DNA helicase-related protein INO80) (INO80 complex subunit A) | ATPase component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and DNA repair (PubMed:16230350, PubMed:16298340, PubMed:17721549, PubMed:20237820, PubMed:20855601). Binds DNA (PubMed:16298340, PubMed:21303910). As part of the INO80 complex, remodels chromatin by shifting nucleosomes (PubMed:16230350, PubMed:21303910). Regulates transcription upon recruitment by YY1 to YY1-activated genes, where it acts as an essential coactivator (PubMed:17721549). Involved in UV-damage excision DNA repair (PubMed:20855601). The contribution to DNA double-strand break repair appears to be largely indirect through transcriptional regulation (PubMed:20687897). Involved in DNA replication (PubMed:20237820). Required for microtubule assembly during mitosis thereby regulating chromosome segregation cycle (PubMed:20237820). {ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:16298340, ECO:0000269|PubMed:17721549, ECO:0000269|PubMed:20237820, ECO:0000269|PubMed:20687897, ECO:0000269|PubMed:20855601, ECO:0000269|PubMed:21303910}. |
| Q9ULI4 | KIF26A | T806 | 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}. |
| Q9ULL8 | SHROOM4 | T590 | ochoa | Protein Shroom4 (Second homolog of apical protein) | Probable regulator of cytoskeletal architecture that plays an important role in development. May regulate cellular and cytoskeletal architecture by modulating the spatial distribution of myosin II (By similarity). {ECO:0000250, ECO:0000269|PubMed:16684770}. |
| Q9ULT0 | TTC7A | T653 | 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}. |
| Q9ULV5 | HSF4 | T471 | psp | Heat shock factor protein 4 (HSF 4) (hHSF4) (Heat shock transcription factor 4) (HSTF 4) | Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146). Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity). In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity). May be involved in DNA repair through the transcriptional regulation of RAD51 (PubMed:22587838). May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (PubMed:28981088). In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (By similarity). {ECO:0000250|UniProtKB:Q5CZP2, ECO:0000250|UniProtKB:Q9R0L1, ECO:0000269|PubMed:22587838, ECO:0000269|PubMed:23507146, ECO:0000269|PubMed:28981088}.; FUNCTION: [Isoform HSF4A]: Transcriptional repressor. {ECO:0000269|PubMed:10488131}.; FUNCTION: [Isoform HSF4B]: Transcriptional activator. {ECO:0000269|PubMed:10488131, ECO:0000269|PubMed:16371476}. |
| Q9UN70 | PCDHGC3 | Y881 | ochoa | Protocadherin gamma-C3 (PCDH-gamma-C3) (Protocadherin-2) (Protocadherin-43) (PC-43) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9UN71 | PCDHGB4 | Y870 | ochoa | Protocadherin gamma-B4 (PCDH-gamma-B4) (Cadherin-20) (Fibroblast cadherin-2) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9UPN3 | MACF1 | T7275 | ochoa | Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (620 kDa actin-binding protein) (ABP620) (Actin cross-linking family protein 7) (Macrophin-1) (Trabeculin-alpha) | [Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27693509}. |
| Q9UPN9 | TRIM33 | T638 | ochoa | E3 ubiquitin-protein ligase TRIM33 (EC 2.3.2.27) (Ectodermin homolog) (RET-fused gene 7 protein) (Protein Rfg7) (RING-type E3 ubiquitin transferase TRIM33) (Transcription intermediary factor 1-gamma) (TIF1-gamma) (Tripartite motif-containing protein 33) | Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade). {ECO:0000250, ECO:0000269|PubMed:10022127, ECO:0000269|PubMed:15820681, ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:19135894}. |
| Q9UQ35 | SRRM2 | T1345 | 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}. |
| Q9UQ88 | CDK11A | T436 | ochoa | Cyclin-dependent kinase 11A (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 2) (Cell division protein kinase 11A) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L2) | Appears to play multiple roles in cell cycle progression, cytokinesis and apoptosis. The p110 isoforms have been suggested to be involved in pre-mRNA splicing, potentially by phosphorylating the splicing protein SFRS7. The p58 isoform may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090}. |
| Q9UQC2 | GAB2 | T294 | 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}. |
| Q9UQN3 | CHMP2B | T193 | ochoa | Charged multivesicular body protein 2b (CHMP2.5) (Chromatin-modifying protein 2b) (CHMP2b) (Vacuolar protein sorting-associated protein 2-2) (Vps2-2) (hVps2-2) | Probable core 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. |
| Q9Y2I9 | TBC1D30 | T119 | ochoa | TBC1 domain family member 30 | May act as a GTPase-activating protein for Rab family protein(s). {ECO:0000305}. |
| Q9Y2K6 | USP20 | T309 | 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}. |
| Q9Y2U5 | MAP3K2 | T290 | ochoa | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| Q9Y3C6 | PPIL1 | T147 | ochoa | Peptidyl-prolyl cis-trans isomerase-like 1 (PPIase) (EC 5.2.1.8) (Rotamase PPIL1) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770, PubMed:33220177). PPIases accelerate the folding of proteins. Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:16595688). Catalyzes prolyl peptide bond isomerization in CDC40/PRP17 (PubMed:33220177). Plays an important role in embryonic brain development; this function is independent of its isomerase activity (PubMed:33220177). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:16595688, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:33220177}. |
| Q9Y3P9 | RABGAP1 | T47 | 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}. |
| Q9Y490 | TLN1 | T430 | 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 | T907 | 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 | T1749 | 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}. |
| Q9Y4D8 | HECTD4 | T1504 | ochoa | Probable E3 ubiquitin-protein ligase HECTD4 (EC 2.3.2.26) (HECT domain-containing protein 4) (HECT-type E3 ubiquitin transferase HECTD4) | 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. {ECO:0000250}. |
| Q9Y4G6 | TLN2 | T1119 | 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}. |
| Q9Y4H2 | IRS2 | T544 | 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 | T776 | 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 | T891 | 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}. |
| Q9Y4H4 | GPSM3 | T62 | ochoa | G-protein-signaling modulator 3 (Activator of G-protein signaling 4) (G18.1b) (Protein G18) | Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins. {ECO:0000269|PubMed:14656218, ECO:0000269|PubMed:15096500}. |
| Q9Y566 | SHANK1 | T1260 | ochoa | SH3 and multiple ankyrin repeat domains protein 1 (Shank1) (Somatostatin receptor-interacting protein) (SSTR-interacting protein) (SSTRIP) | Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that 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. |
| Q9Y5F6 | PCDHGC5 | Y891 | ochoa | Protocadherin gamma-C5 (PCDH-gamma-C5) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5F7 | PCDHGC4 | Y885 | ochoa | Protocadherin gamma-C4 (PCDH-gamma-C4) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5F8 | PCDHGB7 | Y876 | ochoa | Protocadherin gamma-B7 (PCDH-gamma-B7) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5F9 | PCDHGB6 | Y877 | ochoa | Protocadherin gamma-B6 (PCDH-gamma-B6) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G0 | PCDHGB5 | Y870 | ochoa | Protocadherin gamma-B5 (PCDH-gamma-B5) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G1 | PCDHGB3 | Y876 | ochoa | Protocadherin gamma-B3 (PCDH-gamma-B3) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G2 | PCDHGB2 | Y878 | ochoa | Protocadherin gamma-B2 (PCDH-gamma-B2) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G3 | PCDHGB1 | Y874 | ochoa | Protocadherin gamma-B1 (PCDH-gamma-B1) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G4 | PCDHGA9 | Y879 | ochoa | Protocadherin gamma-A9 (PCDH-gamma-A9) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G5 | PCDHGA8 | Y879 | ochoa | Protocadherin gamma-A8 (PCDH-gamma-A8) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G6 | PCDHGA7 | Y879 | ochoa | Protocadherin gamma-A7 (PCDH-gamma-A7) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G7 | PCDHGA6 | Y879 | ochoa | Protocadherin gamma-A6 (PCDH-gamma-A6) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5G8 | PCDHGA5 | Y878 | ochoa | Protocadherin gamma-A5 (PCDH-gamma-A5) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5H0 | PCDHGA3 | Y879 | ochoa | Protocadherin gamma-A3 (PCDH-gamma-A3) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5H1 | PCDHGA2 | Y879 | ochoa | Protocadherin gamma-A2 (PCDH-gamma-A2) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5H2 | PCDHGA11 | Y882 | ochoa | Protocadherin gamma-A11 (PCDH-gamma-A11) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5H3 | PCDHGA10 | Y883 | ochoa | Protocadherin gamma-A10 (PCDH-gamma-A10) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5H4 | PCDHGA1 | Y878 | ochoa | Protocadherin gamma-A1 (PCDH-gamma-A1) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9Y5K8 | ATP6V1D | T122 | ochoa | V-type proton ATPase subunit D (V-ATPase subunit D) (V-ATPase 28 kDa accessory protein) (Vacuolar proton pump subunit D) | 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: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 (By similarity). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (PubMed:21844891). {ECO:0000250|UniProtKB:P39942, ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:33065002}. |
| Q9Y5S2 | CDC42BPB | T1108 | psp | 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}. |
| Q9Y623 | MYH4 | T650 | ochoa | Myosin-4 (Myosin heavy chain 2b) (MyHC-2b) (Myosin heavy chain 4) (Myosin heavy chain IIb) (MyHC-IIb) (Myosin heavy chain, skeletal muscle, fetal) | Muscle contraction. |
| Q9Y624 | F11R | T273 | psp | Junctional adhesion molecule A (JAM-A) (Junctional adhesion molecule 1) (JAM-1) (Platelet F11 receptor) (Platelet adhesion molecule 1) (PAM-1) (CD antigen CD321) | Seems to play a role in epithelial tight junction formation. Appears early in primordial forms of cell junctions and recruits PARD3 (PubMed:11489913). The association of the PARD6-PARD3 complex may prevent the interaction of PARD3 with JAM1, thereby preventing tight junction assembly (By similarity). Plays a role in regulating monocyte transmigration involved in integrity of epithelial barrier (By similarity). Ligand for integrin alpha-L/beta-2 involved in memory T-cell and neutrophil transmigration (PubMed:11812992). Involved in platelet activation (PubMed:10753840). {ECO:0000250|UniProtKB:O88792, ECO:0000269|PubMed:10753840, ECO:0000269|PubMed:11489913, ECO:0000269|PubMed:11812992}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus sigma-1. {ECO:0000269|PubMed:11239401}.; FUNCTION: (Microbial infection) Acts as a receptor for Human Rotavirus strain Wa. {ECO:0000269|PubMed:25481868}. |
| Q9Y6G9 | DYNC1LI1 | T484 | 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 | T168 | 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}. |
| Q9Y6Q5 | AP1M2 | T223 | ochoa | AP-1 complex subunit mu-2 (AP-mu chain family member mu1B) (Adaptor protein complex AP-1 subunit mu-2) (Adaptor-related protein complex 1 subunit mu-2) (Clathrin assembly protein complex 1 mu-2 medium chain 2) (Golgi adaptor HA1/AP1 adaptin mu-2 subunit) (Mu-adaptin 2) (Mu1B-adaptin) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. |
| Q9Y6R1 | SLC4A4 | T49 | psp | 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}. |
| P00558 | PGK1 | T394 | Sugiyama | 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}. |
| P07205 | PGK2 | T394 | Sugiyama | Phosphoglycerate kinase 2 (EC 2.7.2.3) (Phosphoglycerate kinase, testis specific) | Essential for sperm motility and male fertility (PubMed:26677959). Not required for the completion of spermatogenesis (By similarity). {ECO:0000250|UniProtKB:P09041, ECO:0000269|PubMed:26677959}. |
| P07237 | P4HB | T85 | Sugiyama | Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) | This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}. |
| Q12906 | ILF3 | T300 | Sugiyama | Interleukin enhancer-binding factor 3 (Double-stranded RNA-binding protein 76) (DRBP76) (M-phase phosphoprotein 4) (MPP4) (Nuclear factor associated with dsRNA) (NFAR) (Nuclear factor of activated T-cells 90 kDa) (NF-AT-90) (Translational control protein 80) (TCP80) | RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651, PubMed:34110282). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552). {ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:28625552, ECO:0000269|PubMed:9442054}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3. {ECO:0000269|PubMed:26891316}. |
| Q9C0C2 | TNKS1BP1 | T1323 | Sugiyama | 182 kDa tankyrase-1-binding protein | None |
| P00558 | PGK1 | T376 | Sugiyama | 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}. |
| P17174 | GOT1 | T110 | Sugiyama | Aspartate aminotransferase, cytoplasmic (cAspAT) (EC 2.6.1.1) (EC 2.6.1.3) (Cysteine aminotransferase, cytoplasmic) (Cysteine transaminase, cytoplasmic) (cCAT) (Glutamate oxaloacetate transaminase 1) (Transaminase A) | Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. In addition, catalyzes (2S)-2-aminobutanoate, a by-product in the cysteine biosynthesis pathway (PubMed:27827456). {ECO:0000269|PubMed:16039064, ECO:0000269|PubMed:21900944, ECO:0000269|PubMed:27827456}. |
| P18124 | RPL7 | T170 | Sugiyama | Large ribosomal subunit protein uL30 (60S ribosomal protein L7) | 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). Binds to G-rich structures in 28S rRNA and in mRNAs (PubMed:12962325). Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs (PubMed:12962325). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P36578 | RPL4 | T69 | Sugiyama | 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}. |
| P36578 | RPL4 | T84 | Sugiyama | 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}. |
| P50991 | CCT4 | T76 | Sugiyama | T-complex protein 1 subunit delta (TCP-1-delta) (EC 3.6.1.-) (CCT-delta) (Chaperonin containing T-complex polypeptide 1 subunit 4) (Stimulator of TAR RNA-binding) | 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}. |
| Q02543 | RPL18A | T101 | Sugiyama | Large ribosomal subunit protein eL20 (60S ribosomal protein L18a) | 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}. |
| Q6NXT2 | H3-5 | T45 | Sugiyama | Histone H3.3C (Histone H3.5) | 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. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes. {ECO:0000269|PubMed:21274551}. |
| Q96AY3 | FKBP10 | T200 | 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. |
| Q99832 | CCT7 | T64 | Sugiyama | 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}. |
| Q9Y3F4 | STRAP | T54 | Sugiyama | 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}. |
| P49792 | RANBP2 | T1098 | EPSD|PSP | 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}. |
| P62826 | RAN | T32 | Sugiyama | GTP-binding nuclear protein Ran (EC 3.6.5.-) (Androgen receptor-associated protein 24) (GTPase Ran) (Ras-like protein TC4) (Ras-related nuclear protein) | GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (PubMed:10400640, PubMed:17209048, PubMed:26272610, PubMed:27306458, PubMed:8276887, PubMed:8636225, PubMed:8692944, PubMed:8896452, PubMed:9351834, PubMed:9428644, PubMed:9822603). Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (PubMed:11336674, PubMed:26272610, PubMed:29040603, PubMed:7819259, PubMed:8636225, PubMed:8692944, PubMed:8896452, PubMed:9351834, PubMed:9428644, PubMed:9822603). Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport (PubMed:8896452, PubMed:9351834, PubMed:9428644). Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (PubMed:20485264). RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (PubMed:10408446, PubMed:29040603). Required for normal progress through mitosis (PubMed:12194828, PubMed:29040603, PubMed:8421051). The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). Acts as a negative regulator of the kinase activity of VRK1 and VRK2 (PubMed:18617507). Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases (PubMed:10400640). {ECO:0000269|PubMed:10400640, ECO:0000269|PubMed:10408446, ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17209048, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:20485264, ECO:0000269|PubMed:26272610, ECO:0000269|PubMed:27306458, ECO:0000269|PubMed:29040603, ECO:0000269|PubMed:7819259, ECO:0000269|PubMed:8276887, ECO:0000269|PubMed:8421051, ECO:0000269|PubMed:8636225, ECO:0000269|PubMed:8692944, ECO:0000269|PubMed:8896452, ECO:0000269|PubMed:9351834, ECO:0000269|PubMed:9428644, ECO:0000269|PubMed:9822603, ECO:0000305|PubMed:26272610}. |
| Q9NS23 | RASSF1 | T38 | PSP | Ras association domain-containing protein 1 | Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage. {ECO:0000269|PubMed:10888881, ECO:0000269|PubMed:11333291, ECO:0000269|PubMed:12024041, ECO:0000269|PubMed:14743218, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:15949439, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:21199877}. |
| Q9Y3Y2 | CHTOP | T212 | EPSD|PSP | Chromatin target of PRMT1 protein (Friend of PRMT1 protein) (Small arginine- and glycine-rich protein) (SRAG) | Plays an important role in the ligand-dependent activation of estrogen receptor target genes (PubMed:19858291). May play a role in the silencing of fetal globin genes (PubMed:20688955). Recruits the 5FMC complex to ZNF148, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (By similarity). Plays an important role in the tumorigenicity of glioblastoma cells. Binds to 5-hydroxymethylcytosine (5hmC) and associates with the methylosome complex containing PRMT1, PRMT5, MEP50 and ERH. The CHTOP-methylosome complex associated with 5hmC is recruited to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis (PubMed:25284789). {ECO:0000250|UniProtKB:Q9CY57, ECO:0000269|PubMed:19858291, ECO:0000269|PubMed:20688955, ECO:0000269|PubMed:25284789}.; FUNCTION: Required for effective mRNA nuclear export and is a 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. 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/NFX1 pathway. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. Stimulates DDX39B ATPase and helicase activities. In cooperation with ALYREF/THOC4 enhances NXF1 RNA binding activity (PubMed:23299939). {ECO:0000269|PubMed:23299939}. |
| P23921 | RRM1 | T555 | Sugiyama | Ribonucleoside-diphosphate reductase large subunit (EC 1.17.4.1) (Ribonucleoside-diphosphate reductase subunit M1) (Ribonucleotide reductase large subunit) | Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. |
| P53634 | CTSC | T445 | Sugiyama | Dipeptidyl peptidase 1 (EC 3.4.14.1) (Cathepsin C) (Cathepsin J) (Dipeptidyl peptidase I) (DPP-I) (DPPI) (Dipeptidyl transferase) [Cleaved into: Dipeptidyl peptidase 1 exclusion domain chain (Dipeptidyl peptidase I exclusion domain chain); Dipeptidyl peptidase 1 heavy chain (Dipeptidyl peptidase I heavy chain); Dipeptidyl peptidase 1 light chain (Dipeptidyl peptidase I light chain)] | Thiol protease (PubMed:1586157). Has dipeptidylpeptidase activity (PubMed:1586157). Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids (PubMed:1586157). Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate (PubMed:1586157). Can act as both an exopeptidase and endopeptidase (PubMed:1586157). Activates serine proteases such as elastase, cathepsin G and granzymes A and B (PubMed:8428921). {ECO:0000269|PubMed:1586157, ECO:0000269|PubMed:8428921}. |
| Q15056 | EIF4H | T100 | Sugiyama | 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}. |
| O14556 | GAPDHS | T301 | Sugiyama | Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (EC 1.2.1.12) (Spermatogenic cell-specific glyceraldehyde 3-phosphate dehydrogenase 2) (GAPDH-2) (Spermatogenic glyceraldehyde-3-phosphate dehydrogenase) | May play an important role in regulating the switch between different pathways for energy production during spermiogenesis and in the spermatozoon. Required for sperm motility and male fertility (By similarity). {ECO:0000250}. |
| P08865 | RPSA | T82 | Sugiyama | Small ribosomal subunit protein uS2 (37 kDa laminin receptor precursor) (37LRP) (37/67 kDa laminin receptor) (LRP/LR) (40S ribosomal protein SA) (67 kDa laminin receptor) (67LR) (Colon carcinoma laminin-binding protein) (Laminin receptor 1) (LamR) (Laminin-binding protein precursor p40) (LBP/p40) (Multidrug resistance-associated protein MGr1-Ag) (NEM/1CHD4) | Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate of PPP1CA. {ECO:0000255|HAMAP-Rule:MF_03016, ECO:0000269|PubMed:16263087, ECO:0000269|PubMed:6300843}.; FUNCTION: (Microbial infection) Acts as a receptor for the Adeno-associated viruses 2,3,8 and 9. {ECO:0000269|PubMed:16973587}.; FUNCTION: (Microbial infection) Acts as a receptor for the Dengue virus. {ECO:0000269|PubMed:15507651}.; FUNCTION: (Microbial infection) Acts as a receptor for the Sindbis virus. {ECO:0000269|PubMed:1385835}.; FUNCTION: (Microbial infection) Acts as a receptor for the Venezuelan equine encephalitis virus. {ECO:0000269|PubMed:1385835}.; FUNCTION: (Microbial infection) Acts as a receptor for the pathogenic prion protein. {ECO:0000269|PubMed:11689427, ECO:0000269|PubMed:9396609}.; FUNCTION: (Microbial infection) Acts as a receptor for bacteria. {ECO:0000269|PubMed:15516338}. |
| P10809 | HSPD1 | T422 | Sugiyama | 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}. |
| P31943 | HNRNPH1 | T152 | Sugiyama | 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}. |
| P55795 | HNRNPH2 | T152 | Sugiyama | 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). |
| O60664 | PLIN3 | T170 | Sugiyama | 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}. |
| P04040 | CAT | T29 | Sugiyama | Catalase (EC 1.11.1.6) | Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide (PubMed:7882369). Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells (PubMed:7882369). {ECO:0000269|PubMed:7882369}. |
| P08865 | RPSA | T94 | Sugiyama | Small ribosomal subunit protein uS2 (37 kDa laminin receptor precursor) (37LRP) (37/67 kDa laminin receptor) (LRP/LR) (40S ribosomal protein SA) (67 kDa laminin receptor) (67LR) (Colon carcinoma laminin-binding protein) (Laminin receptor 1) (LamR) (Laminin-binding protein precursor p40) (LBP/p40) (Multidrug resistance-associated protein MGr1-Ag) (NEM/1CHD4) | Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate of PPP1CA. {ECO:0000255|HAMAP-Rule:MF_03016, ECO:0000269|PubMed:16263087, ECO:0000269|PubMed:6300843}.; FUNCTION: (Microbial infection) Acts as a receptor for the Adeno-associated viruses 2,3,8 and 9. {ECO:0000269|PubMed:16973587}.; FUNCTION: (Microbial infection) Acts as a receptor for the Dengue virus. {ECO:0000269|PubMed:15507651}.; FUNCTION: (Microbial infection) Acts as a receptor for the Sindbis virus. {ECO:0000269|PubMed:1385835}.; FUNCTION: (Microbial infection) Acts as a receptor for the Venezuelan equine encephalitis virus. {ECO:0000269|PubMed:1385835}.; FUNCTION: (Microbial infection) Acts as a receptor for the pathogenic prion protein. {ECO:0000269|PubMed:11689427, ECO:0000269|PubMed:9396609}.; FUNCTION: (Microbial infection) Acts as a receptor for bacteria. {ECO:0000269|PubMed:15516338}. |
| P46776 | RPL27A | T95 | Sugiyama | Large ribosomal subunit protein uL15 (60S ribosomal protein L27a) | 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}. |
| Q9Y295 | DRG1 | T62 | Sugiyama | Developmentally-regulated GTP-binding protein 1 (DRG-1) (Neural precursor cell expressed developmentally down-regulated protein 3) (NEDD-3) (Translation factor GTPase DRG1) (TRAFAC GTPase DRG1) (EC 3.6.5.-) | Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP (PubMed:23711155, PubMed:29915238, PubMed:37179472). Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions (PubMed:23711155). When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation (PubMed:19819225, PubMed:29915238). Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions (PubMed:28855639). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155, ECO:0000269|PubMed:28855639, ECO:0000269|PubMed:29915238, ECO:0000269|PubMed:37179472}. |
| P40926 | MDH2 | T179 | Sugiyama | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| Q02790 | FKBP4 | T42 | Sugiyama | 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}. |
| O15371 | EIF3D | T46 | Sugiyama | Eukaryotic translation initiation factor 3 subunit D (eIF3d) (Eukaryotic translation initiation factor 3 subunit 7) (eIF-3-zeta) (eIF3 p66) | mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (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:18599441, PubMed:25849773). 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). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815). {ECO:0000269|PubMed:18599441, 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}. |
| P04406 | GAPDH | T103 | Sugiyama | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment 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 (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P04075 | ALDOA | T119 | Sugiyama | 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}. |
| P78371 | CCT2 | T64 | 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}. |
| O43390 | HNRNPR | T134 | Sugiyama | 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. |
| O60506 | SYNCRIP | T131 | Sugiyama | 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}. |
| O60566 | BUB1B | T600 | Sugiyama | Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (EC 2.7.11.1) (MAD3/BUB1-related protein kinase) (hBUBR1) (Mitotic checkpoint kinase MAD3L) (Protein SSK1) | Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression. {ECO:0000269|PubMed:10477750, ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:14706340, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:19411850, ECO:0000269|PubMed:19503101}. |
| O75582 | RPS6KA5 | T34 | 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}. |
| O75582 | RPS6KA5 | T718 | 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}. |
| O75676 | RPS6KA4 | T705 | 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}. |
| O43390 | HNRNPR | T142 | Sugiyama | 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. |
| O60506 | SYNCRIP | T139 | Sugiyama | 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}. |
| Q8N6T3 | ARFGAP1 | T291 | Sugiyama | 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}. |
| Q9ULX6 | AKAP8L | T267 | Sugiyama | 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}. |
| Q14697 | GANAB | T40 | 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}. |
| P49327 | FASN | T309 | 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}. |
| O60763 | USO1 | T22 | Sugiyama | 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}. |
| O94776 | MTA2 | T417 | Sugiyama | 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}. |
| P23284 | PPIB | T113 | 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}. |
| P31943 | HNRNPH1 | T282 | Sugiyama | 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}. |
| P53634 | CTSC | T431 | Sugiyama | Dipeptidyl peptidase 1 (EC 3.4.14.1) (Cathepsin C) (Cathepsin J) (Dipeptidyl peptidase I) (DPP-I) (DPPI) (Dipeptidyl transferase) [Cleaved into: Dipeptidyl peptidase 1 exclusion domain chain (Dipeptidyl peptidase I exclusion domain chain); Dipeptidyl peptidase 1 heavy chain (Dipeptidyl peptidase I heavy chain); Dipeptidyl peptidase 1 light chain (Dipeptidyl peptidase I light chain)] | Thiol protease (PubMed:1586157). Has dipeptidylpeptidase activity (PubMed:1586157). Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids (PubMed:1586157). Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate (PubMed:1586157). Can act as both an exopeptidase and endopeptidase (PubMed:1586157). Activates serine proteases such as elastase, cathepsin G and granzymes A and B (PubMed:8428921). {ECO:0000269|PubMed:1586157, ECO:0000269|PubMed:8428921}. |
| P61978 | HNRNPK | T393 | Sugiyama | 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}. |
| Q00839 | HNRNPU | T549 | Sugiyama | 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}. |
| Q5T5C0 | STXBP5 | T703 | Sugiyama | Syntaxin-binding protein 5 (Lethal(2) giant larvae protein homolog 3) (Tomosyn-1) | Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding (By similarity). {ECO:0000250}. |
| Q9BTC0 | DIDO1 | T355 | Sugiyama | 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}. |
| P04626 | ERBB2 | T1103 | Sugiyama | 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}. |
| P49419 | ALDH7A1 | T68 | Sugiyama | Alpha-aminoadipic semialdehyde dehydrogenase (Alpha-AASA dehydrogenase) (EC 1.2.1.31) (Aldehyde dehydrogenase family 7 member A1) (EC 1.2.1.3) (Antiquitin-1) (Betaine aldehyde dehydrogenase) (EC 1.2.1.8) (Delta1-piperideine-6-carboxylate dehydrogenase) (P6c dehydrogenase) | Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:20207735, ECO:0000269|PubMed:21338592}. |
| P61978 | HNRNPK | T70 | Sugiyama | 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}. |
| P05129 | PRKCG | T607 | 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}. |
| P21980 | TGM2 | T368 | Sugiyama | Protein-glutamine gamma-glutamyltransferase 2 (EC 2.3.2.13) (Erythrocyte transglutaminase) (Heart G alpha(h)) (hhG alpha(h)) (Isopeptidase TGM2) (EC 3.4.-.-) (Protein G alpha(h)) (G(h)) (Protein-glutamine deamidase TGM2) (EC 3.5.1.44) (Protein-glutamine dopaminyltransferase TGM2) (EC 2.3.1.-) (Protein-glutamine histaminyltransferase TGM2) (EC 2.3.1.-) (Protein-glutamine noradrenalinyltransferase TGM2) (EC 2.3.1.-) (Protein-glutamine serotonyltransferase TGM2) (EC 2.3.1.-) (Tissue transglutaminase) (tTG) (tTgase) (Transglutaminase C) (TG(C)) (TGC) (TGase C) (Transglutaminase H) (TGase H) (Transglutaminase II) (TGase II) (Transglutaminase-2) (TG2) (TGase-2) (hTG2) | Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively (PubMed:23941696, PubMed:31991788, PubMed:9252372). Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis (PubMed:1683874, PubMed:27270573, PubMed:28198360, PubMed:7935379, PubMed:9252372). Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:23941696, PubMed:24349085, PubMed:29618516, PubMed:30458214). Under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses (PubMed:18092889, PubMed:7592956, PubMed:7649299). When secreted, catalyzes cross-linking of proteins of the extracellular matrix, such as FN1 and SPP1 resulting in the formation of scaffolds (PubMed:12506096). Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components (PubMed:7935379, PubMed:9252372). In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (PubMed:23797785, PubMed:30867594). Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity). Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3 (PubMed:30867594, PubMed:32273471). Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription (PubMed:30867594). Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system (PubMed:32273471). Regulates vein remodeling by mediating serotonylation and subsequent inactivation of ATP2A2/SERCA2 (By similarity). Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate (PubMed:20547769, PubMed:9623982). Catalyzes specific deamidation of protein gliadin, a component of wheat gluten in the diet (PubMed:9623982). May also act as an isopeptidase cleaving the previously formed cross-links (PubMed:26250429, PubMed:27131890). Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (PubMed:8943303). {ECO:0000250|UniProtKB:P08587, ECO:0000250|UniProtKB:P21981, ECO:0000269|PubMed:12506096, ECO:0000269|PubMed:1683874, ECO:0000269|PubMed:18092889, ECO:0000269|PubMed:20547769, ECO:0000269|PubMed:23797785, ECO:0000269|PubMed:23941696, ECO:0000269|PubMed:24349085, ECO:0000269|PubMed:26250429, ECO:0000269|PubMed:27131890, ECO:0000269|PubMed:28198360, ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:30458214, ECO:0000269|PubMed:30867594, ECO:0000269|PubMed:31991788, ECO:0000269|PubMed:32273471, ECO:0000269|PubMed:7592956, ECO:0000269|PubMed:7649299, ECO:0000269|PubMed:7935379, ECO:0000269|PubMed:8943303, ECO:0000269|PubMed:9252372, ECO:0000269|PubMed:9623982, ECO:0000303|PubMed:27270573}.; FUNCTION: [Isoform 2]: Has cytotoxic activity: is able to induce apoptosis independently of its acyltransferase activity. {ECO:0000269|PubMed:17116873}. |
| P49327 | FASN | T2450 | 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}. |
| Q15398 | DLGAP5 | T401 | GPS6|EPSD | Disks large-associated protein 5 (DAP-5) (Discs large homolog 7) (Disks large-associated protein DLG7) (Hepatoma up-regulated protein) (HURP) | Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells. Mitotic phosphoprotein regulated by the ubiquitin-proteasome pathway. Key regulator of adherens junction integrity and differentiation that may be involved in CDH1-mediated adhesion and signaling in epithelial cells. {ECO:0000269|PubMed:12527899, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15145941}. |
| P11142 | HSPA8 | T425 | Sugiyama | 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}. |
| Q16719 | KYNU | T85 | Sugiyama | Kynureninase (EC 3.7.1.3) (L-kynurenine hydrolase) | Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity. {ECO:0000269|PubMed:11985583, ECO:0000269|PubMed:17300176, ECO:0000269|PubMed:28792876, ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257}. |
| P53597 | SUCLG1 | T80 | Sugiyama | Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial (EC 6.2.1.4) (EC 6.2.1.5) (Succinyl-CoA synthetase subunit alpha) (SCS-alpha) | Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and specificity for either ATP or GTP is provided by different beta subunits. {ECO:0000255|HAMAP-Rule:MF_03222, ECO:0000269|PubMed:34492704}. |
| Q15424 | SAFB | T836 | Sugiyama | 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}. |
| Q99832 | CCT7 | T362 | Sugiyama | 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}. |
| P34931 | HSPA1L | T427 | Sugiyama | Heat shock 70 kDa protein 1-like (Heat shock 70 kDa protein 1L) (Heat shock 70 kDa protein 1-Hom) (HSP70-Hom) (Heat shock protein family A member 1L) | 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). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810). {ECO:0000269|PubMed:24270810, ECO:0000303|PubMed:26865365}. |
| P08253 | MMP2 | T377 | EPSD|PSP | 72 kDa type IV collagenase (EC 3.4.24.24) (72 kDa gelatinase) (Gelatinase A) (Matrix metalloproteinase-2) (MMP-2) (TBE-1) [Cleaved into: PEX] | Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; FUNCTION: PEX, the C-terminal non-catalytic fragment of MMP2, possesses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; FUNCTION: [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways. |
| Q86VB7 | CD163 | T1072 | EPSD | Scavenger receptor cysteine-rich type 1 protein M130 (Hemoglobin scavenger receptor) (CD antigen CD163) [Cleaved into: Soluble CD163 (sCD163)] | Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Exhibits a higher affinity for complexes of hemoglobin and multimeric haptoglobin of HP*1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP*1S phenotype. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1. Isoform 3 exhibits the higher capacity for ligand endocytosis and the more pronounced surface expression when expressed in cells.; FUNCTION: After shedding, the soluble form (sCD163) may play an anti-inflammatory role, and may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions. |
| P17948 | FLT1 | T1308 | Sugiyama | 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}. |
| P61247 | RPS3A | T246 | 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}. |
| P00338 | LDHA | T220 | Sugiyama | 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}. |
| P08047 | SP1 | T579 | ELM | 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}. |
| Q9UBT2 | UBA2 | T156 | Sugiyama | SUMO-activating enzyme subunit 2 (EC 2.3.2.-) (Anthracycline-associated resistance ARX) (Ubiquitin-like 1-activating enzyme E1B) (Ubiquitin-like modifier-activating enzyme 2) | 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:11451954, ECO:0000269|PubMed:11481243, ECO:0000269|PubMed:15660128, ECO:0000269|PubMed:17643372, ECO:0000269|PubMed:19443651, ECO:0000269|PubMed:20164921}. |
| P23458 | JAK1 | T901 | Sugiyama | 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}. |
| Q14195 | DPYSL3 | T507 | EPSD | Dihydropyrimidinase-related protein 3 (DRP-3) (Collapsin response mediator protein 4) (CRMP-4) (Unc-33-like phosphoprotein 1) (ULIP-1) | Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration (By similarity). {ECO:0000250}. |
| P18545 | PDE6G | T62 | GPS6|SIGNOR|ELM|EPSD | Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma (GMP-PDE gamma) (EC 3.1.4.35) | Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones. |
| Q13153 | PAK1 | T292 | SIGNOR | Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (Alpha-PAK) (p21-activated kinase 1) (PAK-1) (p65-PAK) | Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (PubMed:12624090). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}. |
| O43776 | NARS1 | T503 | Sugiyama | Asparagine--tRNA ligase, cytoplasmic (EC 6.1.1.22) (Asparaginyl-tRNA synthetase) (AsnRS) (Asparaginyl-tRNA synthetase 1) | Catalyzes the attachment of asparagine to tRNA(Asn) in a two-step reaction: asparagine is first activated by ATP to form Asn-AMP and then transferred to the acceptor end of tRNA(Asn) (PubMed:32738225, PubMed:32788587, PubMed:9421509). In addition to its essential role in protein synthesis, acts as a signaling molecule that induced migration of CCR3-expressing cells (PubMed:12235211, PubMed:30171954). Has an essential role in the development of the cerebral cortex, being required for proper proliferation of radial glial cells (PubMed:32788587). {ECO:0000269|PubMed:12235211, ECO:0000269|PubMed:30171954, ECO:0000269|PubMed:32738225, ECO:0000269|PubMed:32788587, ECO:0000269|PubMed:9421509}. |
| P29597 | TYK2 | T919 | Sugiyama | 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}. |
| P38646 | HSPA9 | T177 | Sugiyama | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| P40925 | MDH1 | T225 | Sugiyama | Malate dehydrogenase, cytoplasmic (EC 1.1.1.37) (Aromatic alpha-keto acid reductase) (KAR) (EC 1.1.1.96) (Cytosolic malate dehydrogenase) | Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237). Catalyzes the reduction of 2-oxoglutarate to 2-hydroxyglutarate, leading to elevated reactive oxygen species (ROS) (PubMed:34012073). {ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244, ECO:0000269|PubMed:31538237}. |
| Q07065 | CKAP4 | T471 | Sugiyama | 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}. |
| P49419 | ALDH7A1 | T67 | Sugiyama | Alpha-aminoadipic semialdehyde dehydrogenase (Alpha-AASA dehydrogenase) (EC 1.2.1.31) (Aldehyde dehydrogenase family 7 member A1) (EC 1.2.1.3) (Antiquitin-1) (Betaine aldehyde dehydrogenase) (EC 1.2.1.8) (Delta1-piperideine-6-carboxylate dehydrogenase) (P6c dehydrogenase) | Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism. {ECO:0000269|PubMed:16491085, ECO:0000269|PubMed:20207735, ECO:0000269|PubMed:21338592}. |
| O43242 | PSMD3 | T55 | Sugiyama | 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}. |
| Q14152 | EIF3A | T1031 | Sugiyama | 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}. |
| O60563 | CCNT1 | T358 | 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}. |
| P46087 | NOP2 | T26 | Sugiyama | 28S rRNA (cytosine(4447)-C(5))-methyltransferase (EC 2.1.1.-) (Nucleolar protein 1) (Nucleolar protein 2 homolog) (Proliferating-cell nucleolar antigen p120) (Proliferation-associated nucleolar protein p120) | S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA (PubMed:26196125). Required for efficient rRNA processing and 60S ribosomal subunit biogenesis (PubMed:24120868, PubMed:36161484). Regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs and facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes (PubMed:36161484). May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation (PubMed:24120868). {ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:26196125, ECO:0000269|PubMed:36161484}. |
| O60610 | DIAPH1 | T1230 | Sugiyama | Protein diaphanous homolog 1 (Diaphanous-related formin-1) (DRF1) | Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (By similarity). {ECO:0000250|UniProtKB:O08808, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24781755, ECO:0000269|PubMed:26912466}. |
| O75369 | FLNB | T1585 | 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. |
| P00505 | GOT2 | T192 | Sugiyama | Aspartate aminotransferase, mitochondrial (mAspAT) (EC 2.6.1.1) (EC 2.6.1.7) (Fatty acid-binding protein) (FABP-1) (Glutamate oxaloacetate transaminase 2) (Kynurenine aminotransferase 4) (Kynurenine aminotransferase IV) (Kynurenine--oxoglutarate transaminase 4) (Kynurenine--oxoglutarate transaminase IV) (Plasma membrane-associated fatty acid-binding protein) (FABPpm) (Transaminase A) | Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids. {ECO:0000269|PubMed:31422819, ECO:0000269|PubMed:9537447}. |
| P10412 | H1-4 | T99 | Sugiyama | 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}. |
| P16401 | H1-5 | T102 | Sugiyama | 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 | T100 | Sugiyama | 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 | T99 | Sugiyama | 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}. |
| P54105 | CLNS1A | T34 | Sugiyama | 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}. |
| Q02539 | H1-1 | T102 | Sugiyama | 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}. |
| Q9NZL9 | MAT2B | T34 | Sugiyama | Methionine adenosyltransferase 2 subunit beta (Methionine adenosyltransferase II beta) (MAT II beta) (Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase) | Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine (PubMed:10644686, PubMed:23189196, PubMed:25075345). Can bind NADP (in vitro) (PubMed:23189196, PubMed:23425511). {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:23425511, ECO:0000269|PubMed:25075345}. |
| O95786 | RIGI | T671 | 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}. |
| P53778 | MAPK12 | T49 | 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}. |
| P55809 | OXCT1 | T159 | Sugiyama | Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial (SCOT) (EC 2.8.3.5) (3-oxoacid CoA-transferase 1) (Somatic-type succinyl-CoA:3-oxoacid CoA-transferase) (SCOT-s) (Succinyl-CoA:3-oxoacid CoA transferase) | Key enzyme for ketone body catabolism. Catalyzes the first, rate-limiting step of ketone body utilization in extrahepatic tissues, by transferring coenzyme A (CoA) from a donor thiolester species (succinyl-CoA) to an acceptor carboxylate (acetoacetate), and produces acetoacetyl-CoA. Acetoacetyl-CoA is further metabolized by acetoacetyl-CoA thiolase into two acetyl-CoA molecules which enter the citric acid cycle for energy production (PubMed:10964512). Forms a dimeric enzyme where both of the subunits are able to form enzyme-CoA thiolester intermediates, but only one subunit is competent to transfer the CoA moiety to the acceptor carboxylate (3-oxo acid) and produce a new acyl-CoA. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity). {ECO:0000250|UniProtKB:Q29551, ECO:0000269|PubMed:10964512}. |
| O00429 | DNM1L | T586 | Sugiyama | 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}. |
| O43175 | PHGDH | T89 | Sugiyama | D-3-phosphoglycerate dehydrogenase (3-PGDH) (EC 1.1.1.95) (2-oxoglutarate reductase) (EC 1.1.1.399) (Malate dehydrogenase) (EC 1.1.1.37) | Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:25406093}. |
| P09972 | ALDOC | T119 | Sugiyama | Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) | None |
| P52597 | HNRNPF | T282 | 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}. |
| P53365 | ARFIP2 | T76 | Sugiyama | Arfaptin-2 (ADP-ribosylation factor-interacting protein 2) (Partner of RAC1) (POR1) | Plays a role in constitutive metalloproteinase (MMP) secretion from the trans Golgi network (PubMed:26507660). May have important functions during vesicle biogenesis at certain cargo subdomains, which could be predominantly utilized by secreted MMPs, such as MMP7 and MMP2 (PubMed:26507660). Also involved in autophagy by regulating the starvation-dependent trafficking of ATG9A vesicles which deliver the phosphatidylinositol 4-kinase beta (PI4KB) to the autophagosome initiation site (PubMed:30917996, PubMed:31204568). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). In addition, plays a role in NF-kappa-B inhibition by interacting with IKBKB and IKBKG (PubMed:26296658). {ECO:0000269|PubMed:26296658, ECO:0000269|PubMed:26507660, ECO:0000269|PubMed:30917996, ECO:0000269|PubMed:31204568, ECO:0000269|PubMed:33773106}. |
| P62495 | ETF1 | T298 | Sugiyama | Eukaryotic peptide chain release factor subunit 1 (Eukaryotic release factor 1) (eRF1) (Protein Cl1) (TB3-1) | Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons (PubMed:10676813, PubMed:16777602, PubMed:24486019, PubMed:26245381, PubMed:27863242, PubMed:36638793, PubMed:7990965). The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site (PubMed:26245381, PubMed:27863242, PubMed:36638793). ETF1/ERF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA (PubMed:26245381, PubMed:27863242, PubMed:36638793). Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site and mediate hydrolysis of peptidyl-tRNA (PubMed:10676813, PubMed:16777602, PubMed:26245381, 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:19417104). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371). {ECO:0000269|PubMed:10676813, ECO:0000269|PubMed:16777602, ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:24486019, ECO:0000269|PubMed:26245381, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:30682371, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:7990965}. |
| Q9Y266 | NUDC | T56 | Sugiyama | 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}. |
| O14493 | CLDN4 | T189 | GPS6 | Claudin-4 (Clostridium perfringens enterotoxin receptor) (CPE-R) (CPE-receptor) (Williams-Beuren syndrome chromosomal region 8 protein) | Can associate with other claudins to regulate tight junction structural and functional strand dynamics (PubMed:35773259, PubMed:36008380). May coassemble with CLDN8 into tight junction strands containing anion-selective channels that convey paracellular chloride permeability in renal collecting ducts (By similarity) (PubMed:36008380). May integrate into CLDN3 strands to modulate localized tight junction barrier properties (PubMed:35773259, PubMed:36008380). May disrupt strand assembly of channel-forming CLDN2 and CLDN15 and inhibit cation conductance (PubMed:35773259, PubMed:36008380). Cannot form tight junction strands on its own (PubMed:35773259, PubMed:36008380). {ECO:0000250|UniProtKB:O35054, ECO:0000269|PubMed:35773259, ECO:0000269|PubMed:36008380}. |
| P15313 | ATP6V1B1 | T323 | Sugiyama | V-type proton ATPase subunit B, kidney isoform (V-ATPase subunit B 1) (Endomembrane proton pump 58 kDa subunit) (Vacuolar proton pump subunit B 1) | Non-catalytic 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:16769747). 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). Essential for the proper assembly and activity of V-ATPase (PubMed:16769747). In renal intercalated cells, mediates secretion of protons (H+) into the urine thereby ensuring correct urinary acidification (PubMed:16769747). Required for optimal olfactory function by mediating the acidification of the nasal olfactory epithelium (By similarity). {ECO:0000250|UniProtKB:Q91YH6, ECO:0000269|PubMed:16769747, ECO:0000303|PubMed:32001091}. |
| P21281 | ATP6V1B2 | T329 | Sugiyama | V-type proton ATPase subunit B, brain isoform (V-ATPase subunit B 2) (Endomembrane proton pump 58 kDa subunit) (HO57) (Vacuolar proton pump subunit B 2) | Non-catalytic 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: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 renal intercalated cells, can partially compensate the lack of ATP6V1B1 and mediate secretion of protons (H+) into the urine under base-line conditions but not in conditions of acid load (By similarity). {ECO:0000250|UniProtKB:P62814, ECO:0000269|PubMed:33065002, ECO:0000303|PubMed:32001091}. |
| P62701 | RPS4X | T177 | Sugiyama | 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}. |
| Q15084 | PDIA6 | T223 | 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}. |
| P10809 | HSPD1 | T79 | Sugiyama | 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}. |
| P31943 | HNRNPH1 | T287 | Sugiyama | 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}. |
| Q9NYF8 | BCLAF1 | T333 | Sugiyama | 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}. |
| P23142 | FBLN1 | T250 | Sugiyama | Fibulin-1 (FIBL-1) | Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes. Has been implicated in a role in cellular transformation and tumor invasion, it appears to be a tumor suppressor. May play a role in haemostasis and thrombosis owing to its ability to bind fibrinogen and incorporate into clots. Could play a significant role in modulating the neurotrophic activities of APP, particularly soluble APP. {ECO:0000269|PubMed:11792823, ECO:0000269|PubMed:9393974, ECO:0000269|PubMed:9466671}. |
| Q13163 | MAP2K5 | T124 | Sugiyama | Dual specificity mitogen-activated protein kinase kinase 5 (MAP kinase kinase 5) (MAPKK 5) (EC 2.7.12.2) (MAPK/ERK kinase 5) (MEK 5) | Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). {ECO:0000250|UniProtKB:Q62862, ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}. |
| P34897 | SHMT2 | T432 | 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}. |
| Q13164 | MAPK7 | T77 | Sugiyama | Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) | Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}. |
| P10809 | HSPD1 | T320 | Sugiyama | 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}. |
| Q13233 | MAP3K1 | T1400 | Sugiyama | Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1) (EC 2.3.2.27) | Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). {ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:9808624}. |
| Q13976 | PRKG1 | T269 | Sugiyama | 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}. |
| Q15084 | PDIA6 | T100 | 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}. |
| Q8NBP7 | PCSK9 | T228 | Sugiyama | 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}. |
| Q15418 | RPS6KA1 | T384 | Sugiyama | 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}. |
| P49411 | TUFM | T74 | Sugiyama | 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}. |
| Q15831 | STK11 | T395 | Sugiyama | Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1) (LKB1) (hLKB1) (Renal carcinoma antigen NY-REN-19) | Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250}. |
| P60709 | ACTB | T160 | Sugiyama | 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 | T160 | Sugiyama | 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}. |
| Q99615 | DNAJC7 | T280 | Sugiyama | DnaJ homolog subfamily C member 7 (Tetratricopeptide repeat protein 2) (TPR repeat protein 2) | Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recycling chaperone by facilitating the return of chaperone substrates to early stages of chaperoning if further folding is required. In vitro, induces ATP-independent dissociation of HSP90 but not of HSP70 from the chaperone-substrate complexes. Recruits NR1I3 to the cytoplasm (By similarity). {ECO:0000250, ECO:0000269|PubMed:12853476, ECO:0000269|PubMed:18620420}. |
| Q9H6T3 | RPAP3 | T157 | 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}. |
| O75369 | FLNB | T1444 | 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. |
| Q7L014 | DDX46 | T721 | Sugiyama | Probable ATP-dependent RNA helicase DDX46 (EC 3.6.4.13) (DEAD box protein 46) (PRP5 homolog) | 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, PubMed:36797247). 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, DDX46 plays essential roles during assembly of pre-spliceosome and proofreading of the branch site (PubMed:34822310). {ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:34822310, ECO:0000269|PubMed:36797247}. |
| P30622 | CLIP1 | T36 | PSP | 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}. |
| P05187 | ALPP | T181 | 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}. |
| P09923 | ALPI | T178 | Sugiyama | Intestinal-type alkaline phosphatase (IAP) (Intestinal alkaline phosphatase) (EC 3.1.3.1) | Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000250|UniProtKB:P15693}. |
| Q86UE4 | MTDH | T326 | Sugiyama | 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}. |
| P10586 | PTPRF | T1846 | Sugiyama | Receptor-type tyrosine-protein phosphatase F (EC 3.1.3.48) (Leukocyte common antigen related) (LAR) | Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity.; FUNCTION: The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. |
| P23468 | PTPRD | T1851 | Sugiyama | Receptor-type tyrosine-protein phosphatase delta (Protein-tyrosine phosphatase delta) (R-PTP-delta) (EC 3.1.3.48) | Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically. Involved in pre-synaptic differentiation through interaction with SLITRK2. {ECO:0000250|UniProtKB:Q64487}. |
| Q13332 | PTPRS | T1887 | Sugiyama | Receptor-type tyrosine-protein phosphatase S (R-PTP-S) (EC 3.1.3.48) (Receptor-type tyrosine-protein phosphatase sigma) (R-PTP-sigma) | Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycan (PubMed:21454754). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth. Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection. Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as a tyrosine phosphatase (PubMed:8524829). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (By similarity). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases (By similarity). Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (PubMed:26231120). {ECO:0000250|UniProtKB:B0V2N1, ECO:0000250|UniProtKB:F1NWE3, ECO:0000269|PubMed:21454754, ECO:0000269|PubMed:26231120, ECO:0000269|PubMed:8524829}. |
| O43175 | PHGDH | T353 | Sugiyama | D-3-phosphoglycerate dehydrogenase (3-PGDH) (EC 1.1.1.95) (2-oxoglutarate reductase) (EC 1.1.1.399) (Malate dehydrogenase) (EC 1.1.1.37) | Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:25406093}. |
| P13639 | EEF2 | T482 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| P14314 | PRKCSH | T448 | 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}. |
| Q9HDC9 | APMAP | T131 | Sugiyama | Adipocyte plasma membrane-associated protein (Protein BSCv) | Exhibits strong arylesterase activity with beta-naphthyl acetate and phenyl acetate. May play a role in adipocyte differentiation. {ECO:0000269|PubMed:18513186}. |
| O43602 | DCX | T293 | Sugiyama | Neuronal migration protein doublecortin (Doublin) (Lissencephalin-X) (Lis-X) | Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration. {ECO:0000269|PubMed:22359282}. |
| Q53H82 | LACTB2 | T97 | Sugiyama | Endoribonuclease LACTB2 (EC 3.1.27.-) (Beta-lactamase-like protein 2) | Endoribonuclease; cleaves preferentially 3' to purine-pyrimidine dinucleotide motifs in single-stranded RNA. The cleavage product contains a free 3' -OH group. Has no activity with double-stranded RNA or DNA. Required for normal mitochondrial function and cell viability. {ECO:0000269|PubMed:26826708}. |
| Q92974 | ARHGEF2 | T802 | Sugiyama | 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}. |
| Q8N5S9 | CAMKK1 | T58 | 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}. |
| P46087 | NOP2 | T409 | Sugiyama | 28S rRNA (cytosine(4447)-C(5))-methyltransferase (EC 2.1.1.-) (Nucleolar protein 1) (Nucleolar protein 2 homolog) (Proliferating-cell nucleolar antigen p120) (Proliferation-associated nucleolar protein p120) | S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA (PubMed:26196125). Required for efficient rRNA processing and 60S ribosomal subunit biogenesis (PubMed:24120868, PubMed:36161484). Regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs and facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes (PubMed:36161484). May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation (PubMed:24120868). {ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:26196125, ECO:0000269|PubMed:36161484}. |
| Q9BYW2 | SETD2 | T1316 | Sugiyama | 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}. |
| Q96PY6 | NEK1 | T431 | 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}. |
| Q99759 | MAP3K3 | T384 | Sugiyama | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q9BZL6 | PRKD2 | T502 | Sugiyama | Serine/threonine-protein kinase D2 (EC 2.7.11.13) (nPKC-D2) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin 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 (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}. |
| Q9H0K1 | SIK2 | T364 | Sugiyama | Serine/threonine-protein kinase SIK2 (EC 2.7.11.1) (Qin-induced kinase) (Salt-inducible kinase 2) (SIK-2) (Serine/threonine-protein kinase SNF1-like kinase 2) | Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:23322770, PubMed:26983400). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity (PubMed:21084751, PubMed:26983400). In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (PubMed:21084751, PubMed:26983400). Also plays a role in thymic T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751, ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}. |
| O75128 | COBL | T1228 | Sugiyama | 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}. |
| Q9H4A3 | WNK1 | T48 | 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}. |
| Q9H4A3 | WNK1 | T51 | 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}. |
| P05556 | ITGB1 | T504 | Sugiyama | Integrin beta-1 (Fibronectin receptor subunit beta) (Glycoprotein IIa) (GPIIA) (VLA-4 subunit beta) (CD antigen CD29) | Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGA4:ITGB1 and ITGA5:ITGB1 bind 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). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1 (PubMed:33962943). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (PubMed:31331973). Plays an important role in myoblast differentiation and fusion during skeletal myogenesis (By similarity). ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion (By similarity). Integrins ITGA9:ITGB1 and ITGA4:ITGB1 repress PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via their interaction with SVEP1, thereby inhibit vasocontraction (PubMed:35802072). {ECO:0000250|UniProtKB:P07228, ECO:0000250|UniProtKB:P09055, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:12473654, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:16256741, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:18804435, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:33962943, ECO:0000269|PubMed:35802072, ECO:0000269|PubMed:7523423}.; FUNCTION: [Isoform 2]: Interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration (in vitro). {ECO:0000305|PubMed:2249781}.; FUNCTION: [Isoform 5]: Isoform 5 displaces isoform 1 in striated muscles. {ECO:0000250|UniProtKB:P09055}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.; FUNCTION: (Microbial infection) Acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:20660204}.; FUNCTION: (Microbial infection) Acts as a receptor for Epstein-Barr virus/HHV-4. {ECO:0000269|PubMed:17945327}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human parvovirus B19. {ECO:0000269|PubMed:12907437}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus. {ECO:0000269|PubMed:12941907}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus. {ECO:0000269|PubMed:16501085}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, integrin ITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.; FUNCTION: (Microbial infection) Interacts with CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:32487760). Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression (PubMed:32487760). {ECO:0000269|PubMed:32487760}.; FUNCTION: (Microbial infection) May serve as a receptor for adhesin A (nadA) of N.meningitidis. {ECO:0000305|PubMed:21471204}.; FUNCTION: (Microbial infection) Facilitates rabies infection in a fibronectin-dependent manner and participates in rabies virus traffic after internalization. {ECO:0000269|PubMed:31666383}. |
| O14641 | DVL2 | T652 | Sugiyama | 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}. |
| P28799 | GRN | T182 | Sugiyama | Progranulin (PGRN) (Acrogranin) (Epithelin precursor) (Glycoprotein of 88 Kda) (GP88) (Glycoprotein 88) (Granulin precursor) (PC cell-derived growth factor) (PCDGF) (Proepithelin) (PEPI) [Cleaved into: Paragranulin; Granulin-1 (Granulin G); Granulin-2 (Granulin F); Granulin-3 (Epithelin-2) (Granulin B); Granulin-4 (Epithelin-1) (Granulin A); Granulin-5 (Granulin C); Granulin-6 (Granulin D); Granulin-7 (Granulin E)] | Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:28073925, PubMed:28453791, PubMed:28541286). Regulates protein trafficking to lysosomes, and also the activity of lysosomal enzymes (PubMed:28453791, PubMed:28541286). Also facilitates the acidification of lysosomes, causing degradation of mature CTSD by CTSB (PubMed:28073925). In addition, functions as a wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures (By similarity). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases (PubMed:12526812). Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity (PubMed:18378771). {ECO:0000250|UniProtKB:P28798, ECO:0000269|PubMed:12526812, ECO:0000269|PubMed:18378771, ECO:0000269|PubMed:28073925, ECO:0000269|PubMed:28453791, ECO:0000269|PubMed:28541286}.; FUNCTION: [Granulin-4]: Promotes proliferation of the epithelial cell line A431 in culture.; FUNCTION: [Granulin-3]: Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8. {ECO:0000269|PubMed:12526812}.; FUNCTION: [Granulin-7]: Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity. {ECO:0000269|PubMed:28453791}. |
| Q9NR20 | DYRK4 | T476 | Sugiyama | Dual specificity tyrosine-phosphorylation-regulated kinase 4 (EC 2.7.12.1) | Possible non-essential role in spermiogenesis. {ECO:0000250}. |
| Q9NYY3 | PLK2 | T103 | Sugiyama | Serine/threonine-protein kinase PLK2 (EC 2.7.11.21) (Polo-like kinase 2) (PLK-2) (hPlk2) (Serine/threonine-protein kinase SNK) (hSNK) (Serum-inducible kinase) | Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CPAP, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CPAP and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress. {ECO:0000269|PubMed:15242618, ECO:0000269|PubMed:19001868, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:20531387}. |
| Q96SQ9 | CYP2S1 | T131 | Sugiyama | Cytochrome P450 2S1 (EC 1.14.14.-) (CYPIIS1) (Hydroperoxy icosatetraenoate dehydratase) (EC 4.2.1.152) (Thromboxane-A synthase) (EC 5.3.99.5) | A cytochrome P450 monooxygenase involved in the metabolism of retinoids and eicosanoids (PubMed:12711469, PubMed:21068195). In epidermis, may contribute to the oxidative metabolism of all-trans-retinoic acid. For this activity, 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:12711469). Additionally, displays peroxidase and isomerase activities toward various oxygenated eicosanoids such as prostaglandin H2 (PGH2) and hydroperoxyeicosatetraenoates (HPETEs) (PubMed:21068195). Independently of cytochrome P450 reductase, NADPH, and O2, catalyzes the breakdown of PGH2 to hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA), which is known to act as a mediator of DNA damage (PubMed:21068195). {ECO:0000269|PubMed:12711469, ECO:0000269|PubMed:21068195}. |
| P47712 | PLA2G4A | T426 | Sugiyama | 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}. |
| Q9UK32 | RPS6KA6 | T718 | 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}. |
| P30086 | PEBP1 | T115 | Sugiyama | 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}. |
| P31153 | MAT2A | T262 | 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}. |
| Q14914 | PTGR1 | T92 | Sugiyama | Prostaglandin reductase 1 (PRG-1) (15-oxoprostaglandin 13-reductase) (EC 1.3.1.48) (Dithiolethione-inducible gene 1 protein) (D3T-inducible gene 1 protein) (DIG-1) (Leukotriene B4 12-hydroxydehydrogenase) (NAD(P)H-dependent alkenal/one oxidoreductase) (EC 1.3.1.74) | NAD(P)H-dependent oxidoreductase involved in metabolic inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins (PG), leukotrienes (LT) and lipoxins (LX) (PubMed:25619643). Catalyzes with high efficiency the reduction of the 13,14 double bond of 15-oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-oxo-PGF2-alpha (PubMed:25619643). Catalyzes with lower efficiency the oxidation of the hydroxyl group at C12 of LTB4 and its derivatives, converting them into biologically less active 12-oxo-LTB4 metabolites (By similarity) (PubMed:25619643). Reduces 15-oxo-LXA4 to 13,14 dihydro-15-oxo-LXA4, enhancing neutrophil recruitment at the inflammatory site (By similarity). May play a role in metabolic detoxification of alkenals and ketones. Reduces alpha,beta-unsaturated alkenals and ketones, particularly those with medium-chain length, showing highest affinity toward (2E)-decenal and (3E)-3-nonen-2-one (PubMed:25619643). May inactivate 4-hydroxy-2-nonenal, a cytotoxic lipid constituent of oxidized low-density lipoprotein particles (By similarity). {ECO:0000250|UniProtKB:P97584, ECO:0000250|UniProtKB:Q29073, ECO:0000269|PubMed:25619643}. |
| Q9Y2U5 | MAP3K2 | T510 | Sugiyama | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| P68104 | EEF1A1 | T279 | Sugiyama | 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}. |
| Q5VTE0 | EEF1A1P5 | T279 | Sugiyama | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q96AY3 | FKBP10 | T441 | 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. |
| Q9Y4K4 | MAP4K5 | T42 | 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}. |
| P62424 | RPL7A | T201 | Sugiyama | Large ribosomal subunit protein eL8 (60S ribosomal protein L7a) (PLA-X polypeptide) (Surfeit locus protein 3) | 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}. |
| P62847 | RPS24 | T70 | Sugiyama | Small ribosomal subunit protein eS24 (40S ribosomal protein S24) | 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 processing of pre-rRNA and maturation of 40S ribosomal subunits (PubMed:18230666). 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:18230666, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| Q99575 | POP1 | T106 | Sugiyama | 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}. |
| A0A0G2JMM0 | LOC128966728 | T118 | ochoa | Uncharacterized protein | None |
| A6NKD9 | CCDC85C | T161 | ochoa | Coiled-coil domain-containing protein 85C | May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family (Probable). May play an important role in cortical development, especially in the maintenance of radial glia (By similarity). {ECO:0000250|UniProtKB:E9Q6B2, ECO:0000305|PubMed:25009281}. |
| A8MSY1 | STIMATE-MUSTN1 | T353 | ochoa | Musculoskeletal embryonic nuclear protein 1 | None |
| E7EW31 | PROB1 | T234 | ochoa | Proline-rich basic protein 1 | None |
| M0QYT0 | None | T204 | ochoa | RRM domain-containing protein | None |
| O00192 | ARVCF | T885 | 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}. |
| O00442 | RTCA | T314 | ochoa | RNA 3'-terminal phosphate cyclase (RNA cyclase) (RNA-3'-phosphate cyclase) (EC 6.5.1.4) (RNA terminal phosphate cyclase domain-containing protein 1) (RTC domain-containing protein 1) | Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA (PubMed:9184239). The mechanism of action of the enzyme occurs in 3 steps: (A) adenylation of the enzyme by ATP; (B) transfer of adenylate to an RNA-N3'P to produce RNA-N3'PP5'A; (C) and attack of the adjacent 2'-hydroxyl on the 3'-phosphorus in the diester linkage to produce the cyclic end product (PubMed:9184239). Likely functions in some aspects of cellular RNA processing (PubMed:25961792, PubMed:9184239). Function plays an important role in regulating axon regeneration by inhibiting central nervous system (CNS) axon regeneration following optic nerve injury (PubMed:25961792). {ECO:0000269|PubMed:25961792, ECO:0000269|PubMed:9184239}. |
| O00571 | DDX3X | T156 | psp | 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}. |
| O14640 | DVL1 | T674 | 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). |
| O14686 | KMT2D | T2650 | 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}. |
| O14744 | PRMT5 | T144 | psp | Protein arginine N-methyltransferase 5 (PRMT5) (EC 2.1.1.320) (72 kDa ICln-binding protein) (Histone-arginine N-methyltransferase PRMT5) (Jak-binding protein 1) (Shk1 kinase-binding protein 1 homolog) (SKB1 homolog) (SKB1Hs) [Cleaved into: Protein arginine N-methyltransferase 5, N-terminally processed] | Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21081503, PubMed:21258366, PubMed:21917714, PubMed:22269951). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:11747828, PubMed:12411503, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). May methylate the N-terminal region of MBD2 (PubMed:16428440). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity). Methylates histone H3 'Arg-8', which may repress transcription (By similarity). Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21258366, PubMed:21917714). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically methylates NCL (PubMed:21081503). Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (PubMed:19011621). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (By similarity). {ECO:0000250|UniProtKB:Q8CIG8, ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:11152681, ECO:0000269|PubMed:11747828, ECO:0000269|PubMed:12411503, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20421892, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805}. |
| O14983 | ATP2A1 | T554 | 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}. |
| O14983 | ATP2A1 | T608 | 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}. |
| O15027 | SEC16A | T1325 | 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 | T526 | 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 | T386 | 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}. |
| O15231 | ZNF185 | T204 | ochoa | Zinc finger protein 185 (LIM domain protein ZNF185) (P1-A) | May be involved in the regulation of cellular proliferation and/or differentiation. |
| O15541 | RNF113A | T323 | ochoa | E3 ubiquitin-protein ligase RNF113A (EC 2.3.2.27) (Cwc24 homolog) (RING finger protein 113A) (Zinc finger protein 183) | Required for pre-mRNA splicing as component of the spliceosome (PubMed:29360106, PubMed:29361316). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin onto target proteins (PubMed:28978524, PubMed:29144457). Catalyzes polyubiquitination of SNRNP200/BRR2 with non-canonical 'Lys-63'-linked polyubiquitin chains (PubMed:29144457). Plays a role in DNA repair via its role in the synthesis of 'Lys-63'-linked polyubiquitin chains that recruit ALKBH3 and the ASCC complex to sites of DNA damage by alkylating agents (PubMed:29144457). Ubiquitinates CXCR4, leading to its degradation, and thereby contributes to the termination of CXCR4 signaling (PubMed:28978524). {ECO:0000269|PubMed:28978524, ECO:0000269|PubMed:29144457, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}. |
| O43175 | PHGDH | T78 | ochoa|psp | D-3-phosphoglycerate dehydrogenase (3-PGDH) (EC 1.1.1.95) (2-oxoglutarate reductase) (EC 1.1.1.399) (Malate dehydrogenase) (EC 1.1.1.37) | Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:25406093}. |
| O43182 | ARHGAP6 | T752 | 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 | T43 | 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}. |
| O60292 | SIPA1L3 | T193 | 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}. |
| O60337 | MARCHF6 | T29 | 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}. |
| O60437 | PPL | T1665 | 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}. |
| O60469 | DSCAM | T276 | ochoa | Cell adhesion molecule DSCAM (CHD2) (Down syndrome cell adhesion molecule) | Cell adhesion molecule that plays a role in neuronal self-avoidance. Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells. Mediates within retinal amacrine and ganglion cell subtypes both isoneuronal self-avoidance for creating an orderly dendritic arborization and heteroneuronal self-avoidance to maintain the mosaic spacing between amacrine and ganglion cell bodies (PubMed:10925149). Receptor for netrin required for axon guidance independently of and in collaboration with the receptor DCC. Might also collaborate with UNC5C in NTN1-mediated axon repulsion independently of DCC (By similarity). In spinal cord development plays a role in guiding commissural axons projection and pathfinding across the ventral midline to reach the floor plate upon ligand binding (PubMed:18585357, PubMed:19196994). Mediates intracellular signaling by stimulating the activation of MAPK8 and MAP kinase p38 (PubMed:18585357, PubMed:19196994). Adhesion molecule that promotes lamina-specific synaptic connections in the retina: expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions (By similarity). {ECO:0000250|UniProtKB:F1NY98, ECO:0000250|UniProtKB:Q9ERC8, ECO:0000269|PubMed:10925149, ECO:0000269|PubMed:18585357, ECO:0000269|PubMed:19196994}. |
| O60716 | CTNND1 | T308 | ochoa|psp | 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}. |
| O75112 | LDB3 | T282 | ochoa | LIM domain-binding protein 3 (Protein cypher) (Z-band alternatively spliced PDZ-motif protein) | May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton. {ECO:0000305}. |
| O75122 | CLASP2 | T594 | 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}. |
| O75376 | NCOR1 | T2378 | 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}. |
| O75469 | NR1I2 | T133 | 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}. |
| O94953 | KDM4B | T571 | ochoa | Lysine-specific demethylase 4B (EC 1.14.11.66) (JmjC domain-containing histone demethylation protein 3B) (Jumonji domain-containing protein 2B) ([histone H3]-trimethyl-L-lysine(9) demethylase 4B) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate (PubMed:16603238, PubMed:28262558). Plays a critical role in the development of the central nervous system (CNS). {ECO:0000250|UniProtKB:Q91VY5, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}. |
| O95218 | ZRANB2 | T100 | ochoa | Zinc finger Ran-binding domain-containing protein 2 (Zinc finger protein 265) (Zinc finger, splicing) | Splice factor required for alternative splicing of TRA2B/SFRS10 transcripts. Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). May interfere with constitutive 5'-splice site selection. {ECO:0000269|PubMed:11448987, ECO:0000269|PubMed:21256132}. |
| O95359 | TACC2 | T2115 | 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}. |
| O95684 | CEP43 | T331 | 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}. |
| P00367 | GLUD1 | T228 | 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}. |
| P00505 | GOT2 | T135 | ochoa | Aspartate aminotransferase, mitochondrial (mAspAT) (EC 2.6.1.1) (EC 2.6.1.7) (Fatty acid-binding protein) (FABP-1) (Glutamate oxaloacetate transaminase 2) (Kynurenine aminotransferase 4) (Kynurenine aminotransferase IV) (Kynurenine--oxoglutarate transaminase 4) (Kynurenine--oxoglutarate transaminase IV) (Plasma membrane-associated fatty acid-binding protein) (FABPpm) (Transaminase A) | Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids. {ECO:0000269|PubMed:31422819, ECO:0000269|PubMed:9537447}. |
| P00533 | EGFR | T1074 | 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}. |
| P02671 | FGA | T279 | 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 | T543 | 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 | T37 | 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}. |
| P04792 | HSPB1 | T121 | 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 | T261 | 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}. |
| P05091 | ALDH2 | T202 | psp | Aldehyde dehydrogenase, mitochondrial (EC 1.2.1.3) (ALDH class 2) (ALDH-E2) (ALDHI) | Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. {ECO:0000269|PubMed:33355142}. |
| P05181 | CYP2E1 | T432 | 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}. |
| P05556 | ITGB1 | T777 | ochoa | Integrin beta-1 (Fibronectin receptor subunit beta) (Glycoprotein IIa) (GPIIA) (VLA-4 subunit beta) (CD antigen CD29) | Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGA4:ITGB1 and ITGA5:ITGB1 bind 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). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1 (PubMed:33962943). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (PubMed:31331973). Plays an important role in myoblast differentiation and fusion during skeletal myogenesis (By similarity). ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion (By similarity). Integrins ITGA9:ITGB1 and ITGA4:ITGB1 repress PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via their interaction with SVEP1, thereby inhibit vasocontraction (PubMed:35802072). {ECO:0000250|UniProtKB:P07228, ECO:0000250|UniProtKB:P09055, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:12473654, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:16256741, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:18804435, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:33962943, ECO:0000269|PubMed:35802072, ECO:0000269|PubMed:7523423}.; FUNCTION: [Isoform 2]: Interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration (in vitro). {ECO:0000305|PubMed:2249781}.; FUNCTION: [Isoform 5]: Isoform 5 displaces isoform 1 in striated muscles. {ECO:0000250|UniProtKB:P09055}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.; FUNCTION: (Microbial infection) Acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:20660204}.; FUNCTION: (Microbial infection) Acts as a receptor for Epstein-Barr virus/HHV-4. {ECO:0000269|PubMed:17945327}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human parvovirus B19. {ECO:0000269|PubMed:12907437}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus. {ECO:0000269|PubMed:12941907}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus. {ECO:0000269|PubMed:16501085}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, integrin ITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.; FUNCTION: (Microbial infection) Interacts with CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:32487760). Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression (PubMed:32487760). {ECO:0000269|PubMed:32487760}.; FUNCTION: (Microbial infection) May serve as a receptor for adhesin A (nadA) of N.meningitidis. {ECO:0000305|PubMed:21471204}.; FUNCTION: (Microbial infection) Facilitates rabies infection in a fibronectin-dependent manner and participates in rabies virus traffic after internalization. {ECO:0000269|PubMed:31666383}. |
| P05783 | KRT18 | T65 | ochoa | Keratin, type I cytoskeletal 18 (Cell proliferation-inducing gene 46 protein) (Cytokeratin-18) (CK-18) (Keratin-18) (K18) | Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection. {ECO:0000250, ECO:0000269|PubMed:15529338, ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:7523419, ECO:0000269|PubMed:8522591, ECO:0000269|PubMed:9298992, ECO:0000269|PubMed:9524113}. |
| P06732 | CKM | T322 | 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}. |
| P07900 | HSP90AA1 | T495 | 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}. |
| P07996 | THBS1 | T625 | 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}. |
| P08240 | SRPRA | T284 | 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}. |
| P08590 | MYL3 | T127 | ochoa | Myosin light chain 3 (Cardiac myosin light chain 1) (CMLC1) (Myosin light chain 1, slow-twitch muscle B/ventricular isoform) (MLC1SB) (Ventricular myosin alkali light chain) (Ventricular myosin light chain 1) (VLCl) (Ventricular/slow twitch myosin alkali light chain) (MLC-lV/sb) | Regulatory light chain of myosin. Does not bind calcium. |
| P09622 | DLD | T135 | psp | Dihydrolipoyl dehydrogenase, mitochondrial (EC 1.8.1.4) (Dihydrolipoamide dehydrogenase) (Glycine cleavage system L protein) | Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity). {ECO:0000250|UniProtKB:Q811C4, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:20385101, ECO:0000269|PubMed:29211711}. |
| P0DJ93 | SMIM13 | T48 | ochoa | Small integral membrane protein 13 | None |
| P0DPH7 | TUBA3C | T94 | 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 | T94 | 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. |
| P12277 | CKB | T322 | ochoa | Creatine kinase B-type (EC 2.7.3.2) (Brain creatine kinase) (B-CK) (Creatine kinase B chain) (Creatine phosphokinase B-type) (CPK-B) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). 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 (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity). {ECO:0000250|UniProtKB:Q04447, ECO:0000269|PubMed:8186255, ECO:0000305}. |
| P12956 | XRCC6 | T307 | 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}. |
| P14618 | PKM | T45 | 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 | T121 | 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 | T396 | 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}. |
| P15259 | PGAM2 | T96 | ochoa | Phosphoglycerate mutase 2 (EC 5.4.2.11) (EC 5.4.2.4) (BPG-dependent PGAM 2) (Muscle-specific phosphoglycerate mutase) (Phosphoglycerate mutase isozyme M) (PGAM-M) | Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase), but with a reduced activity. |
| P15880 | RPS2 | T202 | 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 | T59 | 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 | T2524 | 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}. |
| P17540 | CKMT2 | T323 | ochoa | Creatine kinase S-type, mitochondrial (EC 2.7.3.2) (Basic-type mitochondrial creatine kinase) (Mib-CK) (Sarcomeric mitochondrial creatine kinase) (S-MtCK) | 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. |
| P17540 | CKMT2 | T356 | ochoa | Creatine kinase S-type, mitochondrial (EC 2.7.3.2) (Basic-type mitochondrial creatine kinase) (Mib-CK) (Sarcomeric mitochondrial creatine kinase) (S-MtCK) | 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. |
| P17612 | PRKACA | T52 | 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}. |
| P17844 | DDX5 | T564 | psp | 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 | T1596 | 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}. |
| P18669 | PGAM1 | T96 | ochoa | Phosphoglycerate mutase 1 (EC 5.4.2.11) (EC 5.4.2.4) (BPG-dependent PGAM 1) (Phosphoglycerate mutase isozyme B) (PGAM-B) | Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate (PubMed:23653202). Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate (PubMed:23653202). {ECO:0000269|PubMed:23653202}. |
| P19338 | NCL | T325 | ochoa | 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}. |
| P20290 | BTF3 | T182 | 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}. |
| P21333 | FLNA | T1288 | 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}. |
| P22059 | OSBP | T377 | 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}. |
| P23528 | CFL1 | T129 | ochoa | Cofilin-1 (18 kDa phosphoprotein) (p18) (Cofilin, non-muscle isoform) | Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity (PubMed:11812157). In conjunction with the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:15580268). Required for the centralization of the mitotic spindle and symmetric division of zygotes (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization in epithelial cells (PubMed:21834987). Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). Required for neural tube morphogenesis and neural crest cell migration (By similarity). {ECO:0000250|UniProtKB:P18760, ECO:0000269|PubMed:11812157, ECO:0000269|PubMed:15580268, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:23633677}. |
| P25490 | YY1 | T256 | ochoa | Transcriptional repressor protein YY1 (Delta transcription factor) (INO80 complex subunit S) (NF-E1) (Yin and yang 1) (YY-1) | Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site (PubMed:15329343, PubMed:17721549, PubMed:24326773, PubMed:25787250). Binds to the consensus sequence 5'-CCGCCATNTT-3'; some genes have been shown to contain a longer binding motif allowing enhanced binding; the initial CG dinucleotide can be methylated greatly reducing the binding affinity (PubMed:15329343, PubMed:17721549, PubMed:24326773, PubMed:25787250). The effect on transcription regulation is depending upon the context in which it binds and diverse mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes (PubMed:15329343, PubMed:17721549, PubMed:24326773, PubMed:25787250). Its activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression (PubMed:15329343, PubMed:17721549, PubMed:24326773, PubMed:25787250). For example, it acts as a repressor in absence of adenovirus E1A protein but as an activator in its presence (PubMed:1655281). Acts synergistically with the SMAD1 and SMAD4 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343). Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (PubMed:15329343). May play an important role in development and differentiation. Proposed to recruit the PRC2/EED-EZH2 complex to target genes that are transcriptional repressed (PubMed:11158321). Involved in DNA repair (PubMed:18026119, PubMed:28575647). In vitro, binds to DNA recombination intermediate structures (Holliday junctions). Plays a role in regulating enhancer activation (PubMed:28575647). Recruits the PR-DUB complex to specific gene-regulatory regions (PubMed:20805357). {ECO:0000269|PubMed:11158321, ECO:0000269|PubMed:15329343, ECO:0000269|PubMed:1655281, ECO:0000269|PubMed:17721549, ECO:0000269|PubMed:18026119, ECO:0000269|PubMed:20805357, ECO:0000269|PubMed:24326773, ECO:0000269|PubMed:25787250, ECO:0000269|PubMed:28575647}.; FUNCTION: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair; proposed to target the INO80 complex to YY1-responsive elements. {ECO:0000269|PubMed:17721549, ECO:0000269|PubMed:18026119}. |
| P25705 | ATP5F1A | T134 | 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}. |
| P28072 | PSMB6 | T56 | 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}. |
| P28290 | ITPRID2 | T1163 | 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 |
| P29728 | OAS2 | T405 | 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}. |
| P30273 | FCER1G | T66 | ochoa | High affinity immunoglobulin epsilon receptor subunit gamma (Fc receptor gamma-chain) (FcRgamma) (Fc-epsilon RI-gamma) (IgE Fc receptor subunit gamma) (FceRI gamma) | Adapter protein containing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. As a component of the high-affinity immunoglobulin E (IgE) receptor, mediates allergic inflammatory signaling in mast cells. As a constitutive component of interleukin-3 receptor complex, selectively mediates interleukin 4/IL4 production by basophils, priming T-cells toward effector T-helper 2 subset. Associates with pattern recognition receptors CLEC4D and CLEC4E to form a functional signaling complex in myeloid cells. Binding of mycobacterial trehalose 6,6'-dimycolate (TDM) to this receptor complex leads to phosphorylation of ITAM, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes. May function cooperatively with other activating receptors. Functionally linked to integrin beta-2/ITGB2-mediated neutrophil activation. Also involved in integrin alpha-2/ITGA2-mediated platelet activation. {ECO:0000250|UniProtKB:P20491}. |
| P30414 | NKTR | T1208 | 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 | T106 | 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}. |
| P34897 | SHMT2 | T44 | 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}. |
| P35251 | RFC1 | T171 | 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}. |
| P35462 | DRD3 | T142 | psp | D(3) dopamine receptor (Dopamine D3 receptor) | Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation. {ECO:0000269|PubMed:19520868}. |
| P35968 | KDR | T799 | ochoa | Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}. |
| P36871 | PGM1 | T507 | 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}. |
| P40337 | VHL | T105 | psp | von Hippel-Lindau disease tumor suppressor (Protein G7) (pVHL) | Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions (PubMed:10944113, PubMed:17981124). Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases (PubMed:10944113, PubMed:17981124). Ubiquitinates, in an oxygen-responsive manner, ADRB2 (PubMed:19584355). Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR (PubMed:34290272). {ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:34290272}. |
| P42224 | STAT1 | T699 | ochoa | Signal transducer and activator of transcription 1-alpha/beta (Transcription factor ISGF-3 components p91/p84) | Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity). {ECO:0000250|UniProtKB:P42225, ECO:0000269|PubMed:12764129, ECO:0000269|PubMed:12855578, ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:23940278, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:34508746, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:8156998, ECO:0000269|PubMed:9724754, ECO:0000303|PubMed:15526160}. |
| P46013 | MKI67 | T369 | 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 | T1327 | 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 | T1347 | 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 | T1449 | 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}. |
| P46937 | YAP1 | T145 | ochoa | Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog) | Transcriptional regulator with dual roles as a coactivator and corepressor. Critical downstream regulatory target in the Hippo signaling pathway, crucial for organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The Hippo signaling pathway core involves a kinase cascade featuring STK3/MST2 and STK4/MST1, along with its regulatory partner SAV1, which phosphorylates and activates LATS1/2 in complex with their regulatory protein, MOB1. This activation leads to the phosphorylation and inactivation of the YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Phosphorylation of YAP1 by LATS1/2 prevents its nuclear translocation, thereby regulating the expression of its target genes (PubMed:18158288, PubMed:26598551, PubMed:34404733). The transcriptional regulation of gene expression requires TEAD transcription factors and modulates cell growth, anchorage-independent growth, and induction of epithelial-mesenchymal transition (EMT) (PubMed:18579750). Plays a key role in tissue tension and 3D tissue shape by regulating the cortical actomyosin network, acting via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). It also suppresses ciliogenesis by acting as a transcriptional corepressor of TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, regulates TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). Synergizes with WBP2 to enhance PGR activity (PubMed:16772533). {ECO:0000250|UniProtKB:P46938, ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:25778702, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:30447097, ECO:0000269|PubMed:34404733}.; FUNCTION: [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.; FUNCTION: [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}. |
| P48549 | KCNJ3 | T407 | psp | G protein-activated inward rectifier potassium channel 1 (GIRK-1) (Inward rectifier K(+) channel Kir3.1) (Potassium channel, inwardly rectifying subfamily J member 3) | Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This potassium channel is controlled by G proteins (PubMed:8804710, PubMed:8868049). This receptor plays a crucial role in regulating the heartbeat (By similarity). {ECO:0000250|UniProtKB:P63251, ECO:0000269|PubMed:8804710, ECO:0000269|PubMed:8868049}. |
| P48634 | PRRC2A | T894 | 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 | T1108 | 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}. |
| P48730 | CSNK1D | T174 | psp | Casein kinase I isoform delta (CKI-delta) (CKId) (EC 2.7.11.1) (Tau-protein kinase CSNK1D) (EC 2.7.11.26) | Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (By similarity). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. {ECO:0000250|UniProtKB:Q9DC28, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:16027726, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:19043076, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:20407760, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:20696890, ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:21084295, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092}. |
| P49189 | ALDH9A1 | T236 | 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}. |
| P49674 | CSNK1E | T334 | 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}. |
| P50851 | LRBA | T1566 | 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 | T293 | psp | 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}. |
| P51587 | BRCA2 | T3211 | 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}. |
| P52209 | PGD | T166 | ochoa | 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}. |
| P54278 | PMS2 | T511 | 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}. |
| P54792 | DVL1P1 | T649 | ochoa | Putative segment polarity protein dishevelled homolog DVL1P1 (DSH homolog 1-like) (Segment polarity protein dishevelled homolog DVL-1-like) (Dishevelled-1-like) | May play a role in the signal transduction pathway mediated by multiple Wnt genes. |
| P55317 | FOXA1 | T343 | ochoa | Hepatocyte nuclear factor 3-alpha (HNF-3-alpha) (HNF-3A) (Forkhead box protein A1) (Transcription factor 3A) (TCF-3A) | Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in estrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles (By similarity). Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription; required for ESR1 binding to the NKX2-1 promoter in breast cancer cells; binds to the RPRM promoter and is required for the estrogen-induced repression of RPRM. Involved in regulation of apoptosis by inhibiting the expression of BCL2. Involved in cell cycle regulation by activating expression of CDKN1B, alone or in conjunction with BRCA1. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis. {ECO:0000250, ECO:0000269|PubMed:16087863, ECO:0000269|PubMed:16331276, ECO:0000269|PubMed:18358809, ECO:0000269|PubMed:19127412, ECO:0000269|PubMed:19917725}. |
| P56373 | P2RX3 | T134 | psp | P2X purinoceptor 3 (P2X3) (ATP receptor) (Purinergic receptor) | Extracellular ATP-activated non-selective cation channel (PubMed:10440098, PubMed:27626375, PubMed:29674445, PubMed:31232692). Plays particularly important role in sensory neurons where its activation is critical for gustatory, nociceptive responses, visceral reflexes and sensory hypersensitization (By similarity). {ECO:0000250|UniProtKB:Q3UR32, ECO:0000269|PubMed:10440098, ECO:0000269|PubMed:27626375, ECO:0000269|PubMed:29674445, ECO:0000269|PubMed:31232692}. |
| P61371 | ISL1 | T261 | ochoa | Insulin gene enhancer protein ISL-1 (Islet-1) | DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1 (By similarity). Binds to insulin gene enhancer sequences (By similarity). Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity). {ECO:0000250|UniProtKB:P61372, ECO:0000250|UniProtKB:P61374}. |
| P61978 | HNRNPK | T438 | 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}. |
| P62280 | RPS11 | T28 | psp | Small ribosomal subunit protein uS17 (40S ribosomal protein S11) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. 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}. |
| P63244 | RACK1 | T192 | psp | Small ribosomal subunit protein RACK1 (Cell proliferation-inducing gene 21 protein) (Guanine nucleotide-binding protein subunit beta-2-like 1) (Guanine nucleotide-binding protein subunit beta-like protein 12.3) (Human lung cancer oncogene 7 protein) (HLC-7) (Receptor for activated C kinase) (Receptor of activated protein C kinase 1) [Cleaved into: Small ribosomal subunit protein RACK1, N-terminally processed (Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed) (Receptor of activated protein C kinase 1, N-terminally processed)] | Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843). Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (PubMed:19674157). Promotes migration of breast carcinoma cells by binding to and activating RHOA (PubMed:20499158). Acts as an adapter for the dephosphorylation and inactivation of AKT1 by promoting recruitment of PP2A phosphatase to AKT1 (By similarity). {ECO:0000250|UniProtKB:P68040, ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:12589061, ECO:0000269|PubMed:12958311, ECO:0000269|PubMed:17108144, ECO:0000269|PubMed:17244529, ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:18088317, ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18621736, ECO:0000269|PubMed:19423701, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:19785988, ECO:0000269|PubMed:20499158, ECO:0000269|PubMed:20541605, ECO:0000269|PubMed:20573744, ECO:0000269|PubMed:20976005, ECO:0000269|PubMed:21212275, ECO:0000269|PubMed:21347310, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:28132843, ECO:0000269|PubMed:9584165}.; FUNCTION: (Microbial infection) Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells. {ECO:0000269|PubMed:21347310}.; FUNCTION: (Microbial infection) Enhances phosphorylation of HIV-1 Nef by PKCs. {ECO:0000269|PubMed:11312657}.; FUNCTION: (Microbial infection) In case of poxvirus infection, remodels the ribosomes so that they become optimal for the viral mRNAs (containing poly-A leaders) translation but not for host mRNAs. {ECO:0000269|PubMed:28636603}.; FUNCTION: (Microbial infection) Contributes to the cap-independent internal ribosome entry site (IRES)-mediated translation by some RNA viruses. {ECO:0000269|PubMed:25416947}. |
| P68363 | TUBA1B | T94 | 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 | T94 | 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. |
| P78314 | SH3BP2 | T439 | ochoa | SH3 domain-binding protein 2 (3BP-2) | Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism. |
| P78344 | EIF4G2 | T385 | 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 | T516 | 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}. |
| Q00610 | CLTC | T238 | ochoa | 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}. |
| Q02241 | KIF23 | T123 | 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}. |
| Q03164 | KMT2A | T2652 | 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}. |
| Q05397 | PTK2 | T24 | 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}. |
| Q08J23 | NSUN2 | T479 | ochoa | RNA cytosine C(5)-methyltransferase NSUN2 (EC 2.1.1.-) (Myc-induced SUN domain-containing protein) (Misu) (NOL1/NOP2/Sun domain family member 2) (Substrate of AIM1/Aurora kinase B) (mRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (tRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-, EC 2.1.1.203) (tRNA methyltransferase 4 homolog) (hTrm4) | RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847). {ECO:0000250|UniProtKB:Q1HFZ0, ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:22995836, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31199786, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:34556860}. |
| Q09666 | AHNAK | T457 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T553 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T1885 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T2147 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | T2845 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12802 | AKAP13 | T866 | 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}. |
| Q12888 | TP53BP1 | T1012 | 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 | T1370 | 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}. |
| Q12906 | ILF3 | T469 | ochoa | Interleukin enhancer-binding factor 3 (Double-stranded RNA-binding protein 76) (DRBP76) (M-phase phosphoprotein 4) (MPP4) (Nuclear factor associated with dsRNA) (NFAR) (Nuclear factor of activated T-cells 90 kDa) (NF-AT-90) (Translational control protein 80) (TCP80) | RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651, PubMed:34110282). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552). {ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:28625552, ECO:0000269|PubMed:9442054}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3. {ECO:0000269|PubMed:26891316}. |
| Q13011 | ECH1 | T34 | 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}. |
| Q13206 | DDX10 | T717 | ochoa | Probable ATP-dependent RNA helicase DDX10 (EC 3.6.4.13) (DEAD box protein 10) | Putative ATP-dependent RNA helicase that plays various role in innate immunity or inflammation. Plays a role in the enhancement of AIM2-induced inflammasome activation by interacting with AIM2 and stabilizing its protein level (PubMed:32519665). Negatively regulates viral infection by promoting interferon beta production and interferon stimulated genes/ISGs expression (PubMed:36779599). {ECO:0000269|PubMed:32519665, ECO:0000269|PubMed:36779599}. |
| Q13330 | MTA1 | T380 | ochoa | Metastasis-associated protein MTA1 | Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator (PubMed:16617102, PubMed:17671180, PubMed:17922032, PubMed:21965678, PubMed:24413532). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). In the NuRD complex, regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA (PubMed:17671180). In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A (PubMed:17922032, PubMed:24413532). Acts as a transcriptional coactivator of BCAS3, and SUMO2, independent of the NuRD complex (PubMed:16617102, PubMed:17671180, PubMed:21965678). Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3 (By similarity). Regulates p53-dependent and -independent DNA repair processes following genotoxic stress (PubMed:19837670). Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair (PubMed:19837670). Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles (By similarity). Positively regulates the CLOCK-BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1 (By similarity). Regulates deacetylation of BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression (By similarity). With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation (By similarity). {ECO:0000250|UniProtKB:Q8K4B0, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:17671180, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24413532}.; FUNCTION: [Isoform Short]: Binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. {ECO:0000269|PubMed:15077195}. |
| Q13393 | PLD1 | T624 | 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}. |
| Q13561 | DCTN2 | T196 | ochoa | Dynactin subunit 2 (50 kDa dynein-associated polypeptide) (Dynactin complex 50 kDa subunit) (DCTN-50) (p50 dynamitin) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (By similarity). {ECO:0000250|UniProtKB:A0A5G2QD80, ECO:0000250|UniProtKB:Q99KJ8}. |
| Q13621 | SLC12A1 | T118 | 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}. |
| Q14008 | CKAP5 | T569 | 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}. |
| Q14157 | UBAP2L | T358 | 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}. |
| Q14157 | UBAP2L | T847 | 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}. |
| Q14315 | FLNC | T1283 | 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 | T2129 | 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 | T2593 | 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}. |
| Q14324 | MYBPC2 | T468 | ochoa | Myosin-binding protein C, fast-type (Fast MyBP-C) (C-protein, skeletal muscle fast isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. |
| Q14457 | BECN1 | T406 | 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}. |
| Q14511 | NEDD9 | T122 | 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}. |
| Q14980 | NUMA1 | T1958 | 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}. |
| Q15149 | PLEC | T4646 | 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}. |
| Q15637 | SF1 | T67 | ochoa | Splicing factor 1 (Mammalian branch point-binding protein) (BBP) (mBBP) (Transcription factor ZFM1) (Zinc finger gene in MEN1 locus) (Zinc finger protein 162) | Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor. {ECO:0000269|PubMed:10449420, ECO:0000269|PubMed:8752089, ECO:0000269|PubMed:9660765}. |
| Q16531 | DDB1 | T118 | ochoa | DNA damage-binding protein 1 (DDB p127 subunit) (DNA damage-binding protein a) (DDBa) (Damage-specific DNA-binding protein 1) (HBV X-associated protein 1) (XAP-1) (UV-damaged DNA-binding factor) (UV-damaged DNA-binding protein 1) (UV-DDB 1) (XPE-binding factor) (XPE-BF) (Xeroderma pigmentosum group E-complementing protein) (XPCe) | Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:14739464, PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16407252, PubMed:16482215, PubMed:16940174, PubMed:17079684). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:25043012, PubMed:25108355, PubMed:28886238). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:25043012, PubMed:25108355). DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (PubMed:16473935, PubMed:16678110, PubMed:17041588, PubMed:18593899). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (PubMed:16473935, PubMed:16678110, PubMed:17041588, PubMed:18593899). DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (PubMed:15882621). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:17041588). DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR) (PubMed:12732143, PubMed:32355176, PubMed:38316879). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver (By similarity). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (By similarity). Maternal factor required for proper zygotic genome activation and genome reprogramming (By similarity). {ECO:0000250|UniProtKB:Q3U1J4, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:16260596, ECO:0000269|PubMed:16407242, ECO:0000269|PubMed:16407252, ECO:0000269|PubMed:16473935, ECO:0000269|PubMed:16482215, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16940174, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:17079684, ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18381890, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19966799, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:25043012, ECO:0000269|PubMed:25108355, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:28886238, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:38316879}. |
| Q17R98 | ZNF827 | T953 | 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}. |
| Q29RF7 | PDS5A | T1160 | 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}. |
| Q2KHR3 | QSER1 | T1278 | ochoa | Glutamine and serine-rich protein 1 | Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation. {ECO:0000269|PubMed:33833093}. |
| Q2LD37 | BLTP1 | T2298 | 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 | T385 | 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 | T805 | 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}. |
| Q5SYE7 | NHSL1 | T380 | ochoa | NHS-like protein 1 | None |
| Q5T0W9 | FAM83B | T561 | 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}. |
| Q5T1M5 | FKBP15 | T1132 | 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}. |
| Q5T447 | HECTD3 | T84 | psp | E3 ubiquitin-protein ligase HECTD3 (EC 2.3.2.26) (HECT domain-containing protein 3) (HECT-type E3 ubiquitin transferase HECTD3) | E3 ubiquitin ligases accepts 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 TRIOBP and its subsequent proteasomal degradation, thus facilitating cell cycle progression by regulating the turn-over of TRIOBP. Mediates also ubiquitination of STX8 (By similarity). {ECO:0000250|UniProtKB:Q3U487, ECO:0000269|PubMed:18194665}. |
| Q5T4S7 | UBR4 | T360 | 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}. |
| Q5TH69 | ARFGEF3 | T1047 | 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}. |
| Q5VZ89 | DENND4C | T1212 | 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}. |
| Q641Q2 | WASHC2A | T448 | 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 | T1140 | 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}. |
| Q68DN1 | SPATA31H1 | T186 | ochoa | Spermatogenesis-associated protein 31H1 | None |
| Q6AI39 | BICRAL | T604 | ochoa | BRD4-interacting chromatin-remodeling complex-associated protein-like (Glioma tumor suppressor candidate region gene 1 protein-like) | Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. {ECO:0000269|PubMed:29374058}. |
| Q6NUP7 | PPP4R4 | T147 | ochoa | Serine/threonine-protein phosphatase 4 regulatory subunit 4 | Putative regulatory subunit of serine/threonine-protein phosphatase 4. |
| Q6R327 | RICTOR | T1172 | 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 | T1472 | 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}. |
| Q6UX73 | C16orf89 | T169 | ochoa | UPF0764 protein C16orf89 | None |
| Q6WCQ1 | MPRIP | T889 | 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 | T1169 | 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}. |
| Q71U36 | TUBA1A | T94 | 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. |
| Q7LBC6 | KDM3B | T1311 | 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}. |
| Q7Z3C6 | ATG9A | T673 | 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}. |
| Q7Z4F1 | LRP10 | T596 | ochoa | Low-density lipoprotein receptor-related protein 10 (LRP-10) | Probable receptor, which is involved in the internalization of lipophilic molecules and/or signal transduction. May be involved in the uptake of lipoprotein APOE in liver (By similarity). {ECO:0000250}. |
| Q7Z6B7 | SRGAP1 | T945 | 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}. |
| Q86TV6 | TTC7B | T655 | 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}. |
| Q86UU1 | PHLDB1 | T1015 | ochoa | Pleckstrin homology-like domain family B member 1 (Protein LL5-alpha) | None |
| Q86UX7 | FERMT3 | T482 | 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}. |
| Q86VQ1 | GLCCI1 | T177 | ochoa | Glucocorticoid-induced transcript 1 protein | None |
| Q86WB0 | ZC3HC1 | T384 | ochoa | Zinc finger C3HC-type protein 1 (Nuclear-interacting partner of ALK) (hNIPA) (Nuclear-interacting partner of anaplastic lymphoma kinase) | Required for proper positioning of a substantial amount of TPR at the nuclear basket (NB) through interaction with TPR. {ECO:0000269|PubMed:34440706}. |
| Q86WV6 | STING1 | T229 | ochoa | Stimulator of interferon genes protein (hSTING) (Endoplasmic reticulum interferon stimulator) (ERIS) (Mediator of IRF3 activation) (hMITA) (Transmembrane protein 173) | Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23747010, PubMed:23910378, PubMed:27801882, PubMed:29973723, PubMed:30842659, PubMed:35045565, PubMed:35388221, PubMed:36808561, PubMed:37832545, PubMed:25704810, PubMed:39255680). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:23747010, PubMed:23910378, PubMed:26229117, PubMed:30842659, PubMed:35388221, PubMed:37379839). Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state (PubMed:22394562, PubMed:25636800, PubMed:29973723, PubMed:30842653, PubMed:35045565, PubMed:35388221). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:23747010, PubMed:23910378, PubMed:26300263). The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation (PubMed:26150511). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (PubMed:30842662). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (PubMed:30842662). Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation (PubMed:37535724). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (PubMed:18724357). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23747010, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:26150511, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:36808561, ECO:0000269|PubMed:37379839, ECO:0000269|PubMed:37535724, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:39255680}.; FUNCTION: (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230). {ECO:0000269|PubMed:26405230}. |
| Q8IU81 | IRF2BP1 | T493 | 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}. |
| Q8IUC4 | RHPN2 | T31 | ochoa | Rhophilin-2 (76 kDa RhoB effector protein) (GTP-Rho-binding protein 2) (p76RBE) | Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity. {ECO:0000269|PubMed:12221077}. |
| Q8IVF2 | AHNAK2 | T330 | ochoa | Protein AHNAK2 | None |
| Q8IVN3 | MUSTN1 | T63 | ochoa | Musculoskeletal embryonic nuclear protein 1 | Required for chondrocyte development and proliferation. Plays a role in myoblast differentiation and fusion. Modulates skeletal muscle extracellular matrix composition. Plays a role in skeletal muscle function. Plays a role in glucose homeostasis. {ECO:0000250|UniProtKB:Q99JI1}. |
| Q8IWZ8 | SUGP1 | T132 | ochoa | SURP and G-patch domain-containing protein 1 (RNA-binding protein RBP) (Splicing factor 4) | Plays a role in pre-mRNA splicing. |
| Q8IZD4 | DCP1B | T142 | ochoa | mRNA-decapping enzyme 1B (EC 3.6.1.62) | May play a role in the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. May remove the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (By similarity). {ECO:0000250|UniProtKB:Q9NPI6}. |
| Q8N0Y7 | PGAM4 | T96 | ochoa | Probable phosphoglycerate mutase 4 (EC 5.4.2.11) (EC 5.4.2.4) | None |
| Q8N183 | NDUFAF2 | T150 | ochoa | NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2 (B17.2-like) (B17.2L) (Mimitin) (Myc-induced mitochondrial protein) (MMTN) (NDUFA12-like protein) | Acts as a molecular chaperone for mitochondrial complex I assembly (PubMed:16200211, PubMed:19384974). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:16200211, PubMed:27626371). Is involved in the initial steps of cilia formation, including removal of CP110 from the mother centrioles, docking of membrane vesicles to the mother centrioles, and establishment of the transition zone (PubMed:38949024). {ECO:0000269|PubMed:16200211, ECO:0000269|PubMed:19384974, ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:38949024}. |
| Q8N3X1 | FNBP4 | T104 | ochoa | Formin-binding protein 4 (Formin-binding protein 30) | None |
| Q8N573 | OXR1 | T389 | ochoa | Oxidation resistance protein 1 | May be involved in protection from oxidative damage. {ECO:0000269|PubMed:11114193, ECO:0000269|PubMed:15060142}. |
| Q8N5D0 | WDTC1 | T652 | ochoa | WD and tetratricopeptide repeats protein 1 | May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:16964240}. |
| Q8N8Z6 | DCBLD1 | T548 | ochoa | Discoidin, CUB and LCCL domain-containing protein 1 | None |
| Q8NEL9 | DDHD1 | T242 | ochoa | Phospholipase DDHD1 (EC 3.1.1.111) (EC 3.1.1.32) (DDHD domain-containing protein 1) (Phosphatidic acid-preferring phospholipase A1 homolog) (PA-PLA1) (EC 3.1.1.118) (Phospholipid sn-1 acylhydrolase) | Phospholipase A1 (PLA1) that hydrolyzes ester bonds at the sn-1 position of glycerophospholipids producing a free fatty acid and a lysophospholipid (Probable) (PubMed:20359546, PubMed:22922100). Prefers phosphatidate (1,2-diacyl-sn-glycero-3-phosphate, PA) as substrate in vitro, but can efficiently hydrolyze phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI), as well as a range of other glycerophospholipid substrates such as phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE), phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) and phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol), PG) (Probable) (PubMed:20359546). Involved in the regulation of the endogenous content of polyunsaturated PI and PS lipids in the nervous system. Changes in these lipids extend to downstream metabolic products like PI phosphates PIP and PIP2, which play fundamental roles in cell biology (By similarity). Regulates mitochondrial morphology (PubMed:24599962). These dynamic changes may be due to PA hydrolysis at the mitochondrial surface (PubMed:24599962). May play a regulatory role in spermatogenesis or sperm function (PubMed:24599962). {ECO:0000250|UniProtKB:Q80YA3, ECO:0000269|PubMed:20359546, ECO:0000269|PubMed:22922100, ECO:0000269|PubMed:24599962, ECO:0000303|PubMed:24599962, ECO:0000305|PubMed:37189713}. |
| Q8NEV4 | MYO3A | T908 | psp | Myosin-IIIa (EC 2.7.11.1) | Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:29880844, PubMed:34788109). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315, ECO:0000269|PubMed:29880844, ECO:0000269|PubMed:34788109}. |
| Q8TBA6 | GOLGA5 | T56 | 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}. |
| Q8TES7 | FBF1 | T509 | ochoa | Fas-binding factor 1 (FBF-1) (Protein albatross) | Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis. {ECO:0000269|PubMed:18838552, ECO:0000269|PubMed:23348840}. |
| Q8TEW8 | PARD3B | T1019 | ochoa | Partitioning defective 3 homolog B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 19 protein) (PAR3-beta) (Partitioning defective 3-like protein) (PAR3-L protein) | Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. |
| Q8TF01 | PNISR | T383 | 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 | T167 | 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}. |
| Q8TF76 | HASPIN | T289 | ochoa|psp | Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) | Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}. |
| Q8WU90 | ZC3H15 | T318 | ochoa | Zinc finger CCCH domain-containing protein 15 (DRG family-regulatory protein 1) (Likely ortholog of mouse immediate early response erythropoietin 4) | Protects DRG1 from proteolytic degradation (PubMed:19819225). Stimulates DRG1 GTPase activity likely by increasing the affinity for the potassium ions (PubMed:23711155). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155}. |
| Q92508 | PIEZO1 | T389 | ochoa | Piezo-type mechanosensitive ion channel component 1 (Membrane protein induced by beta-amyloid treatment) (Mib) (Protein FAM38A) | 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:23479567, PubMed:23695678, PubMed:25955826, 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). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium (By similarity). Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+) (PubMed:25955826). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents (PubMed:25955826). Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling (PubMed:20016066). 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). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing (By similarity). Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells (By similarity). In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007). {ECO:0000250|UniProtKB:E2JF22, ECO:0000250|UniProtKB:Q91X60, ECO:0000269|PubMed:25955826, ECO:0000269|PubMed:29799007}. |
| Q92558 | WASF1 | T301 | ochoa | Actin-binding protein WASF1 (Protein WAVE-1) (Verprolin homology domain-containing protein 1) (Wiskott-Aldrich syndrome protein family member 1) (WASP family protein member 1) | Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation (PubMed:29961568). The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). Also involved in the regulation of mitochondrial dynamics (PubMed:29961568). {ECO:0000250|UniProtKB:Q8R5H6, ECO:0000269|PubMed:29961568, ECO:0000269|PubMed:9889097}. |
| Q92633 | LPAR1 | T335 | 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}. |
| Q92854 | SEMA4D | T813 | 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}. |
| Q969E2 | SCAMP4 | T192 | ochoa | Secretory carrier-associated membrane protein 4 (Secretory carrier membrane protein 4) | Probably involved in membrane protein trafficking. {ECO:0000250}. |
| Q969V6 | MRTFA | T337 | 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}. |
| Q969V6 | MRTFA | T417 | 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}. |
| Q96A47 | ISL2 | T271 | ochoa | Insulin gene enhancer protein ISL-2 (Islet-2) | Transcriptional factor that defines subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways. {ECO:0000250}. |
| Q96B97 | SH3KBP1 | T179 | 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}. |
| Q96DX8 | RTP4 | T183 | ochoa | Receptor-transporting protein 4 (28 kDa interferon-responsive protein) (3CxxC-type zinc finger protein 4) | Chaperone protein that facilitates the trafficking and functional cell surface expression of some G-protein coupled receptors (GPCRs) (PubMed:18836069). Promotes functional expression of the bitter taste receptor TAS2R16 (PubMed:16720576). Also promotes functional expression of the opioid receptor heterodimer OPRD1-OPRM1 (By similarity). In addition, acts as a potent IFN-inducible suppressor of pathogens including lyssavirus rabies, influenza A or yellow fever virus (PubMed:33113352). Mechanistically, associates with the viral replicase, binds viral RNA, and thereby suppresses viral genome amplification that replicates at the endoplasmic reticulum (By similarity). In addition, restores antiviral signaling by interacting with and sequestering influenza A virus protein NS1 (PubMed:39798334). {ECO:0000250|UniProtKB:Q9ER80, ECO:0000269|PubMed:16720576, ECO:0000269|PubMed:18836069, ECO:0000269|PubMed:33113352, ECO:0000269|PubMed:39798334}. |
| Q96GX8 | C16orf74 | T46 | ochoa | Uncharacterized protein C16orf74 | None |
| Q96IF1 | AJUBA | T265 | 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}. |
| Q96JZ2 | HSH2D | T247 | 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}. |
| Q96K80 | ZC3H10 | T173 | 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}. |
| Q96N77 | ZNF641 | T187 | ochoa | Zinc finger protein 641 | Transcriptional activator. Activates transcriptional activities of SRE and AP-1. {ECO:0000269|PubMed:16343441}. |
| Q96PU5 | NEDD4L | T903 | 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}. |
| Q96RU8 | TRIB1 | T257 | ochoa | Tribbles homolog 1 (TRB-1) (G-protein-coupled receptor-induced gene 2 protein) (GIG-2) (SKIP1) | Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase (PubMed:27041596). The COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain (PubMed:26455797). Serves to alter COP1 substrate specificity by directing the activity of COP1 toward CEBPA (PubMed:27041596). Binds selectively the recognition sequence of CEBPA (PubMed:26455797). Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner (By similarity). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (By similarity). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity (PubMed:15299019, PubMed:26455797). {ECO:0000250|UniProtKB:Q8K4K4, ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:26455797, ECO:0000305|PubMed:27041596}. |
| Q99569 | PKP4 | T445 | 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}. |
| Q99698 | LYST | T2122 | 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}. |
| Q99704 | DOK1 | T437 | 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}. |
| Q99788 | CMKLR1 | T342 | ochoa | Chemerin-like receptor 1 (Chemokine-like receptor 1) (G-protein coupled receptor ChemR23) (G-protein coupled receptor DEZ) | Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with RARRES2 initiates activation of G proteins G(i)/G(o) and beta-arrestin pathways inducing cellular responses via second messenger pathways such as intracellular calcium mobilization, phosphorylation of MAP kinases MAPK1/MAPK3 (ERK1/2), TYRO3, MAPK14/P38MAPK and PI3K leading to multifunctional effects, like reduction of immune responses, enhancing of adipogenesis and angionesis (PubMed:27716822). Resolvin E1 down-regulates cytokine production in macrophages by reducing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B. Positively regulates adipogenesis and adipocyte metabolism. {ECO:0000269|PubMed:15728234, ECO:0000269|PubMed:15753205, ECO:0000269|PubMed:20044979, ECO:0000269|PubMed:27716822}.; FUNCTION: (Microbial infection) Acts as a coreceptor for several SIV strains (SIVMAC316, SIVMAC239, SIVMACL7E-FR and SIVSM62A), as well as a primary HIV-1 strain (92UG024-2). {ECO:0000269|PubMed:9603476}. |
| Q99962 | SH3GL2 | T280 | ochoa | Endophilin-A1 (EEN-B1) (Endophilin-1) (SH3 domain protein 2A) (SH3 domain-containing GRB2-like protein 2) | Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes. {ECO:0000250|UniProtKB:Q62420}. |
| Q9BQE3 | TUBA1C | T94 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C 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. |
| Q9BVT8 | TMUB1 | T87 | 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}. |
| Q9BW27 | NUP85 | T90 | ochoa | Nuclear pore complex protein Nup85 (85 kDa nucleoporin) (FROUNT) (Nucleoporin Nup75) (Nucleoporin Nup85) (Pericentrin-1) | Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance (PubMed:12718872). As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP96/Nup98 and NUP153 to the nucleus (PubMed:12718872). The Nup107-160 complex seems to be required for spindle assembly during mitosis (PubMed:16807356). NUP85 is required for membrane clustering of CCL2-activated CCR2 (PubMed:15995708). Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol 3-kinase-Rac-lammellipodium protrusion cascade (PubMed:15995708). Involved in nephrogenesis (PubMed:30179222). {ECO:0000269|PubMed:12718872, ECO:0000269|PubMed:15995708, ECO:0000269|PubMed:16807356, ECO:0000269|PubMed:30179222}. |
| Q9BXS5 | AP1M1 | T144 | ochoa | AP-1 complex subunit mu-1 (AP-mu chain family member mu1A) (Adaptor protein complex AP-1 subunit mu-1) (Adaptor-related protein complex 1 subunit mu-1) (Clathrin assembly protein complex 1 mu-1 medium chain 1) (Clathrin coat assembly protein AP47) (Clathrin coat-associated protein AP47) (Golgi adaptor HA1/AP1 adaptin mu-1 subunit) (Mu-adaptin 1) (Mu1A-adaptin) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. |
| Q9BY89 | KIAA1671 | T1380 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYT3 | STK33 | T382 | psp | Serine/threonine-protein kinase 33 (EC 2.7.11.1) | Serine/threonine protein kinase required for spermatid differentiation and male fertility (PubMed:37146716, PubMed:38781365). Promotes sperm flagella assembly during spermatogenesis by mediating phosphorylation of fibrous sheath proteins AKAP3 and AKAP4 (By similarity). Also phosphorylates vimentin/VIM, thereby regulating the dynamic behavior of the intermediate filament cytoskeleton (By similarity). {ECO:0000250|UniProtKB:Q924X7, ECO:0000269|PubMed:37146716, ECO:0000269|PubMed:38781365}. |
| Q9BZH6 | WDR11 | T219 | ochoa | WD repeat-containing protein 11 (Bromodomain and WD repeat-containing protein 2) (WD repeat-containing protein 15) | Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis (PubMed:29263200). Regulates the proteolytic processing of GLI3 and cooperates with the transcription factor EMX1 in the induction of downstream Hh pathway gene expression and gonadotropin-releasing hormone production (PubMed:29263200). WDR11 complex facilitates the tethering of Adaptor protein-1 complex (AP-1)-derived vesicles. WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). {ECO:0000269|PubMed:29263200, ECO:0000269|PubMed:29426865}. |
| Q9BZL4 | PPP1R12C | T425 | 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}. |
| Q9BZQ8 | NIBAN1 | T590 | ochoa | Protein Niban 1 (Cell growth-inhibiting gene 39 protein) (Protein FAM129A) | Regulates phosphorylation of a number of proteins involved in translation regulation including EIF2A, EIF4EBP1 and RPS6KB1. May be involved in the endoplasmic reticulum stress response (By similarity). {ECO:0000250}. |
| Q9C0B5 | ZDHHC5 | T324 | 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}. |
| Q9C0B5 | ZDHHC5 | T436 | 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}. |
| Q9C0B5 | ZDHHC5 | T521 | 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}. |
| Q9GZR7 | DDX24 | T321 | ochoa | ATP-dependent RNA helicase DDX24 (EC 3.6.4.13) (DEAD box protein 24) | ATP-dependent RNA helicase that plays a role in various aspects of RNA metabolism including pre-mRNA splicing and is thereby involved in different biological processes such as cell cycle regulation or innate immunity (PubMed:24204270, PubMed:24980433). Plays an inhibitory role in TP53 transcriptional activity and subsequently in TP53 controlled cell growth arrest and senescence by inhibiting its EP300 mediated acetylation (PubMed:25867071). Negatively regulates cytosolic RNA-mediated innate immune signaling at least in part by affecting RIPK1/IRF7 interactions. Alternatively, possesses antiviral activity by recognizing gammaherpesvirus transcripts in the context of lytic reactivation (PubMed:36298642). Plays an essential role in cell cycle regulation in vascular smooth muscle cells by interacting with and regulating FANCA (Fanconi anemia complementation group A) mRNA (By similarity). {ECO:0000250|UniProtKB:Q9ESV0, ECO:0000269|PubMed:24204270, ECO:0000269|PubMed:24980433, ECO:0000269|PubMed:25867071, ECO:0000269|PubMed:36298642}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 infection by promoting Rev-dependent nuclear export of viral RNAs and their packaging into virus particles (PubMed:24204270). {ECO:0000269|PubMed:18289627, ECO:0000269|PubMed:24204270}. |
| Q9GZT9 | EGLN1 | T405 | 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}. |
| Q9H165 | BCL11A | T716 | ochoa | BCL11 transcription factor A (B-cell CLL/lymphoma 11A) (B-cell lymphoma/leukemia 11A) (BCL-11A) (COUP-TF-interacting protein 1) (Ecotropic viral integration site 9 protein homolog) (EVI-9) (Zinc finger protein 856) | Transcription factor (PubMed:16704730, PubMed:29606353). Associated with the BAF SWI/SNF chromatin remodeling complex (PubMed:23644491, PubMed:39607926). Binds to the 5'-TGACCA-3' sequence motif in regulatory regions of target genes, including a distal promoter of the HBG1 hemoglobin subunit gamma-1 gene (PubMed:29606353, PubMed:39423807). Involved in regulation of the developmental switch from gamma- to beta-globin, probably via direct repression of HBG1; hence indirectly repressing fetal hemoglobin (HbF) level (PubMed:26375765, PubMed:29606353, PubMed:39423807, PubMed:39607926). Involved in brain development (PubMed:27453576). May play a role in hematopoiesis (By similarity). Essential factor in lymphopoiesis required for B-cell formation in fetal liver (By similarity). May function as a modulator of the transcriptional repression activity of NR2F2 (By similarity). {ECO:0000250|UniProtKB:Q9QYE3, ECO:0000269|PubMed:16704730, ECO:0000269|PubMed:23644491, ECO:0000269|PubMed:29606353, ECO:0000269|PubMed:39423807, ECO:0000269|PubMed:39607926, ECO:0000303|PubMed:26375765, ECO:0000303|PubMed:27453576}. |
| Q9H1A4 | ANAPC1 | T701 | 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}. |
| Q9H257 | CARD9 | T95 | psp | 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}. |
| Q9H2X6 | HIPK2 | T1114 | psp | 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}. |
| Q9H3D4 | TP63 | T281 | psp | Tumor protein 63 (p63) (Chronic ulcerative stomatitis protein) (CUSP) (Keratinocyte transcription factor KET) (Transformation-related protein 63) (TP63) (Tumor protein p73-like) (p73L) (p40) (p51) | Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter. {ECO:0000269|PubMed:11641404, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12446779, ECO:0000269|PubMed:12446784, ECO:0000269|PubMed:20123734, ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:9774969}. |
| Q9H4L5 | OSBPL3 | T195 | 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}. |
| Q9H6F5 | CCDC86 | T206 | ochoa | Coiled-coil domain-containing protein 86 (Cytokine-induced protein with coiled-coil domain) | Required for proper chromosome segregation during mitosis and error-free mitotic progression. {ECO:0000269|PubMed:36695333}. |
| Q9HBE1 | PATZ1 | T262 | 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 | T297 | ochoa | Interleukin-21 receptor (IL-21 receptor) (IL-21R) (Novel interleukin receptor) (CD antigen CD360) | This is a receptor for interleukin-21. |
| Q9NRI5 | DISC1 | T50 | psp | Disrupted in schizophrenia 1 protein | Involved in the regulation of multiple aspects of embryonic and adult neurogenesis (PubMed:19303846, PubMed:19502360). Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus (By similarity). Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance (PubMed:19303846). Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation (By similarity). Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A (By similarity). Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development (PubMed:19502360). Inhibits ATF4 transcription factor activity in neurons by disrupting ATF4 dimerization and DNA-binding (By similarity). Plays a role, together with PCNT, in the microtubule network formation (PubMed:18955030). {ECO:0000250|UniProtKB:Q811T9, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:19303846, ECO:0000269|PubMed:19502360}. |
| Q9NV70 | EXOC1 | T468 | ochoa | Exocyst complex component 1 (Exocyst complex component Sec3) | Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.; FUNCTION: (Microbial infection) Has an antiviral effect against flaviviruses by affecting viral RNA transcription and translation through the sequestration of elongation factor 1-alpha (EEF1A1). This results in decreased viral RNA synthesis and decreased viral protein translation. {ECO:0000269|PubMed:19889084}. |
| Q9NVM1 | EVA1B | T146 | ochoa | Protein eva-1 homolog B (Protein FAM176B) | None |
| Q9NW68 | BSDC1 | T343 | ochoa | BSD domain-containing protein 1 | None |
| Q9NXH8 | TOR4A | T55 | ochoa | Torsin-4A (Torsin family 4 member A) | None |
| Q9NY65 | TUBA8 | T94 | 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. |
| Q9NZB2 | FAM120A | T1068 | 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}. |
| Q9NZM5 | NOP53 | T91 | 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}. |
| Q9P2D1 | CHD7 | T2227 | 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}. |
| Q9UBY5 | LPAR3 | T333 | 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. |
| Q9UDT6 | CLIP2 | T198 | 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}. |
| Q9UER7 | DAXX | T639 | 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}. |
| Q9UKA4 | AKAP11 | T1583 | 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. |
| Q9UKI8 | TLK1 | T75 | 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}. |
| Q9ULM3 | YEATS2 | T534 | ochoa | YEATS domain-containing protein 2 | Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:18838386, PubMed:19103755, PubMed:27103431). YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}. |
| Q9ULM3 | YEATS2 | T604 | ochoa | YEATS domain-containing protein 2 | Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:18838386, PubMed:19103755, PubMed:27103431). YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}. |
| Q9UMN6 | KMT2B | T939 | 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 | T723 | 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}. |
| Q9UNF0 | PACSIN2 | T370 | ochoa | Protein kinase C and casein kinase substrate in neurons protein 2 (Syndapin-2) (Syndapin-II) (SdpII) | Regulates the morphogenesis and endocytosis of caveolae (By similarity). Lipid-binding protein that is able to promote the tubulation of the phosphatidic acid-containing membranes it preferentially binds. Plays a role in intracellular vesicle-mediated transport. Involved in the endocytosis of cell-surface receptors like the EGF receptor, contributing to its internalization in the absence of EGF stimulus (PubMed:21693584, PubMed:23129763, PubMed:23236520, PubMed:23596323). Essential for endothelial organization in sprouting angiogenesis, modulates CDH5-based junctions. Facilitates endothelial front-rear polarity during migration by recruiting EHD4 and MICALL1 to asymmetric adherens junctions between leader and follower cells (By similarity). {ECO:0000250|UniProtKB:Q9WVE8, ECO:0000269|PubMed:21693584, ECO:0000269|PubMed:23129763, ECO:0000269|PubMed:23236520, ECO:0000269|PubMed:23596323}.; FUNCTION: (Microbial infection) Specifically enhances the efficiency of HIV-1 virion spread by cell-to-cell transfer (PubMed:29891700). Also promotes the protrusion engulfment during cell-to-cell spread of bacterial pathogens like Listeria monocytogenes (PubMed:31242077). Involved in lipid droplet formation, which is important for HCV virion assembly (PubMed:31801866). {ECO:0000269|PubMed:29891700, ECO:0000269|PubMed:31242077, ECO:0000269|PubMed:31801866}. |
| Q9UPM8 | AP4E1 | T723 | ochoa | AP-4 complex subunit epsilon-1 (AP-4 adaptor complex subunit epsilon) (Adaptor-related protein complex 4 subunit epsilon-1) (Epsilon subunit of AP-4) (Epsilon-adaptin) | Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}. |
| Q9UPN4 | CEP131 | T248 | 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 | T1449 | 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}. |
| Q9UQE7 | SMC3 | T69 | 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}. |
| Q9Y261 | FOXA2 | T431 | ochoa | Hepatocyte nuclear factor 3-beta (HNF-3-beta) (HNF-3B) (Forkhead box protein A2) (Transcription factor 3B) (TCF-3B) | Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. {ECO:0000250}. |
| Q9Y2J4 | AMOTL2 | T45 | 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}. |
| Q9Y2K1 | ZBTB1 | T299 | ochoa | Zinc finger and BTB domain-containing protein 1 | Acts as a transcriptional repressor (PubMed:20797634). Represses cAMP-responsive element (CRE)-mediated transcriptional activation (PubMed:21706167). In addition, has a role in translesion DNA synthesis. Requires for UV-inducible RAD18 loading, PCNA monoubiquitination, POLH recruitment to replication factories and efficient translesion DNA synthesis (PubMed:24657165). Plays a key role in the transcriptional regulation of T lymphocyte development (By similarity). {ECO:0000250|UniProtKB:Q91VL9, ECO:0000269|PubMed:20797634, ECO:0000269|PubMed:21706167, ECO:0000269|PubMed:24657165}. |
| Q9Y2U5 | MAP3K2 | T516 | ochoa | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| Q9Y2W1 | THRAP3 | T230 | 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}. |
| Q9Y2X9 | ZNF281 | T801 | 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}. |
| Q9Y4H2 | IRS2 | T777 | 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}. |
| Q9Y4L1 | HYOU1 | T962 | 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}. |
| Q9Y512 | SAMM50 | T129 | ochoa | Sorting and assembly machinery component 50 homolog (Transformation-related gene 3 protein) (TRG-3) | Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes (PubMed:22252321, PubMed:25781180). Required for the assembly of TOMM40 into the TOM complex (PubMed:15644312). {ECO:0000269|PubMed:15644312, ECO:0000269|PubMed:22252321, ECO:0000269|PubMed:25781180}. |
| Q9Y6M4 | CSNK1G3 | T29 | 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}. |
| P14314 | PRKCSH | T469 | 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}. |
| P40926 | MDH2 | T227 | Sugiyama | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P60174 | TPI1 | T214 | 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}. |
| P62826 | RAN | T21 | Sugiyama | GTP-binding nuclear protein Ran (EC 3.6.5.-) (Androgen receptor-associated protein 24) (GTPase Ran) (Ras-like protein TC4) (Ras-related nuclear protein) | GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (PubMed:10400640, PubMed:17209048, PubMed:26272610, PubMed:27306458, PubMed:8276887, PubMed:8636225, PubMed:8692944, PubMed:8896452, PubMed:9351834, PubMed:9428644, PubMed:9822603). Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (PubMed:11336674, PubMed:26272610, PubMed:29040603, PubMed:7819259, PubMed:8636225, PubMed:8692944, PubMed:8896452, PubMed:9351834, PubMed:9428644, PubMed:9822603). Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport (PubMed:8896452, PubMed:9351834, PubMed:9428644). Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (PubMed:20485264). RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (PubMed:10408446, PubMed:29040603). Required for normal progress through mitosis (PubMed:12194828, PubMed:29040603, PubMed:8421051). The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). Acts as a negative regulator of the kinase activity of VRK1 and VRK2 (PubMed:18617507). Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases (PubMed:10400640). {ECO:0000269|PubMed:10400640, ECO:0000269|PubMed:10408446, ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17209048, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:20485264, ECO:0000269|PubMed:26272610, ECO:0000269|PubMed:27306458, ECO:0000269|PubMed:29040603, ECO:0000269|PubMed:7819259, ECO:0000269|PubMed:8276887, ECO:0000269|PubMed:8421051, ECO:0000269|PubMed:8636225, ECO:0000269|PubMed:8692944, ECO:0000269|PubMed:8896452, ECO:0000269|PubMed:9351834, ECO:0000269|PubMed:9428644, ECO:0000269|PubMed:9822603, ECO:0000305|PubMed:26272610}. |
| Q14240 | EIF4A2 | T81 | Sugiyama | 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. |
| Q12965 | MYO1E | T939 | Sugiyama | 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}. |
| P23284 | PPIB | T81 | 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}. |
| P49368 | CCT3 | T430 | Sugiyama | T-complex protein 1 subunit gamma (TCP-1-gamma) (EC 3.6.1.-) (CCT-gamma) (Chaperonin containing T-complex polypeptide 1 subunit 3) (hTRiC5) | 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}. |
| P50990 | CCT8 | T286 | Sugiyama | 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}. |
| Q8WVC0 | LEO1 | T477 | Sugiyama | 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}. |
| O15111 | CHUK | T345 | Sugiyama | 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}. |
| Q9Y3F4 | STRAP | T117 | Sugiyama | 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}. |
| P18827 | SDC1 | T240 | Sugiyama | 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}. |
| Q9H6S0 | YTHDC2 | T994 | Sugiyama | 3'-5' RNA helicase YTHDC2 (EC 3.6.4.13) (YTH domain-containing protein 2) (hYTHDC2) | 3'-5' RNA helicase that plays a key role in the male and female germline by promoting transition from mitotic to meiotic divisions in stem cells (PubMed:26318451, PubMed:29033321, PubMed:29970596). Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs that plays a role in the efficiency of RNA processing and stability (PubMed:26318451, PubMed:29033321). Essential for ensuring a successful progression of the meiotic program in the germline by regulating the level of m6A-containing RNAs (By similarity). Acts by binding and promoting degradation of m6A-containing mRNAs: the 3'-5' RNA helicase activity is required for this process and RNA degradation may be mediated by XRN1 exoribonuclease (PubMed:29033321). Required for both spermatogenesis and oogenesis (By similarity). {ECO:0000250|UniProtKB:B2RR83, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:29033321, ECO:0000269|PubMed:29970596}. |
| P01023 | A2M | T1010 | Sugiyama | Alpha-2-macroglobulin (Alpha-2-M) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5) | Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region, a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase. |
| P62191 | PSMC1 | T230 | Sugiyama | 26S proteasome regulatory subunit 4 (P26s4) (26S proteasome AAA-ATPase subunit RPT2) (Proteasome 26S subunit ATPase 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. PSMC1 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}. |
| P41091 | EIF2S3 | T413 | 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 | T413 | 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}. |
| P00519 | ABL1 | T743 | 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}. |
| P34896 | SHMT1 | T178 | Sugiyama | Serine hydroxymethyltransferase, cytosolic (SHMT) (EC 2.1.2.1) (Glycine hydroxymethyltransferase) (Serine methylase) | Interconversion of serine and glycine (PubMed:24698160, PubMed:8505317). {ECO:0000269|PubMed:24698160, ECO:0000269|PubMed:8505317}. |
| P20618 | PSMB1 | T217 | 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}. |
| P32322 | PYCR1 | T137 | Sugiyama | Pyrroline-5-carboxylate reductase 1, mitochondrial (P5C reductase 1) (P5CR 1) (EC 1.5.1.2) | Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H (PubMed:16730026, PubMed:19648921, PubMed:23024808, PubMed:28258219). At physiologic concentrations, has higher specific activity in the presence of NADH (PubMed:16730026, PubMed:23024808). Involved in the cellular response to oxidative stress (PubMed:16730026, PubMed:19648921). {ECO:0000269|PubMed:16730026, ECO:0000269|PubMed:19648921, ECO:0000269|PubMed:23024808, ECO:0000269|PubMed:28258219}. |
| Q13228 | SELENBP1 | T36 | Sugiyama | 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}. |
| P14314 | PRKCSH | T80 | 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}. |
| P27824 | CANX | T66 | Sugiyama | Calnexin (IP90) (Major histocompatibility complex class I antigen-binding protein p88) (p90) | Calcium-binding protein that interacts with newly synthesized monoglucosylated glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse. |
| Q5JSH3 | WDR44 | T746 | 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}. |
| P08253 | MMP2 | T250 | EPSD|PSP | 72 kDa type IV collagenase (EC 3.4.24.24) (72 kDa gelatinase) (Gelatinase A) (Matrix metalloproteinase-2) (MMP-2) (TBE-1) [Cleaved into: PEX] | Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; FUNCTION: PEX, the C-terminal non-catalytic fragment of MMP2, possesses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; FUNCTION: [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways. |
| Q6UVK1 | CSPG4 | T2252 | SIGNOR | 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}. |
| Q9Y624 | F11R | T92 | SIGNOR|iPTMNet|EPSD | Junctional adhesion molecule A (JAM-A) (Junctional adhesion molecule 1) (JAM-1) (Platelet F11 receptor) (Platelet adhesion molecule 1) (PAM-1) (CD antigen CD321) | Seems to play a role in epithelial tight junction formation. Appears early in primordial forms of cell junctions and recruits PARD3 (PubMed:11489913). The association of the PARD6-PARD3 complex may prevent the interaction of PARD3 with JAM1, thereby preventing tight junction assembly (By similarity). Plays a role in regulating monocyte transmigration involved in integrity of epithelial barrier (By similarity). Ligand for integrin alpha-L/beta-2 involved in memory T-cell and neutrophil transmigration (PubMed:11812992). Involved in platelet activation (PubMed:10753840). {ECO:0000250|UniProtKB:O88792, ECO:0000269|PubMed:10753840, ECO:0000269|PubMed:11489913, ECO:0000269|PubMed:11812992}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus sigma-1. {ECO:0000269|PubMed:11239401}.; FUNCTION: (Microbial infection) Acts as a receptor for Human Rotavirus strain Wa. {ECO:0000269|PubMed:25481868}. |
| P21281 | ATP6V1B2 | T115 | Sugiyama | V-type proton ATPase subunit B, brain isoform (V-ATPase subunit B 2) (Endomembrane proton pump 58 kDa subunit) (HO57) (Vacuolar proton pump subunit B 2) | Non-catalytic 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: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 renal intercalated cells, can partially compensate the lack of ATP6V1B1 and mediate secretion of protons (H+) into the urine under base-line conditions but not in conditions of acid load (By similarity). {ECO:0000250|UniProtKB:P62814, ECO:0000269|PubMed:33065002, ECO:0000303|PubMed:32001091}. |
| O75400 | PRPF40A | T923 | Sugiyama | Pre-mRNA-processing factor 40 homolog A (Fas ligand-associated factor 1) (Formin-binding protein 11) (Formin-binding protein 3) (Huntingtin yeast partner A) (Huntingtin-interacting protein 10) (HIP-10) (Huntingtin-interacting protein A) (Renal carcinoma antigen NY-REN-6) | Binds to WASL/N-WASP and suppresses its translocation from the nucleus to the cytoplasm, thereby inhibiting its cytoplasmic function (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. May play a role in cytokinesis. May be involved in pre-mRNA splicing. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| O75369 | FLNB | T997 | 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. |
| P49327 | FASN | T295 | 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}. |
| P62829 | RPL23 | T118 | 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}. |
| P29322 | EPHA8 | T796 | 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}. |
| Q96PE2 | ARHGEF17 | T751 | EPSD|PSP | 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 | T944 | EPSD|PSP | 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}. |
| P42685 | FRK | T322 | 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}. |
| P45985 | MAP2K4 | T66 | Sugiyama | Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}. |
| P60174 | TPI1 | T76 | 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}. |
| Q14204 | DYNC1H1 | T1309 | 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}. |
| P20290 | BTF3 | T135 | Sugiyama | 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}. |
| O15523 | DDX3Y | T154 | Sugiyama | 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}. |
| P41208 | CETN2 | T45 | Sugiyama | Centrin-2 (Caltractin isoform 1) | Plays a fundamental role in microtubule organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CCP110.; FUNCTION: Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer.; FUNCTION: 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. 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. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. 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. 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.; FUNCTION: As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores. {ECO:0000269|PubMed:22307388, ECO:0000305|PubMed:23591820}. |
| P62701 | RPS4X | T166 | Sugiyama | 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}. |
| Q99729 | HNRNPAB | T106 | Sugiyama | 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. |
| P62258 | YWHAE | T114 | Sugiyama | 14-3-3 protein epsilon (14-3-3E) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}. |
| Q14289 | PTK2B | T853 | Sugiyama | 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}. |
| P29401 | TKT | T249 | 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}. |
| Q6XUX3 | DSTYK | T68 | 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}. |
| P30038 | ALDH4A1 | T511 | 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}. |
| P49368 | CCT3 | T484 | Sugiyama | T-complex protein 1 subunit gamma (TCP-1-gamma) (EC 3.6.1.-) (CCT-gamma) (Chaperonin containing T-complex polypeptide 1 subunit 3) (hTRiC5) | 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}. |
| Q8NE63 | HIPK4 | T462 | 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}. |
| O15355 | PPM1G | T234 | Sugiyama | 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 |
| Q96J92 | WNK4 | T314 | 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}. |
| P55072 | VCP | T249 | Sugiyama | 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}. |
| Q9H093 | NUAK2 | T578 | 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 | T42 | 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}. |
| Q9H422 | HIPK3 | T177 | Sugiyama | Homeodomain-interacting protein kinase 3 (EC 2.7.11.1) (Androgen receptor-interacting nuclear protein kinase) (ANPK) (Fas-interacting serine/threonine-protein kinase) (FIST) (Homolog of protein kinase YAK1) | Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}. |
| Q9BYP7 | WNK3 | T287 | 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 | T361 | 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 | T335 | 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}. |
| Q9NWZ3 | IRAK4 | T62 | Sugiyama | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| P17844 | DDX5 | T438 | Sugiyama | 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}. |
| O75369 | FLNB | T1620 | 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. |
| Q9UHD2 | TBK1 | T239 | 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}. |
| P62888 | RPL30 | T69 | Sugiyama | Large ribosomal subunit protein eL30 (60S ribosomal protein L30) | 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}. |
| P62195 | PSMC5 | T194 | Sugiyama | 26S proteasome regulatory subunit 8 (26S proteasome AAA-ATPase subunit RPT6) (Proteasome 26S subunit ATPase 5) (Proteasome subunit p45) (Thyroid hormone receptor-interacting protein 1) (TRIP1) (p45/SUG) | 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. PSMC5 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}. |
| Q9BYP7 | WNK3 | T284 | 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 | T358 | 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 | T332 | 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}. |
| Q13642 | FHL1 | T138 | Sugiyama | Four and a half LIM domains protein 1 (FHL-1) (Skeletal muscle LIM-protein 1) (SLIM) (SLIM-1) | May have an involvement in muscle development or hypertrophy. |
| O75683 | SURF6 | T232 | Sugiyama | Surfeit locus protein 6 | Binds to both DNA and RNA in vitro, with a stronger binding capacity for RNA. May represent a nucleolar constitutive protein involved in ribosomal biosynthesis or assembly (By similarity). {ECO:0000250}. |
| P12268 | IMPDH2 | T147 | Sugiyama | 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}. |
| A0A0B4J1V8 | PPAN-P2RY11 | T233 | ochoa | HCG2039996 (PPAN-P2RY11 readthrough) | None |
| A0A0C4DFX4 | None | T2659 | ochoa | Snf2 related CREBBP activator protein | None |
| O14497 | ARID1A | T1514 | 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}. |
| O15061 | SYNM | T626 | 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}. |
| O15446 | POLR1G | T159 | 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}. |
| O60716 | CTNND1 | T611 | 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}. |
| O95684 | CEP43 | T144 | 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}. |
| P09467 | FBP1 | T28 | ochoa | 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 | T1210 | ochoa | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P0DJD1 | RGPD2 | T1218 | ochoa | RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) | None |
| P10636 | MAPT | T173 | 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}. |
| P10636 | MAPT | T386 | 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}. |
| P11055 | MYH3 | T256 | ochoa | Myosin-3 (Muscle embryonic myosin heavy chain) (Myosin heavy chain 3) (Myosin heavy chain, fast skeletal muscle, embryonic) (SMHCE) | Muscle contraction. |
| P12532 | CKMT1A | T322 | ochoa | Creatine kinase U-type, mitochondrial (EC 2.7.3.2) (Acidic-type mitochondrial creatine kinase) (Mia-CK) (Ubiquitous mitochondrial creatine kinase) (U-MtCK) | 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. |
| P12882 | MYH1 | T258 | ochoa | Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) | Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}. |
| P12883 | MYH7 | T255 | 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}. |
| P13051 | UNG | T31 | ochoa | Uracil-DNA glycosylase (UDG) (EC 3.2.2.27) | Uracil-DNA glycosylase that hydrolyzes the N-glycosidic bond between uracil and deoxyribose in single- and double-stranded DNA (ssDNA and dsDNA) to release a free uracil residue and form an abasic (apurinic/apyrimidinic; AP) site. Excises uracil residues arising as a result of misincorporation of dUMP residues by DNA polymerase during replication or due to spontaneous or enzymatic deamination of cytosine (PubMed:12958596, PubMed:15967827, PubMed:17101234, PubMed:22521144, PubMed:7671300, PubMed:8900285, PubMed:9016624, PubMed:9776759). Mediates error-free base excision repair (BER) of uracil at replication forks. According to the model, it is recruited by PCNA to S-phase replication forks to remove misincorporated uracil at U:A base mispairs in nascent DNA strands. Via trimeric RPA it is recruited to ssDNA stretches ahead of the polymerase to allow detection and excision of deaminated cytosines prior to replication. The resultant AP sites temporarily stall replication, allowing time to repair the lesion (PubMed:22521144). Mediates mutagenic uracil processing involved in antibody affinity maturation. Processes AICDA-induced U:G base mispairs at variable immunoglobulin (Ig) regions leading to the generation of transversion mutations (PubMed:12958596). Operates at switch sites of Ig constant regions where it mediates Ig isotype class switch recombination. Excises AICDA-induced uracil residues forming AP sites that are subsequently nicked by APEX1 endonuclease. The accumulation of staggered nicks in opposite strands results in double strand DNA breaks that are finally resolved via non-homologous end joining repair pathway (By similarity) (PubMed:12958596). {ECO:0000250|UniProtKB:P97931, ECO:0000269|PubMed:12958596, ECO:0000269|PubMed:15967827, ECO:0000269|PubMed:17101234, ECO:0000269|PubMed:22521144, ECO:0000269|PubMed:7671300, ECO:0000269|PubMed:8900285, ECO:0000269|PubMed:9016624, ECO:0000269|PubMed:9776759}. |
| P13533 | MYH6 | T256 | ochoa | Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) | Muscle contraction. |
| P13535 | MYH8 | T258 | ochoa | Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) | Muscle contraction. |
| P13688 | CEACAM1 | T457 | psp | Cell adhesion molecule CEACAM1 (Biliary glycoprotein 1) (BGP-1) (Carcinoembryonic antigen-related cell adhesion molecule 1) (CEA cell adhesion molecule 1) (CD antigen CD66a) | [Isoform 1]: Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and also functions as an activator during angiogenesis (PubMed:18424730, PubMed:23696226, PubMed:25363763). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors. Plays a role in immune response, of T cells, natural killer (NK) and neutrophils (PubMed:18424730, PubMed:23696226). Upon TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by blocking granule exocytosis by mediating homophilic binding to adjacent cells, allowing interaction with and phosphorylation by LCK and interaction with the TCR/CD3 complex which recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70 (PubMed:18424730). Also inhibits T cell proliferation and cytokine production through inhibition of JNK cascade and plays a crucial role in regulating autoimmunity and anti-tumor immunity by inhibiting T cell through its interaction with HAVCR2 (PubMed:25363763). Upon natural killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-homophilic interactions with CEACAM1 on the target cell and lead to cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation (PubMed:23696226). Upon neutrophils activation negatively regulates IL1B production by recruiting PTPN6 to a SYK-TLR4-CEACAM1 complex, that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome. Down-regulates neutrophil production by acting as a coinhibitory receptor for CSF3R by down-regulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (By similarity). Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (By similarity). Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis. This inernalization promotes interaction with FASN leading to receptor-mediated insulin degradation and to reduction of FASN activity leading to negative regulation of fatty acid synthesis. INSR-mediated phosphorylation also provokes a down-regulation of cell proliferation through SHC1 interaction resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and phosphatidylinositol 3-kinase pathways (By similarity). Functions as activator in angiogenesis by promoting blood vessel remodeling through endothelial cell differentiation and migration and in arteriogenesis by increasing the number of collateral arteries and collateral vessel calibers after ischemia. Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (By similarity). Down-regulates cell growth in response to EGF through its interaction with SHC1 that mediates interaction with EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (By similarity). Inhibits cell migration and cell scattering through interaction with FLNA; interferes with the interaction of FLNA with RALA (PubMed:16291724). Mediates bile acid transport activity in a phosphorylation dependent manner (By similarity). Negatively regulates osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:16291724, ECO:0000269|PubMed:18424730, ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25363763}.; FUNCTION: [Isoform 8]: Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Promotes populations of T cells regulating IgA production and secretion associated with control of the commensal microbiota and resistance to enteropathogens (By similarity). {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809}. |
| P20138 | CD33 | T303 | ochoa | Myeloid cell surface antigen CD33 (Sialic acid-binding Ig-like lectin 3) (Siglec-3) (gp67) (CD antigen CD33) | Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state (PubMed:10611343, PubMed:11320212, PubMed:15597323). Preferentially recognizes and binds alpha-2,3- and more avidly alpha-2,6-linked sialic acid-bearing glycans (PubMed:7718872). Upon engagement of ligands such as C1q or syalylated glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in CD33 cytoplasmic tail are phosphorylated by Src-like kinases such as LCK (PubMed:10887109, PubMed:28325905). These phosphorylations provide docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:10206955, PubMed:10556798, PubMed:10887109). In turn, these phosphatases regulate downstream pathways through dephosphorylation of signaling molecules (PubMed:10206955, PubMed:10887109). One of the repressive effect of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K (PubMed:15597323). {ECO:0000269|PubMed:10206955, ECO:0000269|PubMed:10556798, ECO:0000269|PubMed:10611343, ECO:0000269|PubMed:10887109, ECO:0000269|PubMed:11320212, ECO:0000269|PubMed:15597323, ECO:0000269|PubMed:28325905, ECO:0000269|PubMed:7718872}. |
| P21728 | DRD1 | T245 | psp | D(1A) dopamine receptor (Dopamine D1 receptor) | Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase. |
| P25705 | ATP5F1A | T46 | 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}. |
| P26368 | U2AF2 | T296 | ochoa | Splicing factor U2AF 65 kDa subunit (U2 auxiliary factor 65 kDa subunit) (hU2AF(65)) (hU2AF65) (U2 snRNP auxiliary factor large subunit) | Plays a role in pre-mRNA splicing and 3'-end processing (PubMed:17024186). By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing (PubMed:21536736). Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals (PubMed:17024186). {ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:19470458, ECO:0000269|PubMed:19574390, ECO:0000269|PubMed:21536736}. |
| P28827 | PTPRM | T873 | ochoa | Receptor-type tyrosine-protein phosphatase mu (Protein-tyrosine phosphatase mu) (R-PTP-mu) (EC 3.1.3.48) | Receptor protein-tyrosine phosphatase that mediates homotypic cell-cell interactions and plays a role in adipogenic differentiation via modulation of p120 catenin/CTNND1 phosphorylation (PubMed:10753936, PubMed:17761881). Promotes CTNND1 dephosphorylation and prevents its cytoplasmic localization where it inhibits SLC2A4 membrane trafficking. In turn, SLC2A4 is directed to the plasma membrane and performs its glucose transporter function (PubMed:21998202). {ECO:0000269|PubMed:10753936, ECO:0000269|PubMed:16456543, ECO:0000269|PubMed:17761881, ECO:0000269|PubMed:21998202}. |
| P29374 | ARID4A | T1105 | ochoa | AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) | DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}. |
| P35228 | NOS2 | T63 | ochoa | Nitric oxide synthase, inducible (EC 1.14.13.39) (Hepatocyte NOS) (HEP-NOS) (Inducible NO synthase) (Inducible NOS) (iNOS) (NOS type II) (Peptidyl-cysteine S-nitrosylase NOS2) | Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8 (PubMed:19688109). {ECO:0000250|UniProtKB:P29477, ECO:0000269|PubMed:19688109, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:7504305, ECO:0000269|PubMed:7531687, ECO:0000269|PubMed:7544004, ECO:0000269|PubMed:7682706}. |
| P35611 | ADD1 | T417 | ochoa | Alpha-adducin (Erythrocyte adducin subunit alpha) | Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin. |
| P42684 | ABL2 | T68 | ochoa | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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. 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). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P43686 | PSMC4 | T25 | ochoa|psp | 26S proteasome regulatory subunit 6B (26S proteasome AAA-ATPase subunit RPT3) (MB67-interacting protein) (MIP224) (Proteasome 26S subunit ATPase 4) (Tat-binding protein 7) (TBP-7) | 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. PSMC4 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, ECO:0000269|PubMed:8060531}. |
| P46379 | BAG6 | T102 | ochoa | Large proline-rich protein BAG6 (BAG family molecular chaperone regulator 6) (BCL2-associated athanogene 6) (BAG-6) (HLA-B-associated transcript 3) (Protein G3) (Protein Scythe) | ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client 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:20516149, PubMed:21636303, PubMed:21743475, PubMed:28104892). 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:20516149, PubMed:20676083, PubMed:25535373, PubMed:28104892). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome (PubMed:24981174, PubMed:27193484, PubMed:28104892). SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins (PubMed:23129660, PubMed:25179605, PubMed:27193484). 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). BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (By similarity). BAG6 is also 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. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress (PubMed:26565908). By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis (By similarity). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (By similarity). 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:Q9Z1R2, ECO:0000269|PubMed:20516149, ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; FUNCTION: Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity (PubMed:17403783). When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2) (PubMed:18765639). {ECO:0000269|PubMed:17403783, ECO:0000269|PubMed:18765639}.; FUNCTION: Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC). {ECO:0000269|PubMed:18055229, ECO:0000269|PubMed:18852879}.; FUNCTION: Mediates ricin-induced apoptosis. {ECO:0000269|PubMed:14960581}. |
| P48730 | CSNK1D | T387 | ochoa | Casein kinase I isoform delta (CKI-delta) (CKId) (EC 2.7.11.1) (Tau-protein kinase CSNK1D) (EC 2.7.11.26) | Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (By similarity). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. {ECO:0000250|UniProtKB:Q9DC28, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:16027726, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:19043076, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:20407760, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:20696890, ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:21084295, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092}. |
| P49023 | PXN | T318 | 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}. |
| P49792 | RANBP2 | T1839 | 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 | T2201 | 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}. |
| P54296 | MYOM2 | T676 | 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. |
| P55317 | FOXA1 | T317 | ochoa | Hepatocyte nuclear factor 3-alpha (HNF-3-alpha) (HNF-3A) (Forkhead box protein A1) (Transcription factor 3A) (TCF-3A) | Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in estrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles (By similarity). Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription; required for ESR1 binding to the NKX2-1 promoter in breast cancer cells; binds to the RPRM promoter and is required for the estrogen-induced repression of RPRM. Involved in regulation of apoptosis by inhibiting the expression of BCL2. Involved in cell cycle regulation by activating expression of CDKN1B, alone or in conjunction with BRCA1. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis. {ECO:0000250, ECO:0000269|PubMed:16087863, ECO:0000269|PubMed:16331276, ECO:0000269|PubMed:18358809, ECO:0000269|PubMed:19127412, ECO:0000269|PubMed:19917725}. |
| P60660 | MYL6 | T22 | ochoa | Myosin light polypeptide 6 (17 kDa myosin light chain) (LC17) (Myosin light chain 3) (MLC-3) (Myosin light chain alkali 3) (Myosin light chain A3) (Smooth muscle and nonmuscle myosin light chain alkali 6) | Regulatory light chain of myosin. Does not bind calcium. |
| P62736 | ACTA2 | T151 | ochoa | Actin, aortic smooth muscle (EC 3.6.4.-) (Alpha-actin-2) (Cell growth-inhibiting gene 46 protein) [Cleaved into: Actin, aortic smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P62937 | PPIA | T93 | 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}. |
| P63218 | GNG5 | T50 | ochoa | Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 | Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. |
| P63267 | ACTG2 | T150 | ochoa | Actin, gamma-enteric smooth muscle (EC 3.6.4.-) (Alpha-actin-3) (Gamma-2-actin) (Smooth muscle gamma-actin) [Cleaved into: Actin, gamma-enteric smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68032 | ACTC1 | T151 | ochoa | Actin, alpha cardiac muscle 1 (EC 3.6.4.-) (Alpha-cardiac actin) [Cleaved into: Actin, alpha cardiac muscle 1, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68133 | ACTA1 | T151 | ochoa | Actin, alpha skeletal muscle (EC 3.6.4.-) (Alpha-actin-1) [Cleaved into: Actin, alpha skeletal muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| Q00872 | MYBPC1 | T798 | ochoa | Myosin-binding protein C, slow-type (Slow MyBP-C) (C-protein, skeletal muscle slow isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. Slow skeletal protein that binds to both myosin and actin (PubMed:31025394, PubMed:31264822). In vitro, binds to native thin filaments and modifies the activity of actin-activated myosin ATPase. May modulate muscle contraction or may play a more structural role. {ECO:0000269|PubMed:31025394, ECO:0000269|PubMed:31264822}. |
| Q04637 | EIF4G1 | T211 | 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}. |
| Q12888 | TP53BP1 | T919 | 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 | T211 | 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}. |
| Q16625 | OCLN | T438 | 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}. |
| Q5S007 | LRRK2 | T1343 | 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}. |
| Q5THJ4 | VPS13D | T1032 | 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}. |
| Q5VZ89 | DENND4C | T1599 | 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}. |
| Q5W0Q7 | USPL1 | T196 | ochoa | SUMO-specific isopeptidase USPL1 (EC 3.4.22.-) (Ubiquitin-specific peptidase-like protein 1) (USP-like 1) | SUMO-specific isopeptidase involved in protein desumoylation. Specifically binds SUMO proteins with a higher affinity for SUMO2 and SUMO3 which it cleaves more efficiently. Also able to process full-length SUMO proteins to their mature forms (PubMed:22878415). Plays a key role in RNA polymerase-II-mediated snRNA transcription in the Cajal bodies (PubMed:24413172). Is a component of complexes that can bind to U snRNA genes (PubMed:24413172). {ECO:0000269|PubMed:22878415, ECO:0000269|PubMed:24413172}. |
| Q6ZRS2 | SRCAP | T2836 | 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}. |
| Q7Z3J3 | RGPD4 | T1226 | ochoa | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q7Z434 | MAVS | T398 | 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 | T701 | 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}. |
| Q8N2K0 | ABHD12 | T43 | ochoa | Lysophosphatidylserine lipase ABHD12 (EC 3.1.-.-) (2-arachidonoylglycerol hydrolase ABHD12) (Abhydrolase domain-containing protein 12) (hABHD12) (Monoacylglycerol lipase ABHD12) (EC 3.1.1.23) (Oxidized phosphatidylserine lipase ABHD12) (EC 3.1.-.-) | Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:25290914, PubMed:30237167, PubMed:30420694, PubMed:30643283, PubMed:30720278). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:22969151, PubMed:24027063). Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167). {ECO:0000250|UniProtKB:Q99LR1, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24027063, ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167, ECO:0000269|PubMed:30420694, ECO:0000269|PubMed:30643283, ECO:0000269|PubMed:30720278}. |
| Q8NEL9 | DDHD1 | T136 | ochoa | Phospholipase DDHD1 (EC 3.1.1.111) (EC 3.1.1.32) (DDHD domain-containing protein 1) (Phosphatidic acid-preferring phospholipase A1 homolog) (PA-PLA1) (EC 3.1.1.118) (Phospholipid sn-1 acylhydrolase) | Phospholipase A1 (PLA1) that hydrolyzes ester bonds at the sn-1 position of glycerophospholipids producing a free fatty acid and a lysophospholipid (Probable) (PubMed:20359546, PubMed:22922100). Prefers phosphatidate (1,2-diacyl-sn-glycero-3-phosphate, PA) as substrate in vitro, but can efficiently hydrolyze phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI), as well as a range of other glycerophospholipid substrates such as phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE), phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) and phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol), PG) (Probable) (PubMed:20359546). Involved in the regulation of the endogenous content of polyunsaturated PI and PS lipids in the nervous system. Changes in these lipids extend to downstream metabolic products like PI phosphates PIP and PIP2, which play fundamental roles in cell biology (By similarity). Regulates mitochondrial morphology (PubMed:24599962). These dynamic changes may be due to PA hydrolysis at the mitochondrial surface (PubMed:24599962). May play a regulatory role in spermatogenesis or sperm function (PubMed:24599962). {ECO:0000250|UniProtKB:Q80YA3, ECO:0000269|PubMed:20359546, ECO:0000269|PubMed:22922100, ECO:0000269|PubMed:24599962, ECO:0000303|PubMed:24599962, ECO:0000305|PubMed:37189713}. |
| Q8NHV4 | NEDD1 | T401 | 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}. |
| Q8TAA9 | VANGL1 | T80 | ochoa | Vang-like protein 1 (Loop-tail protein 2 homolog) (LPP2) (Strabismus 2) (Van Gogh-like protein 1) | None |
| Q8WU90 | ZC3H15 | T345 | ochoa | Zinc finger CCCH domain-containing protein 15 (DRG family-regulatory protein 1) (Likely ortholog of mouse immediate early response erythropoietin 4) | Protects DRG1 from proteolytic degradation (PubMed:19819225). Stimulates DRG1 GTPase activity likely by increasing the affinity for the potassium ions (PubMed:23711155). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155}. |
| Q8WUJ0 | STYX | T199 | 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}. |
| Q8WYB5 | KAT6B | T367 | ochoa | Histone acetyltransferase KAT6B (EC 2.3.1.48) (Histone acetyltransferase MOZ2) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4) (MYST-4) (Monocytic leukemia zinc finger protein-related factor) | Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. {ECO:0000269|PubMed:10497217, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:16387653}. |
| Q92547 | TOPBP1 | T1501 | 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}. |
| Q96DE5 | ANAPC16 | T19 | ochoa | Anaphase-promoting complex subunit 16 (APC16) (Cyclosome subunit 16) | 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:20360068). 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:20360068). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:20360068, ECO:0000269|PubMed:29033132}. |
| Q96HC4 | PDLIM5 | T290 | 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}. |
| Q96N67 | DOCK7 | T136 | 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}. |
| Q96PE1 | ADGRA2 | T995 | 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}. |
| Q96RY5 | CRAMP1 | T613 | ochoa | Protein cramped-like (Cramped chromatin regulator homolog 1) (Hematological and neurological expressed 1-like protein) | None |
| Q99436 | PSMB7 | T42 | ochoa | Proteasome subunit beta type-7 (EC 3.4.25.1) (Macropain chain Z) (Multicatalytic endopeptidase complex chain Z) (Proteasome subunit Z) (Proteasome subunit beta-2) (beta-2) | 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, PSMB7 displays a trypsin-like activity. {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| Q99666 | RGPD5 | T1225 | 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 |
| Q9BWH6 | RPAP1 | T272 | 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}. |
| Q9BX40 | LSM14B | T163 | 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}. |
| Q9BZZ5 | API5 | T399 | ochoa | Apoptosis inhibitor 5 (API-5) (Antiapoptosis clone 11 protein) (AAC-11) (Cell migration-inducing gene 8 protein) (Fibroblast growth factor 2-interacting factor) (FIF) (Protein XAGL) | Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs. {ECO:0000269|PubMed:10780674, ECO:0000269|PubMed:17112319, ECO:0000269|PubMed:19387494}. |
| Q9H0F6 | SHARPIN | T309 | ochoa | Sharpin (Shank-associated RH domain-interacting protein) (Shank-interacting protein-like 1) (hSIPL1) | Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:21455173, PubMed:21455180, PubMed:21455181). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). {ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:28481331}. |
| Q9HAU4 | SMURF2 | T144 | 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}. |
| Q9HC78 | ZBTB20 | T428 | ochoa | Zinc finger and BTB domain-containing protein 20 (Dendritic-derived BTB/POZ zinc finger protein) (Zinc finger protein 288) | May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses (PubMed:11352661). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (By similarity). {ECO:0000250|UniProtKB:Q8K0L9, ECO:0000269|PubMed:11352661}. |
| Q9NQ55 | PPAN | T233 | ochoa | Suppressor of SWI4 1 homolog (Ssf-1) (Brix domain-containing protein 3) (Peter Pan homolog) | May have a role in cell growth. |
| Q9NQG6 | MIEF1 | T89 | ochoa | Mitochondrial dynamics protein MIEF1 (Mitochondrial dynamics protein of 51 kDa) (Mitochondrial elongation factor 1) (Smith-Magenis syndrome chromosomal region candidate gene 7 protein-like) (SMCR7-like protein) | Mitochondrial outer membrane protein which regulates mitochondrial fission/fusion dynamics (PubMed:21701560, PubMed:23921378, PubMed:33632269). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. Regulates DNM1L GTPase activity and DNM1L oligomerization. Binds ADP and can also bind GDP, although with lower affinity. Does not bind CDP, UDP, ATP, AMP or GTP. Inhibits DNM1L GTPase activity in the absence of bound ADP. Requires ADP to stimulate DNM1L GTPase activity and the assembly of DNM1L into long, oligomeric tubules with a spiral pattern, as opposed to the ring-like DNM1L oligomers observed in the absence of bound ADP. Does not require ADP for its function in recruiting DNM1L. {ECO:0000269|PubMed:21508961, ECO:0000269|PubMed:21701560, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:24515348, ECO:0000269|PubMed:29083303, ECO:0000269|PubMed:33632269}. |
| Q9NRL3 | STRN4 | T371 | ochoa | Striatin-4 (Zinedin) | Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753, PubMed:32640226). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling (PubMed:32640226). Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (Probable). Key regulator of the expanded Hippo signaling pathway by interacting and allowing the inhibition of MAP4K kinases by the STRIPAK complex (PubMed:32640226). {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:32640226, ECO:0000305|PubMed:26876214}. |
| Q9NYW0 | TAS2R10 | T212 | ochoa | Taste receptor type 2 member 10 (T2R10) (Taste receptor family B member 2) (TRB2) | Gustducin-coupled strychnine receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. {ECO:0000269|PubMed:15759003}. |
| Q9P2A4 | ABI3 | T163 | ochoa | ABI gene family member 3 (New molecule including SH3) (Nesh) | May inhibit tumor metastasis (By similarity). In vitro, reduces cell motility. {ECO:0000250, ECO:0000269|PubMed:11956071}. |
| Q9P2F8 | SIPA1L2 | T184 | ochoa | Signal-induced proliferation-associated 1-like protein 2 (SIPA1-like protein 2) | None |
| Q9UKX2 | MYH2 | T258 | ochoa | Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}. |
| Q9UKX2 | MYH2 | T594 | ochoa | Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}. |
| Q9UKX3 | MYH13 | T257 | ochoa | Myosin-13 (Myosin heavy chain 13) (Myosin heavy chain, skeletal muscle, extraocular) (MyHC-EO) (Myosin heavy chain, skeletal muscle, laryngeal) (MyHC-IIL) (Superfast myosin) | Fast twitching myosin mediating the high-velocity and low-tension contractions of specific striated muscles. {ECO:0000269|PubMed:23908353}. |
| Q9ULK5 | VANGL2 | T76 | ochoa | Vang-like protein 2 (Loop-tail protein 1 homolog) (Strabismus 1) (Van Gogh-like protein 2) | Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate. Plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea. Required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process. Required for cell surface localization of FZD3 and FZD6 in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q91ZD4}. |
| Q9UN19 | DAPP1 | T119 | 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}. |
| Q9UPM8 | AP4E1 | T672 | ochoa | AP-4 complex subunit epsilon-1 (AP-4 adaptor complex subunit epsilon) (Adaptor-related protein complex 4 subunit epsilon-1) (Epsilon subunit of AP-4) (Epsilon-adaptin) | Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}. |
| Q9UPS6 | SETD1B | T360 | ochoa | Histone-lysine N-methyltransferase SETD1B (EC 2.1.1.364) (Lysine N-methyltransferase 2G) (SET domain-containing protein 1B) (hSET1B) | 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:17355966, 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:17355966, PubMed:25561738). Plays an essential role in regulating the transcriptional programming of multipotent hematopoietic progenitor cells and lymphoid lineage specification during hematopoiesis (By similarity). {ECO:0000250|UniProtKB:Q8CFT2, ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:25561738}. |
| Q9UPT8 | ZC3H4 | T1265 | 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}. |
| Q9Y2I1 | NISCH | T1019 | 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}. |
| Q9Y4B5 | MTCL1 | T1804 | 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}. |
| Q9Y623 | MYH4 | T258 | ochoa | Myosin-4 (Myosin heavy chain 2b) (MyHC-2b) (Myosin heavy chain 4) (Myosin heavy chain IIb) (MyHC-IIb) (Myosin heavy chain, skeletal muscle, fetal) | Muscle contraction. |
| Q9Y6Q9 | NCOA3 | T1067 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| P05187 | ALPP | T185 | 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}. |
| P09923 | ALPI | T182 | Sugiyama | Intestinal-type alkaline phosphatase (IAP) (Intestinal alkaline phosphatase) (EC 3.1.3.1) | Alkaline phosphatase that can hydrolyze various phosphate compounds. {ECO:0000250|UniProtKB:P15693}. |
| P60842 | EIF4A1 | T80 | Sugiyama | 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}. |
| Q9P2J5 | LARS1 | T386 | Sugiyama | Leucine--tRNA ligase, cytoplasmic (EC 6.1.1.4) (Leucyl-tRNA synthetase) (LeuRS) (cLRS) | Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: Leu is initially activated by ATP to form a leucyl-adenylate (Leu-AMP) intermediate; then the leucyl moiety is transferred to the acceptor 3' end of the tRNA to yield leucyl-tRNA (PubMed:25051973). To improve the fidelity of catalytic reactions, it is also able to hydrolyze misactivated aminoacyl-adenylate intermediates (pre-transfer editing) and mischarged aminoacyl-tRNAs (post-transfer editing) (PubMed:25051973). {ECO:0000269|PubMed:19426743, ECO:0000269|PubMed:25051973, ECO:0000269|PubMed:32232361}. |
| P67809 | YBX1 | T126 | Sugiyama | 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}. |
| P60174 | TPI1 | T173 | 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}. |
| P49588 | AARS1 | T240 | 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}. |
| P29320 | EPHA3 | T933 | Sugiyama | Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}. |
| O60841 | EIF5B | T289 | Sugiyama | Eukaryotic translation initiation factor 5B (eIF-5B) (EC 3.6.5.3) (Translation initiation factor IF-2) | Plays a role in translation initiation (PubMed:10659855, PubMed:35732735). Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon (PubMed:10659855, PubMed:35732735). Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex (PubMed:12569173, PubMed:35732735). Is released after formation of the 80S initiation complex (PubMed:35732735). Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes (PubMed:10659855, PubMed:35732735). In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit (PubMed:10659855). {ECO:0000269|PubMed:10659855, ECO:0000269|PubMed:12569173, ECO:0000269|PubMed:35732735}. |
| P11047 | LAMC1 | T1127 | 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. |
| Q14498 | RBM39 | T347 | Sugiyama | RNA-binding protein 39 (CAPER alpha) (CAPERalpha) (Hepatocellular carcinoma protein 1) (RNA-binding motif protein 39) (RNA-binding region-containing protein 2) (Splicing factor HCC1) | RNA-binding protein that acts as a pre-mRNA splicing factor (PubMed:15694343, PubMed:24795046, PubMed:28302793, PubMed:28437394, PubMed:31271494). Acts by promoting exon inclusion via regulation of exon cassette splicing (PubMed:31271494). Also acts as a transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1, independently of the pre-mRNA splicing factor activity (By similarity). {ECO:0000250|UniProtKB:Q8VH51, ECO:0000269|PubMed:15694343, ECO:0000269|PubMed:24795046, ECO:0000269|PubMed:28302793, ECO:0000269|PubMed:28437394, ECO:0000269|PubMed:31271494}. |
| Q10713 | PMPCA | T294 | Sugiyama | Mitochondrial-processing peptidase subunit alpha (Alpha-MPP) (Inactive zinc metalloprotease alpha) (P-55) | Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins. {ECO:0000269|PubMed:25808372}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-2262752 | Cellular responses to stress | 1.110223e-16 | 15.955 |
| R-HSA-8953897 | Cellular responses to stimuli | 1.110223e-16 | 15.955 |
| R-HSA-422475 | Axon guidance | 1.332268e-14 | 13.875 |
| R-HSA-68886 | M Phase | 2.897682e-14 | 13.538 |
| R-HSA-9675108 | Nervous system development | 7.183143e-14 | 13.144 |
| R-HSA-438064 | Post NMDA receptor activation events | 1.237122e-12 | 11.908 |
| R-HSA-1640170 | Cell Cycle | 2.240763e-12 | 11.650 |
| R-HSA-69278 | Cell Cycle, Mitotic | 7.051804e-12 | 11.152 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 1.540368e-11 | 10.812 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 3.109613e-11 | 10.507 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 1.435452e-10 | 9.843 |
| R-HSA-68882 | Mitotic Anaphase | 1.788143e-10 | 9.748 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 2.084156e-10 | 9.681 |
| R-HSA-69275 | G2/M Transition | 2.154135e-10 | 9.667 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 2.869932e-10 | 9.542 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 2.994054e-10 | 9.524 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 4.526158e-10 | 9.344 |
| R-HSA-68877 | Mitotic Prometaphase | 6.677230e-10 | 9.175 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 7.079616e-10 | 9.150 |
| R-HSA-2467813 | Separation of Sister Chromatids | 9.025386e-10 | 9.045 |
| R-HSA-437239 | Recycling pathway of L1 | 9.961052e-10 | 9.002 |
| R-HSA-376176 | Signaling by ROBO receptors | 1.142854e-09 | 8.942 |
| R-HSA-9833482 | PKR-mediated signaling | 2.623513e-09 | 8.581 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 4.055192e-09 | 8.392 |
| R-HSA-9663891 | Selective autophagy | 6.261509e-09 | 8.203 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 6.656406e-09 | 8.177 |
| R-HSA-9646399 | Aggrephagy | 7.239296e-09 | 8.140 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 1.484457e-08 | 7.828 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 1.484457e-08 | 7.828 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 1.922809e-08 | 7.716 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 2.158990e-08 | 7.666 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 3.379447e-08 | 7.471 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 3.443965e-08 | 7.463 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 3.948074e-08 | 7.404 |
| R-HSA-373760 | L1CAM interactions | 4.574357e-08 | 7.340 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 5.895366e-08 | 7.229 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 7.465454e-08 | 7.127 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 1.735596e-07 | 6.761 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 2.488064e-07 | 6.604 |
| R-HSA-109581 | Apoptosis | 2.801838e-07 | 6.553 |
| R-HSA-9948299 | Ribosome-associated quality control | 3.531140e-07 | 6.452 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 3.790660e-07 | 6.421 |
| R-HSA-913531 | Interferon Signaling | 4.222985e-07 | 6.374 |
| R-HSA-156902 | Peptide chain elongation | 8.136904e-07 | 6.090 |
| R-HSA-9612973 | Autophagy | 7.951998e-07 | 6.100 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 8.554455e-07 | 6.068 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 8.968099e-07 | 6.047 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 9.812527e-07 | 6.008 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 9.878758e-07 | 6.005 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 1.135161e-06 | 5.945 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 1.278875e-06 | 5.893 |
| R-HSA-75153 | Apoptotic execution phase | 1.290862e-06 | 5.889 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 1.343874e-06 | 5.872 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 1.434705e-06 | 5.843 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 1.538713e-06 | 5.813 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 1.538713e-06 | 5.813 |
| R-HSA-162582 | Signal Transduction | 1.539043e-06 | 5.813 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 1.712609e-06 | 5.766 |
| R-HSA-380287 | Centrosome maturation | 1.714874e-06 | 5.766 |
| R-HSA-5357801 | Programmed Cell Death | 2.365363e-06 | 5.626 |
| R-HSA-3371556 | Cellular response to heat stress | 2.442916e-06 | 5.612 |
| R-HSA-190828 | Gap junction trafficking | 3.030452e-06 | 5.518 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 3.297331e-06 | 5.482 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 3.297331e-06 | 5.482 |
| R-HSA-1632852 | Macroautophagy | 3.665538e-06 | 5.436 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 3.738796e-06 | 5.427 |
| R-HSA-72764 | Eukaryotic Translation Termination | 4.093302e-06 | 5.388 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 4.093302e-06 | 5.388 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 4.093302e-06 | 5.388 |
| R-HSA-446728 | Cell junction organization | 4.279036e-06 | 5.369 |
| R-HSA-9764561 | Regulation of CDH1 Function | 4.985520e-06 | 5.302 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 5.088674e-06 | 5.293 |
| R-HSA-69620 | Cell Cycle Checkpoints | 5.638758e-06 | 5.249 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 6.209878e-06 | 5.207 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 6.325692e-06 | 5.199 |
| R-HSA-447115 | Interleukin-12 family signaling | 6.325692e-06 | 5.199 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 6.246187e-06 | 5.204 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 8.228913e-06 | 5.085 |
| R-HSA-1500931 | Cell-Cell communication | 7.921651e-06 | 5.101 |
| R-HSA-72649 | Translation initiation complex formation | 8.981792e-06 | 5.047 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 9.053936e-06 | 5.043 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 9.053936e-06 | 5.043 |
| R-HSA-157858 | Gap junction trafficking and regulation | 1.032284e-05 | 4.986 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 1.117525e-05 | 4.952 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 1.242561e-05 | 4.906 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 1.360162e-05 | 4.866 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 1.383835e-05 | 4.859 |
| R-HSA-449147 | Signaling by Interleukins | 1.670461e-05 | 4.777 |
| R-HSA-391251 | Protein folding | 1.715391e-05 | 4.766 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 1.917219e-05 | 4.717 |
| R-HSA-9020591 | Interleukin-12 signaling | 2.031823e-05 | 4.692 |
| R-HSA-2132295 | MHC class II antigen presentation | 2.162331e-05 | 4.665 |
| R-HSA-1266738 | Developmental Biology | 2.198210e-05 | 4.658 |
| R-HSA-70171 | Glycolysis | 2.500114e-05 | 4.602 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 2.733454e-05 | 4.563 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 2.804716e-05 | 4.552 |
| R-HSA-4086400 | PCP/CE pathway | 2.871568e-05 | 4.542 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 3.020742e-05 | 4.520 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 3.088814e-05 | 4.510 |
| R-HSA-9711097 | Cellular response to starvation | 3.337926e-05 | 4.477 |
| R-HSA-168255 | Influenza Infection | 3.325633e-05 | 4.478 |
| R-HSA-2559583 | Cellular Senescence | 3.691309e-05 | 4.433 |
| R-HSA-9824446 | Viral Infection Pathways | 3.709186e-05 | 4.431 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 3.902269e-05 | 4.409 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 4.106027e-05 | 4.387 |
| R-HSA-190861 | Gap junction assembly | 4.220803e-05 | 4.375 |
| R-HSA-5617833 | Cilium Assembly | 4.766022e-05 | 4.322 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 5.371064e-05 | 4.270 |
| R-HSA-3371571 | HSF1-dependent transactivation | 5.499177e-05 | 4.260 |
| R-HSA-8953854 | Metabolism of RNA | 5.762509e-05 | 4.239 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 6.701948e-05 | 4.174 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 7.441088e-05 | 4.128 |
| R-HSA-2408557 | Selenocysteine synthesis | 7.507552e-05 | 4.125 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 8.028885e-05 | 4.095 |
| R-HSA-418990 | Adherens junctions interactions | 8.417282e-05 | 4.075 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 9.023041e-05 | 4.045 |
| R-HSA-192823 | Viral mRNA Translation | 9.838034e-05 | 4.007 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 1.125497e-04 | 3.949 |
| R-HSA-70326 | Glucose metabolism | 1.435012e-04 | 3.843 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 1.451652e-04 | 3.838 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 1.487275e-04 | 3.828 |
| R-HSA-5689603 | UCH proteinases | 1.657282e-04 | 3.781 |
| R-HSA-3371568 | Attenuation phase | 1.726451e-04 | 3.763 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 1.680262e-04 | 3.775 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 1.634289e-04 | 3.787 |
| R-HSA-5610787 | Hedgehog 'off' state | 1.646910e-04 | 3.783 |
| R-HSA-194138 | Signaling by VEGF | 1.773318e-04 | 3.751 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 1.775925e-04 | 3.751 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 1.775925e-04 | 3.751 |
| R-HSA-421270 | Cell-cell junction organization | 1.834169e-04 | 3.737 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 2.274075e-04 | 3.643 |
| R-HSA-1059683 | Interleukin-6 signaling | 2.288753e-04 | 3.640 |
| R-HSA-72766 | Translation | 2.375932e-04 | 3.624 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 2.330939e-04 | 3.632 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 2.274075e-04 | 3.643 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 2.512818e-04 | 3.600 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 2.522444e-04 | 3.598 |
| R-HSA-5683057 | MAPK family signaling cascades | 2.703996e-04 | 3.568 |
| R-HSA-983189 | Kinesins | 2.867267e-04 | 3.543 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 2.925910e-04 | 3.534 |
| R-HSA-2682334 | EPH-Ephrin signaling | 3.112742e-04 | 3.507 |
| R-HSA-4641258 | Degradation of DVL | 3.129313e-04 | 3.505 |
| R-HSA-1592230 | Mitochondrial biogenesis | 3.313473e-04 | 3.480 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 3.585750e-04 | 3.445 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 3.830189e-04 | 3.417 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 4.272994e-04 | 3.369 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 4.272994e-04 | 3.369 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 5.069429e-04 | 3.295 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 5.082512e-04 | 3.294 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 5.173457e-04 | 3.286 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 5.349757e-04 | 3.272 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 5.475495e-04 | 3.262 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 5.620264e-04 | 3.250 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 6.344773e-04 | 3.198 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 6.441038e-04 | 3.191 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 6.716896e-04 | 3.173 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 6.716896e-04 | 3.173 |
| R-HSA-162909 | Host Interactions of HIV factors | 7.030849e-04 | 3.153 |
| R-HSA-8939211 | ESR-mediated signaling | 7.433928e-04 | 3.129 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 7.476989e-04 | 3.126 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 7.476989e-04 | 3.126 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 7.989465e-04 | 3.097 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 7.989465e-04 | 3.097 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 8.365538e-04 | 3.078 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 8.368292e-04 | 3.077 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 8.368292e-04 | 3.077 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 8.368292e-04 | 3.077 |
| R-HSA-5358351 | Signaling by Hedgehog | 8.422664e-04 | 3.075 |
| R-HSA-3371511 | HSF1 activation | 8.529619e-04 | 3.069 |
| R-HSA-70263 | Gluconeogenesis | 9.459741e-04 | 3.024 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 9.666848e-04 | 3.015 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 1.026157e-03 | 2.989 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 1.115128e-03 | 2.953 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 1.115128e-03 | 2.953 |
| R-HSA-9766229 | Degradation of CDH1 | 1.115128e-03 | 2.953 |
| R-HSA-199991 | Membrane Trafficking | 1.169596e-03 | 2.932 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 1.195364e-03 | 2.922 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 1.259386e-03 | 2.900 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 1.269897e-03 | 2.896 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 1.308947e-03 | 2.883 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 1.344990e-03 | 2.871 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.425571e-03 | 2.846 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 1.438335e-03 | 2.842 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 1.530154e-03 | 2.815 |
| R-HSA-9020956 | Interleukin-27 signaling | 1.503598e-03 | 2.823 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 1.652423e-03 | 2.782 |
| R-HSA-9824272 | Somitogenesis | 1.666264e-03 | 2.778 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 1.783783e-03 | 2.749 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 1.803703e-03 | 2.744 |
| R-HSA-168256 | Immune System | 1.830592e-03 | 2.737 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 1.840094e-03 | 2.735 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 1.864883e-03 | 2.729 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 1.947719e-03 | 2.710 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.955956e-03 | 2.709 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.955956e-03 | 2.709 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.955956e-03 | 2.709 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.955956e-03 | 2.709 |
| R-HSA-166520 | Signaling by NTRKs | 2.233812e-03 | 2.651 |
| R-HSA-169911 | Regulation of Apoptosis | 2.240219e-03 | 2.650 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 2.240219e-03 | 2.650 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 2.264627e-03 | 2.645 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 2.388175e-03 | 2.622 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 2.398357e-03 | 2.620 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 2.618663e-03 | 2.582 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 2.495311e-03 | 2.603 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 2.779084e-03 | 2.556 |
| R-HSA-202403 | TCR signaling | 2.911440e-03 | 2.536 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 3.041986e-03 | 2.517 |
| R-HSA-5633007 | Regulation of TP53 Activity | 3.066472e-03 | 2.513 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 3.122130e-03 | 2.506 |
| R-HSA-4641257 | Degradation of AXIN | 3.174429e-03 | 2.498 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 3.293562e-03 | 2.482 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 3.362881e-03 | 2.473 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 3.362881e-03 | 2.473 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 3.521345e-03 | 2.453 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 3.521345e-03 | 2.453 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 3.568398e-03 | 2.448 |
| R-HSA-9909396 | Circadian clock | 3.647240e-03 | 2.438 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 3.674805e-03 | 2.435 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 4.370839e-03 | 2.359 |
| R-HSA-444257 | RSK activation | 3.912968e-03 | 2.407 |
| R-HSA-6798695 | Neutrophil degranulation | 3.946733e-03 | 2.404 |
| R-HSA-8984722 | Interleukin-35 Signalling | 4.149548e-03 | 2.382 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 4.422742e-03 | 2.354 |
| R-HSA-9907900 | Proteasome assembly | 3.980558e-03 | 2.400 |
| R-HSA-9854909 | Regulation of MITF-M dependent genes involved in invasion | 4.370839e-03 | 2.359 |
| R-HSA-1234174 | Cellular response to hypoxia | 4.063474e-03 | 2.391 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 4.217425e-03 | 2.375 |
| R-HSA-69481 | G2/M Checkpoints | 4.298260e-03 | 2.367 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 4.398413e-03 | 2.357 |
| R-HSA-69541 | Stabilization of p53 | 4.398413e-03 | 2.357 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 4.446075e-03 | 2.352 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 4.672161e-03 | 2.330 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 4.691103e-03 | 2.329 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 4.759574e-03 | 2.322 |
| R-HSA-390522 | Striated Muscle Contraction | 4.778694e-03 | 2.321 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 4.778694e-03 | 2.321 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 5.610443e-03 | 2.251 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 5.610443e-03 | 2.251 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 5.970715e-03 | 2.224 |
| R-HSA-450294 | MAP kinase activation | 5.981746e-03 | 2.223 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 5.970715e-03 | 2.224 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 5.970715e-03 | 2.224 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 5.795583e-03 | 2.237 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 5.434923e-03 | 2.265 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 5.981746e-03 | 2.223 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 5.610443e-03 | 2.251 |
| R-HSA-9711123 | Cellular response to chemical stress | 5.394877e-03 | 2.268 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 5.327544e-03 | 2.273 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 5.137184e-03 | 2.289 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 5.643171e-03 | 2.248 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 5.643171e-03 | 2.248 |
| R-HSA-112315 | Transmission across Chemical Synapses | 6.035108e-03 | 2.219 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 6.104762e-03 | 2.214 |
| R-HSA-162906 | HIV Infection | 6.176829e-03 | 2.209 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 6.219718e-03 | 2.206 |
| R-HSA-446343 | Localization of the PINCH-ILK-PARVIN complex to focal adhesions | 6.397442e-03 | 2.194 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 6.504884e-03 | 2.187 |
| R-HSA-195721 | Signaling by WNT | 6.559232e-03 | 2.183 |
| R-HSA-187687 | Signalling to ERKs | 6.625102e-03 | 2.179 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 6.625102e-03 | 2.179 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 6.737049e-03 | 2.172 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 6.903481e-03 | 2.161 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 6.938481e-03 | 2.159 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 6.938481e-03 | 2.159 |
| R-HSA-9609690 | HCMV Early Events | 7.098835e-03 | 2.149 |
| R-HSA-72172 | mRNA Splicing | 7.304276e-03 | 2.136 |
| R-HSA-2408522 | Selenoamino acid metabolism | 7.476238e-03 | 2.126 |
| R-HSA-6783589 | Interleukin-6 family signaling | 7.654380e-03 | 2.116 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 7.654380e-03 | 2.116 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 7.663841e-03 | 2.116 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 7.770374e-03 | 2.110 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 9.252044e-03 | 2.034 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 9.252044e-03 | 2.034 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 9.252044e-03 | 2.034 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 8.982095e-03 | 2.047 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 8.982059e-03 | 2.047 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 7.815041e-03 | 2.107 |
| R-HSA-4839726 | Chromatin organization | 8.052822e-03 | 2.094 |
| R-HSA-3247509 | Chromatin modifying enzymes | 9.249349e-03 | 2.034 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 7.770374e-03 | 2.110 |
| R-HSA-74749 | Signal attenuation | 7.770374e-03 | 2.110 |
| R-HSA-68875 | Mitotic Prophase | 8.304977e-03 | 2.081 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 9.230393e-03 | 2.035 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 9.120804e-03 | 2.040 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 8.852114e-03 | 2.053 |
| R-HSA-111996 | Ca-dependent events | 7.954238e-03 | 2.099 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 7.770374e-03 | 2.110 |
| R-HSA-8853659 | RET signaling | 7.734628e-03 | 2.112 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 7.734628e-03 | 2.112 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 8.982095e-03 | 2.047 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 8.892521e-03 | 2.051 |
| R-HSA-140342 | Apoptosis induced DNA fragmentation | 7.770374e-03 | 2.110 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 1.023007e-02 | 1.990 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 1.023007e-02 | 1.990 |
| R-HSA-9679506 | SARS-CoV Infections | 1.029054e-02 | 1.988 |
| R-HSA-164944 | Nef and signal transduction | 1.034466e-02 | 1.985 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 1.034466e-02 | 1.985 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 1.041520e-02 | 1.982 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 1.041520e-02 | 1.982 |
| R-HSA-9013694 | Signaling by NOTCH4 | 1.102693e-02 | 1.958 |
| R-HSA-68949 | Orc1 removal from chromatin | 1.153820e-02 | 1.938 |
| R-HSA-198753 | ERK/MAPK targets | 1.162398e-02 | 1.935 |
| R-HSA-169893 | Prolonged ERK activation events | 1.166412e-02 | 1.933 |
| R-HSA-5368598 | Negative regulation of TCF-dependent signaling by DVL-interacting proteins | 1.167664e-02 | 1.933 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 1.169958e-02 | 1.932 |
| R-HSA-397014 | Muscle contraction | 1.171206e-02 | 1.931 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 1.184603e-02 | 1.926 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 1.184603e-02 | 1.926 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 1.193289e-02 | 1.923 |
| R-HSA-5663205 | Infectious disease | 1.243542e-02 | 1.905 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 1.297132e-02 | 1.887 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 1.355982e-02 | 1.868 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 1.369979e-02 | 1.863 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 1.369979e-02 | 1.863 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 1.512357e-02 | 1.820 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 1.512357e-02 | 1.820 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 1.512357e-02 | 1.820 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 1.512357e-02 | 1.820 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 1.512357e-02 | 1.820 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 1.467911e-02 | 1.833 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 1.467911e-02 | 1.833 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 1.448829e-02 | 1.839 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 1.448829e-02 | 1.839 |
| R-HSA-166208 | mTORC1-mediated signalling | 1.673154e-02 | 1.776 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.765720e-02 | 1.753 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 1.635124e-02 | 1.786 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 1.635124e-02 | 1.786 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 1.564430e-02 | 1.806 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.486906e-02 | 1.828 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 1.587388e-02 | 1.799 |
| R-HSA-373755 | Semaphorin interactions | 1.699699e-02 | 1.770 |
| R-HSA-448424 | Interleukin-17 signaling | 1.587388e-02 | 1.799 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 1.556200e-02 | 1.808 |
| R-HSA-9758941 | Gastrulation | 1.487728e-02 | 1.827 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 1.467911e-02 | 1.833 |
| R-HSA-5620924 | Intraflagellar transport | 1.704350e-02 | 1.768 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 1.640062e-02 | 1.785 |
| R-HSA-5688426 | Deubiquitination | 1.742065e-02 | 1.759 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 1.736377e-02 | 1.760 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 1.587388e-02 | 1.799 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 1.564430e-02 | 1.806 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 1.765720e-02 | 1.753 |
| R-HSA-9700206 | Signaling by ALK in cancer | 1.736377e-02 | 1.760 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 1.556200e-02 | 1.808 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 1.774346e-02 | 1.751 |
| R-HSA-2028269 | Signaling by Hippo | 1.775587e-02 | 1.751 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 1.783205e-02 | 1.749 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 1.795483e-02 | 1.746 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 1.795483e-02 | 1.746 |
| R-HSA-2559585 | Oncogene Induced Senescence | 1.795483e-02 | 1.746 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 1.824034e-02 | 1.739 |
| R-HSA-5660489 | MTF1 activates gene expression | 1.886216e-02 | 1.724 |
| R-HSA-69560 | Transcriptional activation of p53 responsive genes | 1.886216e-02 | 1.724 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 | 1.886216e-02 | 1.724 |
| R-HSA-9020702 | Interleukin-1 signaling | 1.905008e-02 | 1.720 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 1.917078e-02 | 1.717 |
| R-HSA-909733 | Interferon alpha/beta signaling | 1.970891e-02 | 1.705 |
| R-HSA-982772 | Growth hormone receptor signaling | 1.980414e-02 | 1.703 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 1.980414e-02 | 1.703 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 1.980414e-02 | 1.703 |
| R-HSA-165159 | MTOR signalling | 1.995322e-02 | 1.700 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 2.001415e-02 | 1.699 |
| R-HSA-196025 | Formation of annular gap junctions | 2.001415e-02 | 1.699 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 2.001415e-02 | 1.699 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 2.009792e-02 | 1.697 |
| R-HSA-111933 | Calmodulin induced events | 2.050405e-02 | 1.688 |
| R-HSA-111997 | CaM pathway | 2.050405e-02 | 1.688 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 2.055843e-02 | 1.687 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 2.106117e-02 | 1.677 |
| R-HSA-9609646 | HCMV Infection | 2.113397e-02 | 1.675 |
| R-HSA-72312 | rRNA processing | 2.113458e-02 | 1.675 |
| R-HSA-3928664 | Ephrin signaling | 2.149578e-02 | 1.668 |
| R-HSA-111471 | Apoptotic factor-mediated response | 2.149578e-02 | 1.668 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 2.170198e-02 | 1.664 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 2.170198e-02 | 1.664 |
| R-HSA-6807070 | PTEN Regulation | 2.196507e-02 | 1.658 |
| R-HSA-170968 | Frs2-mediated activation | 2.210016e-02 | 1.656 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 2.210016e-02 | 1.656 |
| R-HSA-9796292 | Formation of axial mesoderm | 2.210016e-02 | 1.656 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 2.240007e-02 | 1.650 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 2.305981e-02 | 1.637 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 2.342862e-02 | 1.630 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 2.393034e-02 | 1.621 |
| R-HSA-389948 | Co-inhibition by PD-1 | 2.430185e-02 | 1.614 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 2.440129e-02 | 1.613 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 2.459738e-02 | 1.609 |
| R-HSA-202424 | Downstream TCR signaling | 2.480423e-02 | 1.605 |
| R-HSA-3214858 | RMTs methylate histone arginines | 2.518749e-02 | 1.599 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 2.573423e-02 | 1.589 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 2.573423e-02 | 1.589 |
| R-HSA-392517 | Rap1 signalling | 2.573423e-02 | 1.589 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 3.203465e-02 | 1.494 |
| R-HSA-74713 | IRS activation | 2.800991e-02 | 1.553 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 2.640421e-02 | 1.578 |
| R-HSA-9613354 | Lipophagy | 2.640421e-02 | 1.578 |
| R-HSA-190873 | Gap junction degradation | 2.640421e-02 | 1.578 |
| R-HSA-201688 | WNT mediated activation of DVL | 2.640421e-02 | 1.578 |
| R-HSA-2025928 | Calcineurin activates NFAT | 2.640421e-02 | 1.578 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 2.732743e-02 | 1.563 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 3.328004e-02 | 1.478 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 3.087873e-02 | 1.510 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 3.498894e-02 | 1.456 |
| R-HSA-111458 | Formation of apoptosome | 3.388600e-02 | 1.470 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 2.708812e-02 | 1.567 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 2.708812e-02 | 1.567 |
| R-HSA-525793 | Myogenesis | 3.133543e-02 | 1.504 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 3.388600e-02 | 1.470 |
| R-HSA-451927 | Interleukin-2 family signaling | 3.332388e-02 | 1.477 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 2.711205e-02 | 1.567 |
| R-HSA-9856872 | Malate-aspartate shuttle | 2.732743e-02 | 1.563 |
| R-HSA-9620244 | Long-term potentiation | 2.708812e-02 | 1.567 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 2.923057e-02 | 1.534 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 2.970331e-02 | 1.527 |
| R-HSA-9006936 | Signaling by TGFB family members | 2.896149e-02 | 1.538 |
| R-HSA-8876725 | Protein methylation | 3.328004e-02 | 1.478 |
| R-HSA-202433 | Generation of second messenger molecules | 3.332388e-02 | 1.477 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 3.436935e-02 | 1.464 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 3.328004e-02 | 1.478 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 3.087873e-02 | 1.510 |
| R-HSA-445144 | Signal transduction by L1 | 3.049436e-02 | 1.516 |
| R-HSA-1280218 | Adaptive Immune System | 3.402875e-02 | 1.468 |
| R-HSA-1489509 | DAG and IP3 signaling | 2.814478e-02 | 1.551 |
| R-HSA-446652 | Interleukin-1 family signaling | 3.027103e-02 | 1.519 |
| R-HSA-69239 | Synthesis of DNA | 3.174913e-02 | 1.498 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 2.693390e-02 | 1.570 |
| R-HSA-9733709 | Cardiogenesis | 3.087873e-02 | 1.510 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 3.226902e-02 | 1.491 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 3.125174e-02 | 1.505 |
| R-HSA-381070 | IRE1alpha activates chaperones | 2.897592e-02 | 1.538 |
| R-HSA-112316 | Neuronal System | 3.557633e-02 | 1.449 |
| R-HSA-9837999 | Mitochondrial protein degradation | 3.617753e-02 | 1.442 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 3.723826e-02 | 1.429 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 3.798977e-02 | 1.420 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 3.848250e-02 | 1.415 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 3.911288e-02 | 1.408 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 3.911288e-02 | 1.408 |
| R-HSA-163358 | PKA-mediated phosphorylation of key metabolic factors | 3.911288e-02 | 1.408 |
| R-HSA-111457 | Release of apoptotic factors from the mitochondria | 3.911288e-02 | 1.408 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 3.911288e-02 | 1.408 |
| R-HSA-69242 | S Phase | 3.964206e-02 | 1.402 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 3.997985e-02 | 1.398 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 4.011500e-02 | 1.397 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 4.165553e-02 | 1.380 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 4.165553e-02 | 1.380 |
| R-HSA-5693538 | Homology Directed Repair | 4.227470e-02 | 1.374 |
| R-HSA-9020558 | Interleukin-2 signaling | 4.247918e-02 | 1.372 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 4.247918e-02 | 1.372 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 4.271558e-02 | 1.369 |
| R-HSA-1236974 | ER-Phagosome pathway | 4.299788e-02 | 1.367 |
| R-HSA-5653656 | Vesicle-mediated transport | 4.375568e-02 | 1.359 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 4.423920e-02 | 1.354 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 4.428359e-02 | 1.354 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 4.598291e-02 | 1.337 |
| R-HSA-157118 | Signaling by NOTCH | 4.620595e-02 | 1.335 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 4.666214e-02 | 1.331 |
| R-HSA-9615710 | Late endosomal microautophagy | 4.667568e-02 | 1.331 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 4.667568e-02 | 1.331 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 4.667568e-02 | 1.331 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 4.744169e-02 | 1.324 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 4.744169e-02 | 1.324 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 4.744169e-02 | 1.324 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 4.744169e-02 | 1.324 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 4.744169e-02 | 1.324 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 4.808565e-02 | 1.318 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 4.894043e-02 | 1.310 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 4.894647e-02 | 1.310 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 4.948654e-02 | 1.306 |
| R-HSA-5693606 | DNA Double Strand Break Response | 5.005735e-02 | 1.301 |
| R-HSA-1433557 | Signaling by SCF-KIT | 5.082814e-02 | 1.294 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 5.093283e-02 | 1.293 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 5.093283e-02 | 1.293 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 5.093283e-02 | 1.293 |
| R-HSA-69306 | DNA Replication | 5.166668e-02 | 1.287 |
| R-HSA-9842640 | Signaling by LTK in cancer | 5.211517e-02 | 1.283 |
| R-HSA-8951671 | RUNX3 regulates YAP1-mediated transcription | 5.211517e-02 | 1.283 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 5.211517e-02 | 1.283 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 5.218750e-02 | 1.282 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 5.218750e-02 | 1.282 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 5.269248e-02 | 1.278 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 5.364048e-02 | 1.271 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 5.364048e-02 | 1.271 |
| R-HSA-194306 | Neurophilin interactions with VEGF and VEGFR | 5.364048e-02 | 1.271 |
| R-HSA-198765 | Signalling to ERK5 | 5.364048e-02 | 1.271 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 5.364048e-02 | 1.271 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 5.364048e-02 | 1.271 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 5.364048e-02 | 1.271 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 5.364048e-02 | 1.271 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 5.364048e-02 | 1.271 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 5.364048e-02 | 1.271 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 5.364048e-02 | 1.271 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 5.364048e-02 | 1.271 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 5.364048e-02 | 1.271 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 5.364048e-02 | 1.271 |
| R-HSA-1500620 | Meiosis | 5.491463e-02 | 1.260 |
| R-HSA-1227986 | Signaling by ERBB2 | 5.528388e-02 | 1.257 |
| R-HSA-72187 | mRNA 3'-end processing | 5.596277e-02 | 1.252 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 5.596277e-02 | 1.252 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 5.596277e-02 | 1.252 |
| R-HSA-73857 | RNA Polymerase II Transcription | 5.778737e-02 | 1.238 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 5.882422e-02 | 1.230 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 5.883368e-02 | 1.230 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 5.917414e-02 | 1.228 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 5.917414e-02 | 1.228 |
| R-HSA-9674415 | Drug resistance of PDGFR mutants | 8.832354e-02 | 1.054 |
| R-HSA-9674428 | PDGFR mutants bind TKIs | 8.832354e-02 | 1.054 |
| R-HSA-9674396 | Imatinib-resistant PDGFR mutants | 8.832354e-02 | 1.054 |
| R-HSA-9674401 | Sunitinib-resistant PDGFR mutants | 8.832354e-02 | 1.054 |
| R-HSA-9674404 | Sorafenib-resistant PDGFR mutants | 8.832354e-02 | 1.054 |
| R-HSA-9674403 | Regorafenib-resistant PDGFR mutants | 8.832354e-02 | 1.054 |
| R-HSA-8875513 | MET interacts with TNS proteins | 7.898090e-02 | 1.102 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 8.341809e-02 | 1.079 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 6.300003e-02 | 1.201 |
| R-HSA-877312 | Regulation of IFNG signaling | 6.300003e-02 | 1.201 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 7.489273e-02 | 1.126 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 7.489273e-02 | 1.126 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 7.489273e-02 | 1.126 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 7.489273e-02 | 1.126 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 8.782994e-02 | 1.056 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 6.467622e-02 | 1.189 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 6.269009e-02 | 1.203 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 8.496746e-02 | 1.071 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 7.354775e-02 | 1.133 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 8.144184e-02 | 1.089 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 7.415151e-02 | 1.130 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 8.883763e-02 | 1.051 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 6.785892e-02 | 1.168 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 7.354775e-02 | 1.133 |
| R-HSA-3214842 | HDMs demethylate histones | 7.087134e-02 | 1.150 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 6.467622e-02 | 1.189 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 7.287968e-02 | 1.137 |
| R-HSA-8985947 | Interleukin-9 signaling | 8.341809e-02 | 1.079 |
| R-HSA-9020933 | Interleukin-23 signaling | 8.341809e-02 | 1.079 |
| R-HSA-1181150 | Signaling by NODAL | 8.496746e-02 | 1.071 |
| R-HSA-389356 | Co-stimulation by CD28 | 7.999210e-02 | 1.097 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 7.427007e-02 | 1.129 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 7.427007e-02 | 1.129 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 8.682985e-02 | 1.061 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 7.489273e-02 | 1.126 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 6.241660e-02 | 1.205 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 8.682985e-02 | 1.061 |
| R-HSA-168898 | Toll-like Receptor Cascades | 8.672663e-02 | 1.062 |
| R-HSA-442720 | CREB1 phosphorylation through the activation of Adenylate Cyclase | 7.489273e-02 | 1.126 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 7.827375e-02 | 1.106 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 7.287968e-02 | 1.137 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 6.580234e-02 | 1.182 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 8.724274e-02 | 1.059 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 8.362090e-02 | 1.078 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 7.354775e-02 | 1.133 |
| R-HSA-5689880 | Ub-specific processing proteases | 5.937071e-02 | 1.226 |
| R-HSA-3249367 | STAT6-mediated induction of chemokines | 7.898090e-02 | 1.102 |
| R-HSA-6807004 | Negative regulation of MET activity | 8.496746e-02 | 1.071 |
| R-HSA-445355 | Smooth Muscle Contraction | 6.103253e-02 | 1.214 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 6.686623e-02 | 1.175 |
| R-HSA-74160 | Gene expression (Transcription) | 6.398346e-02 | 1.194 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 7.287968e-02 | 1.137 |
| R-HSA-112043 | PLC beta mediated events | 5.996789e-02 | 1.222 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 7.287968e-02 | 1.137 |
| R-HSA-212436 | Generic Transcription Pathway | 8.219942e-02 | 1.085 |
| R-HSA-9636249 | Inhibition of nitric oxide production | 7.898090e-02 | 1.102 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 6.692371e-02 | 1.174 |
| R-HSA-9629569 | Protein hydroxylation | 8.496746e-02 | 1.071 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 8.129788e-02 | 1.090 |
| R-HSA-8848021 | Signaling by PTK6 | 7.009991e-02 | 1.154 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 7.009991e-02 | 1.154 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 7.036859e-02 | 1.153 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 6.269009e-02 | 1.203 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 8.631124e-02 | 1.064 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 8.898209e-02 | 1.051 |
| R-HSA-8863678 | Neurodegenerative Diseases | 6.269009e-02 | 1.203 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 6.269009e-02 | 1.203 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 8.898209e-02 | 1.051 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 6.739902e-02 | 1.171 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 6.977765e-02 | 1.156 |
| R-HSA-8963896 | HDL assembly | 8.782994e-02 | 1.056 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 8.496746e-02 | 1.071 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 5.996789e-02 | 1.222 |
| R-HSA-5632684 | Hedgehog 'on' state | 6.785892e-02 | 1.168 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 8.980512e-02 | 1.047 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 8.980512e-02 | 1.047 |
| R-HSA-180746 | Nuclear import of Rev protein | 8.980512e-02 | 1.047 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 8.980512e-02 | 1.047 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 9.073347e-02 | 1.042 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 9.130475e-02 | 1.040 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 9.176770e-02 | 1.037 |
| R-HSA-112040 | G-protein mediated events | 9.348045e-02 | 1.029 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 9.414370e-02 | 1.026 |
| R-HSA-109582 | Hemostasis | 9.611721e-02 | 1.017 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 9.622734e-02 | 1.017 |
| R-HSA-382556 | ABC-family proteins mediated transport | 9.718304e-02 | 1.012 |
| R-HSA-194441 | Metabolism of non-coding RNA | 9.758247e-02 | 1.011 |
| R-HSA-191859 | snRNP Assembly | 9.758247e-02 | 1.011 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 9.863307e-02 | 1.006 |
| R-HSA-77387 | Insulin receptor recycling | 9.889725e-02 | 1.005 |
| R-HSA-5620971 | Pyroptosis | 9.889725e-02 | 1.005 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 9.889725e-02 | 1.005 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 9.889725e-02 | 1.005 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 1.002117e-01 | 0.999 |
| R-HSA-9020958 | Interleukin-21 signaling | 1.014586e-01 | 0.994 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 1.014586e-01 | 0.994 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 1.014586e-01 | 0.994 |
| R-HSA-8851680 | Butyrophilin (BTN) family interactions | 1.014586e-01 | 0.994 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 1.017660e-01 | 0.992 |
| R-HSA-418885 | DCC mediated attractive signaling | 1.017660e-01 | 0.992 |
| R-HSA-1502540 | Signaling by Activin | 1.017660e-01 | 0.992 |
| R-HSA-171007 | p38MAPK events | 1.017660e-01 | 0.992 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 1.047040e-01 | 0.980 |
| R-HSA-351202 | Metabolism of polyamines | 1.047040e-01 | 0.980 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 1.050877e-01 | 0.978 |
| R-HSA-9679191 | Potential therapeutics for SARS | 1.061714e-01 | 0.974 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 1.067404e-01 | 0.972 |
| R-HSA-8952158 | RUNX3 regulates BCL2L11 (BIM) transcription | 1.072286e-01 | 0.970 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 1.072286e-01 | 0.970 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 1.072286e-01 | 0.970 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 1.072286e-01 | 0.970 |
| R-HSA-390651 | Dopamine receptors | 1.072286e-01 | 0.970 |
| R-HSA-8941326 | RUNX2 regulates bone development | 1.079191e-01 | 0.967 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 1.082020e-01 | 0.966 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 1.093706e-01 | 0.961 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 1.121170e-01 | 0.950 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 1.137602e-01 | 0.944 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 1.137602e-01 | 0.944 |
| R-HSA-114608 | Platelet degranulation | 1.158639e-01 | 0.936 |
| R-HSA-176412 | Phosphorylation of the APC/C | 1.166468e-01 | 0.933 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 1.166468e-01 | 0.933 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 1.166468e-01 | 0.933 |
| R-HSA-9664420 | Killing mechanisms | 1.166468e-01 | 0.933 |
| R-HSA-9634600 | Regulation of glycolysis by fructose 2,6-bisphosphate metabolism | 1.166468e-01 | 0.933 |
| R-HSA-1221632 | Meiotic synapsis | 1.175419e-01 | 0.930 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 1.175419e-01 | 0.930 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 1.176544e-01 | 0.929 |
| R-HSA-9707616 | Heme signaling | 1.198185e-01 | 0.921 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 1.203872e-01 | 0.919 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 1.203872e-01 | 0.919 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 1.203872e-01 | 0.919 |
| R-HSA-350054 | Notch-HLH transcription pathway | 1.208644e-01 | 0.918 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 1.208644e-01 | 0.918 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 1.208644e-01 | 0.918 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 1.208644e-01 | 0.918 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 1.208644e-01 | 0.918 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 1.208930e-01 | 0.918 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 1.208930e-01 | 0.918 |
| R-HSA-9762292 | Regulation of CDH11 function | 1.208930e-01 | 0.918 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 1.208930e-01 | 0.918 |
| R-HSA-2586552 | Signaling by Leptin | 1.208930e-01 | 0.918 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 1.208930e-01 | 0.918 |
| R-HSA-9683686 | Maturation of spike protein | 1.208930e-01 | 0.918 |
| R-HSA-6806834 | Signaling by MET | 1.214804e-01 | 0.915 |
| R-HSA-73887 | Death Receptor Signaling | 1.253472e-01 | 0.902 |
| R-HSA-8875878 | MET promotes cell motility | 1.278284e-01 | 0.893 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 1.278284e-01 | 0.893 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 1.278284e-01 | 0.893 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 1.278284e-01 | 0.893 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 1.286041e-01 | 0.891 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 1.305652e-01 | 0.884 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 1.319292e-01 | 0.880 |
| R-HSA-399719 | Trafficking of AMPA receptors | 1.319292e-01 | 0.880 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 1.319292e-01 | 0.880 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 1.319292e-01 | 0.880 |
| R-HSA-162588 | Budding and maturation of HIV virion | 1.319292e-01 | 0.880 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 1.323144e-01 | 0.878 |
| R-HSA-9675135 | Diseases of DNA repair | 1.323144e-01 | 0.878 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 1.324115e-01 | 0.878 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 1.324115e-01 | 0.878 |
| R-HSA-9675151 | Disorders of Developmental Biology | 1.324115e-01 | 0.878 |
| R-HSA-3000170 | Syndecan interactions | 1.341834e-01 | 0.872 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.341834e-01 | 0.872 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 1.360719e-01 | 0.866 |
| R-HSA-4086398 | Ca2+ pathway | 1.363502e-01 | 0.865 |
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN | 1.376730e-01 | 0.861 |
| R-HSA-3134963 | DEx/H-box helicases activate type I IFN and inflammatory cytokines production | 1.376730e-01 | 0.861 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 1.376730e-01 | 0.861 |
| R-HSA-9673768 | Signaling by membrane-tethered fusions of PDGFRA or PDGFRB | 1.376730e-01 | 0.861 |
| R-HSA-426496 | Post-transcriptional silencing by small RNAs | 1.376730e-01 | 0.861 |
| R-HSA-8939245 | RUNX1 regulates transcription of genes involved in BCR signaling | 1.376730e-01 | 0.861 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 1.384288e-01 | 0.859 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 1.384288e-01 | 0.859 |
| R-HSA-114294 | Activation, translocation and oligomerization of BAX | 1.688508e-01 | 0.772 |
| R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 1.688508e-01 | 0.772 |
| R-HSA-5632987 | Defective Mismatch Repair Associated With PMS2 | 1.688508e-01 | 0.772 |
| R-HSA-5657560 | Hereditary fructose intolerance | 1.688508e-01 | 0.772 |
| R-HSA-9663199 | Defective DNA double strand break response due to BRCA1 loss of function | 1.688508e-01 | 0.772 |
| R-HSA-9709275 | Impaired BRCA2 translocation to the nucleus | 1.688508e-01 | 0.772 |
| R-HSA-9763198 | Impaired BRCA2 binding to SEM1 (DSS1) | 1.688508e-01 | 0.772 |
| R-HSA-9699150 | Defective DNA double strand break response due to BARD1 loss of function | 1.688508e-01 | 0.772 |
| R-HSA-5545483 | Defective Mismatch Repair Associated With MLH1 | 1.688508e-01 | 0.772 |
| R-HSA-5602566 | TICAM1 deficiency - HSE | 1.688508e-01 | 0.772 |
| R-HSA-176034 | Interactions of Tat with host cellular proteins | 2.422696e-01 | 0.616 |
| R-HSA-5602571 | TRAF3 deficiency - HSE | 2.422696e-01 | 0.616 |
| R-HSA-4085023 | Defective GFPT1 causes CMSTA1 | 2.422696e-01 | 0.616 |
| R-HSA-5603027 | IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... | 2.422696e-01 | 0.616 |
| R-HSA-3304347 | Loss of Function of SMAD4 in Cancer | 2.422696e-01 | 0.616 |
| R-HSA-5619039 | Defective SLC12A6 causes agenesis of the corpus callosum, with peripheral neurop... | 2.422696e-01 | 0.616 |
| R-HSA-5619054 | Defective SLC4A4 causes renal tubular acidosis, proximal, with ocular abnormalit... | 2.422696e-01 | 0.616 |
| R-HSA-5619101 | Variant SLC6A20 contributes towards hyperglycinuria (HG) and iminoglycinuria (IG... | 2.422696e-01 | 0.616 |
| R-HSA-3315487 | SMAD2/3 MH2 Domain Mutants in Cancer | 2.422696e-01 | 0.616 |
| R-HSA-5619111 | Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1) | 2.422696e-01 | 0.616 |
| R-HSA-9630794 | Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... | 2.422696e-01 | 0.616 |
| R-HSA-5602636 | IKBKB deficiency causes SCID | 2.422696e-01 | 0.616 |
| R-HSA-5609974 | Defective PGM1 causes PGM1-CDG | 2.422696e-01 | 0.616 |
| R-HSA-5660686 | Variant SLC6A20 contributes towards hyperglycinuria (HG) and iminoglycinuria (IG... | 2.422696e-01 | 0.616 |
| R-HSA-9632700 | Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... | 2.422696e-01 | 0.616 |
| R-HSA-3311021 | SMAD4 MH2 Domain Mutants in Cancer | 2.422696e-01 | 0.616 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 1.697064e-01 | 0.770 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 2.028111e-01 | 0.693 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 2.028111e-01 | 0.693 |
| R-HSA-3595172 | Defective CHST3 causes SEDCJD | 2.028111e-01 | 0.693 |
| R-HSA-3595174 | Defective CHST14 causes EDS, musculocontractural type | 2.028111e-01 | 0.693 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 1.415618e-01 | 0.849 |
| R-HSA-2514853 | Condensation of Prometaphase Chromosomes | 1.633028e-01 | 0.787 |
| R-HSA-202670 | ERKs are inactivated | 1.633028e-01 | 0.787 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 2.365483e-01 | 0.626 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 2.365483e-01 | 0.626 |
| R-HSA-3595177 | Defective CHSY1 causes TPBS | 2.365483e-01 | 0.626 |
| R-HSA-114516 | Disinhibition of SNARE formation | 2.365483e-01 | 0.626 |
| R-HSA-112412 | SOS-mediated signalling | 2.365483e-01 | 0.626 |
| R-HSA-72731 | Recycling of eIF2:GDP | 2.365483e-01 | 0.626 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 2.365483e-01 | 0.626 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 1.859545e-01 | 0.731 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 1.489933e-01 | 0.827 |
| R-HSA-446107 | Type I hemidesmosome assembly | 2.705483e-01 | 0.568 |
| R-HSA-111995 | phospho-PLA2 pathway | 2.705483e-01 | 0.568 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 2.705483e-01 | 0.568 |
| R-HSA-5652227 | Fructose biosynthesis | 2.705483e-01 | 0.568 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 2.705483e-01 | 0.568 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 2.705483e-01 | 0.568 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 1.663219e-01 | 0.779 |
| R-HSA-429947 | Deadenylation of mRNA | 1.481240e-01 | 0.829 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 1.843235e-01 | 0.734 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 1.843235e-01 | 0.734 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 2.333635e-01 | 0.632 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 2.333635e-01 | 0.632 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 2.029228e-01 | 0.693 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 2.029228e-01 | 0.693 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 2.029228e-01 | 0.693 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 2.029228e-01 | 0.693 |
| R-HSA-9027284 | Erythropoietin activates RAS | 2.578230e-01 | 0.589 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 2.578230e-01 | 0.589 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 1.777155e-01 | 0.750 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 1.565058e-01 | 0.805 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 1.565058e-01 | 0.805 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.932832e-01 | 0.714 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 1.932832e-01 | 0.714 |
| R-HSA-8949613 | Cristae formation | 1.932832e-01 | 0.714 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 1.494412e-01 | 0.826 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 2.416103e-01 | 0.617 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 2.416103e-01 | 0.617 |
| R-HSA-5673000 | RAF activation | 1.829122e-01 | 0.738 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 1.608500e-01 | 0.794 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 2.257413e-01 | 0.646 |
| R-HSA-5334118 | DNA methylation | 2.257413e-01 | 0.646 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 2.425402e-01 | 0.615 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 1.788580e-01 | 0.747 |
| R-HSA-3214815 | HDACs deacetylate histones | 2.320492e-01 | 0.634 |
| R-HSA-397795 | G-protein beta:gamma signalling | 1.565058e-01 | 0.805 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 1.799840e-01 | 0.745 |
| R-HSA-9823730 | Formation of definitive endoderm | 2.029228e-01 | 0.693 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 2.416103e-01 | 0.617 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 1.859545e-01 | 0.731 |
| R-HSA-2424491 | DAP12 signaling | 2.425402e-01 | 0.615 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 2.522086e-01 | 0.598 |
| R-HSA-9839394 | TGFBR3 expression | 1.626482e-01 | 0.789 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 2.436182e-01 | 0.613 |
| R-HSA-182971 | EGFR downregulation | 2.596572e-01 | 0.586 |
| R-HSA-9734767 | Developmental Cell Lineages | 1.468630e-01 | 0.833 |
| R-HSA-177929 | Signaling by EGFR | 1.439859e-01 | 0.842 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 1.626482e-01 | 0.789 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 2.254719e-01 | 0.647 |
| R-HSA-8983432 | Interleukin-15 signaling | 1.859545e-01 | 0.731 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 2.560901e-01 | 0.592 |
| R-HSA-167590 | Nef Mediated CD4 Down-regulation | 2.365483e-01 | 0.626 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 1.489933e-01 | 0.827 |
| R-HSA-3214847 | HATs acetylate histones | 1.476070e-01 | 0.831 |
| R-HSA-9634597 | GPER1 signaling | 2.640883e-01 | 0.578 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 1.694933e-01 | 0.771 |
| R-HSA-193639 | p75NTR signals via NF-kB | 2.578230e-01 | 0.589 |
| R-HSA-199920 | CREB phosphorylation | 2.028111e-01 | 0.693 |
| R-HSA-8866427 | VLDLR internalisation and degradation | 1.859545e-01 | 0.731 |
| R-HSA-164940 | Nef mediated downregulation of MHC class I complex cell surface expression | 2.705483e-01 | 0.568 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 2.578230e-01 | 0.589 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 1.494412e-01 | 0.826 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 2.416103e-01 | 0.617 |
| R-HSA-74752 | Signaling by Insulin receptor | 1.571744e-01 | 0.804 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 1.481240e-01 | 0.829 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 2.029228e-01 | 0.693 |
| R-HSA-162587 | HIV Life Cycle | 2.720599e-01 | 0.565 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 1.494412e-01 | 0.826 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 2.425402e-01 | 0.615 |
| R-HSA-164939 | Nef mediated downregulation of CD28 cell surface expression | 2.422696e-01 | 0.616 |
| R-HSA-195399 | VEGF binds to VEGFR leading to receptor dimerization | 1.697064e-01 | 0.770 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 1.633028e-01 | 0.787 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 1.489933e-01 | 0.827 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 2.220438e-01 | 0.654 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 1.932832e-01 | 0.714 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 2.621584e-01 | 0.581 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 2.330862e-01 | 0.632 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 1.694933e-01 | 0.771 |
| R-HSA-114604 | GPVI-mediated activation cascade | 2.109312e-01 | 0.676 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 2.615473e-01 | 0.582 |
| R-HSA-9697154 | Disorders of Nervous System Development | 1.859545e-01 | 0.731 |
| R-HSA-9005895 | Pervasive developmental disorders | 1.859545e-01 | 0.731 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 1.859545e-01 | 0.731 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 2.333635e-01 | 0.632 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 1.932832e-01 | 0.714 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 2.231949e-01 | 0.651 |
| R-HSA-6794361 | Neurexins and neuroligins | 1.961437e-01 | 0.707 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 1.593336e-01 | 0.798 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 2.028111e-01 | 0.693 |
| R-HSA-111931 | PKA-mediated phosphorylation of CREB | 2.220438e-01 | 0.654 |
| R-HSA-1296065 | Inwardly rectifying K+ channels | 2.770459e-01 | 0.557 |
| R-HSA-6784531 | tRNA processing in the nucleus | 2.048011e-01 | 0.689 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 2.069694e-01 | 0.684 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 1.795958e-01 | 0.746 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 2.416103e-01 | 0.617 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 2.231949e-01 | 0.651 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 1.696668e-01 | 0.770 |
| R-HSA-5205647 | Mitophagy | 1.829122e-01 | 0.738 |
| R-HSA-168249 | Innate Immune System | 1.591459e-01 | 0.798 |
| R-HSA-77042 | Formation of editosomes by ADAR proteins | 1.688508e-01 | 0.772 |
| R-HSA-169131 | Inhibition of PKR | 1.688508e-01 | 0.772 |
| R-HSA-9632693 | Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects | 2.422696e-01 | 0.616 |
| R-HSA-9839397 | TGFBR3 regulates FGF2 signaling | 2.422696e-01 | 0.616 |
| R-HSA-9630750 | Evasion of Oncogene Induced Senescence Due to p16INK4A Defects | 2.422696e-01 | 0.616 |
| R-HSA-194313 | VEGF ligand-receptor interactions | 1.697064e-01 | 0.770 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 2.028111e-01 | 0.693 |
| R-HSA-428540 | Activation of RAC1 | 1.633028e-01 | 0.787 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 2.365483e-01 | 0.626 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 1.859545e-01 | 0.731 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 1.663219e-01 | 0.779 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 2.254719e-01 | 0.647 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 2.231949e-01 | 0.651 |
| R-HSA-9839373 | Signaling by TGFBR3 | 2.365802e-01 | 0.626 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 1.439859e-01 | 0.842 |
| R-HSA-5578775 | Ion homeostasis | 1.439859e-01 | 0.842 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 1.834451e-01 | 0.736 |
| R-HSA-1266695 | Interleukin-7 signaling | 1.626482e-01 | 0.789 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 1.439859e-01 | 0.842 |
| R-HSA-75893 | TNF signaling | 1.439859e-01 | 0.842 |
| R-HSA-390696 | Adrenoceptors | 2.705483e-01 | 0.568 |
| R-HSA-9617828 | FOXO-mediated transcription of cell cycle genes | 2.416103e-01 | 0.617 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 2.425402e-01 | 0.615 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 1.697064e-01 | 0.770 |
| R-HSA-447041 | CHL1 interactions | 2.365483e-01 | 0.626 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 2.705483e-01 | 0.568 |
| R-HSA-210991 | Basigin interactions | 2.220438e-01 | 0.654 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 1.694933e-01 | 0.771 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 2.728576e-01 | 0.564 |
| R-HSA-111885 | Opioid Signalling | 1.852474e-01 | 0.732 |
| R-HSA-9012852 | Signaling by NOTCH3 | 2.320492e-01 | 0.634 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 2.365483e-01 | 0.626 |
| R-HSA-211000 | Gene Silencing by RNA | 1.454081e-01 | 0.837 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 2.012607e-01 | 0.696 |
| R-HSA-352238 | Breakdown of the nuclear lamina | 2.422696e-01 | 0.616 |
| R-HSA-8935964 | RUNX1 regulates expression of components of tight junctions | 1.697064e-01 | 0.770 |
| R-HSA-8983711 | OAS antiviral response | 1.859545e-01 | 0.731 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 1.859545e-01 | 0.731 |
| R-HSA-5578768 | Physiological factors | 2.333635e-01 | 0.632 |
| R-HSA-71288 | Creatine metabolism | 2.029228e-01 | 0.693 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 1.694933e-01 | 0.771 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 1.834451e-01 | 0.736 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.777155e-01 | 0.750 |
| R-HSA-447043 | Neurofascin interactions | 2.028111e-01 | 0.693 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 2.416103e-01 | 0.617 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 1.522248e-01 | 0.818 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 1.912822e-01 | 0.718 |
| R-HSA-9669938 | Signaling by KIT in disease | 2.615473e-01 | 0.582 |
| R-HSA-9603505 | NTRK3 as a dependence receptor | 2.422696e-01 | 0.616 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 1.697064e-01 | 0.770 |
| R-HSA-8849932 | Synaptic adhesion-like molecules | 1.663219e-01 | 0.779 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 2.708449e-01 | 0.567 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 1.972762e-01 | 0.705 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 2.644378e-01 | 0.578 |
| R-HSA-391906 | Leukotriene receptors | 2.028111e-01 | 0.693 |
| R-HSA-167044 | Signalling to RAS | 2.220438e-01 | 0.654 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 2.365802e-01 | 0.626 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 2.578230e-01 | 0.589 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 2.267852e-01 | 0.644 |
| R-HSA-5619084 | ABC transporter disorders | 1.788580e-01 | 0.747 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 2.109312e-01 | 0.676 |
| R-HSA-9008059 | Interleukin-37 signaling | 2.425402e-01 | 0.615 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 2.554605e-01 | 0.593 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 2.220438e-01 | 0.654 |
| R-HSA-416482 | G alpha (12/13) signalling events | 2.771140e-01 | 0.557 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 2.781642e-01 | 0.556 |
| R-HSA-912526 | Interleukin receptor SHC signaling | 2.817812e-01 | 0.550 |
| R-HSA-8854691 | Interleukin-20 family signaling | 2.817812e-01 | 0.550 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 2.817812e-01 | 0.550 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 2.826005e-01 | 0.549 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 2.826005e-01 | 0.549 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 2.826005e-01 | 0.549 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 2.826005e-01 | 0.549 |
| R-HSA-392499 | Metabolism of proteins | 2.840862e-01 | 0.547 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 2.864465e-01 | 0.543 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 2.864465e-01 | 0.543 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 2.864465e-01 | 0.543 |
| R-HSA-5696398 | Nucleotide Excision Repair | 2.911694e-01 | 0.536 |
| R-HSA-354192 | Integrin signaling | 2.946603e-01 | 0.531 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 2.946603e-01 | 0.531 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 2.946603e-01 | 0.531 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 2.983170e-01 | 0.525 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 3.022333e-01 | 0.520 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 3.022333e-01 | 0.520 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 3.022406e-01 | 0.520 |
| R-HSA-170984 | ARMS-mediated activation | 3.045017e-01 | 0.516 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 3.045017e-01 | 0.516 |
| R-HSA-9700645 | ALK mutants bind TKIs | 3.045017e-01 | 0.516 |
| R-HSA-428543 | Inactivation of CDC42 and RAC1 | 3.045017e-01 | 0.516 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 3.045017e-01 | 0.516 |
| R-HSA-418889 | Caspase activation via Dependence Receptors in the absence of ligand | 3.045017e-01 | 0.516 |
| R-HSA-176974 | Unwinding of DNA | 3.045017e-01 | 0.516 |
| R-HSA-9762293 | Regulation of CDH11 gene transcription | 3.045017e-01 | 0.516 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 3.045017e-01 | 0.516 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 3.045017e-01 | 0.516 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 3.045017e-01 | 0.516 |
| R-HSA-912446 | Meiotic recombination | 3.068407e-01 | 0.513 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 3.075680e-01 | 0.512 |
| R-HSA-4420332 | Defective B3GALT6 causes EDSP2 and SEMDJL1 | 3.075680e-01 | 0.512 |
| R-HSA-3560783 | Defective B4GALT7 causes EDS, progeroid type | 3.075680e-01 | 0.512 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 3.075680e-01 | 0.512 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 3.075680e-01 | 0.512 |
| R-HSA-1483148 | Synthesis of PG | 3.075680e-01 | 0.512 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 3.075680e-01 | 0.512 |
| R-HSA-5660526 | Response to metal ions | 3.075680e-01 | 0.512 |
| R-HSA-211736 | Stimulation of the cell death response by PAK-2p34 | 3.092069e-01 | 0.510 |
| R-HSA-376172 | DSCAM interactions | 3.092069e-01 | 0.510 |
| R-HSA-8854521 | Interaction between PHLDA1 and AURKA | 3.092069e-01 | 0.510 |
| R-HSA-8951911 | RUNX3 regulates RUNX1-mediated transcription | 3.092069e-01 | 0.510 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 3.092069e-01 | 0.510 |
| R-HSA-1296067 | Potassium transport channels | 3.092069e-01 | 0.510 |
| R-HSA-5619104 | Defective SLC12A1 causes Bartter syndrome 1 (BS1) | 3.092069e-01 | 0.510 |
| R-HSA-75064 | mRNA Editing: A to I Conversion | 3.092069e-01 | 0.510 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 3.092069e-01 | 0.510 |
| R-HSA-75102 | C6 deamination of adenosine | 3.092069e-01 | 0.510 |
| R-HSA-9675132 | Diseases of cellular response to stress | 3.092069e-01 | 0.510 |
| R-HSA-9630747 | Diseases of Cellular Senescence | 3.092069e-01 | 0.510 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 3.118760e-01 | 0.506 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 3.181736e-01 | 0.497 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 3.181736e-01 | 0.497 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 3.213936e-01 | 0.493 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.225463e-01 | 0.491 |
| R-HSA-9614085 | FOXO-mediated transcription | 3.225463e-01 | 0.491 |
| R-HSA-997272 | Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits | 3.228565e-01 | 0.491 |
| R-HSA-1296059 | G protein gated Potassium channels | 3.228565e-01 | 0.491 |
| R-HSA-1296041 | Activation of G protein gated Potassium channels | 3.228565e-01 | 0.491 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 3.228565e-01 | 0.491 |
| R-HSA-1268020 | Mitochondrial protein import | 3.230873e-01 | 0.491 |
| R-HSA-1643685 | Disease | 3.250545e-01 | 0.488 |
| R-HSA-5696400 | Dual Incision in GG-NER | 3.303862e-01 | 0.481 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 3.303862e-01 | 0.481 |
| R-HSA-392518 | Signal amplification | 3.303862e-01 | 0.481 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 3.303862e-01 | 0.481 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 3.303862e-01 | 0.481 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 3.326074e-01 | 0.478 |
| R-HSA-3560801 | Defective B3GAT3 causes JDSSDHD | 3.326074e-01 | 0.478 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 3.326074e-01 | 0.478 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 3.326074e-01 | 0.478 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 3.360578e-01 | 0.474 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 3.360578e-01 | 0.474 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 3.364619e-01 | 0.473 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 3.381517e-01 | 0.471 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 3.381517e-01 | 0.471 |
| R-HSA-198203 | PI3K/AKT activation | 3.381517e-01 | 0.471 |
| R-HSA-5140745 | WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 3.381517e-01 | 0.471 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 3.381517e-01 | 0.471 |
| R-HSA-9761174 | Formation of intermediate mesoderm | 3.381517e-01 | 0.471 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 3.435632e-01 | 0.464 |
| R-HSA-400042 | Adrenaline,noradrenaline inhibits insulin secretion | 3.435632e-01 | 0.464 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 3.435632e-01 | 0.464 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 3.441235e-01 | 0.463 |
| R-HSA-1236394 | Signaling by ERBB4 | 3.492185e-01 | 0.457 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 3.492185e-01 | 0.457 |
| R-HSA-74751 | Insulin receptor signalling cascade | 3.503057e-01 | 0.456 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 3.576101e-01 | 0.447 |
| R-HSA-418217 | G beta:gamma signalling through PLC beta | 3.576101e-01 | 0.447 |
| R-HSA-163615 | PKA activation | 3.576101e-01 | 0.447 |
| R-HSA-500657 | Presynaptic function of Kainate receptors | 3.576101e-01 | 0.447 |
| R-HSA-164378 | PKA activation in glucagon signalling | 3.576101e-01 | 0.447 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 3.576101e-01 | 0.447 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 3.576101e-01 | 0.447 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 3.642982e-01 | 0.439 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 3.642982e-01 | 0.439 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 3.642982e-01 | 0.439 |
| R-HSA-9824443 | Parasitic Infection Pathways | 3.644815e-01 | 0.438 |
| R-HSA-9658195 | Leishmania infection | 3.644815e-01 | 0.438 |
| R-HSA-418597 | G alpha (z) signalling events | 3.656272e-01 | 0.437 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 3.666035e-01 | 0.436 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 3.666035e-01 | 0.436 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 3.689568e-01 | 0.433 |
| R-HSA-209563 | Axonal growth stimulation | 3.702347e-01 | 0.432 |
| R-HSA-9944997 | Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome | 3.702347e-01 | 0.432 |
| R-HSA-392023 | Adrenaline signalling through Alpha-2 adrenergic receptor | 3.702347e-01 | 0.432 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 3.702347e-01 | 0.432 |
| R-HSA-5660862 | Defective SLC7A7 causes lysinuric protein intolerance (LPI) | 3.702347e-01 | 0.432 |
| R-HSA-9944971 | Loss of Function of KMT2D in Kabuki Syndrome | 3.702347e-01 | 0.432 |
| R-HSA-9022538 | Loss of MECP2 binding ability to 5mC-DNA | 3.702347e-01 | 0.432 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 3.702347e-01 | 0.432 |
| R-HSA-9960525 | CASP5-mediated substrate cleavage | 3.702347e-01 | 0.432 |
| R-HSA-9960519 | CASP4-mediated substrate cleavage | 3.702347e-01 | 0.432 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 3.712872e-01 | 0.430 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 3.712872e-01 | 0.430 |
| R-HSA-1483226 | Synthesis of PI | 3.712872e-01 | 0.430 |
| R-HSA-8963888 | Chylomicron assembly | 3.712872e-01 | 0.430 |
| R-HSA-192905 | vRNP Assembly | 3.712872e-01 | 0.430 |
| R-HSA-9706019 | RHOBTB3 ATPase cycle | 3.712872e-01 | 0.430 |
| R-HSA-77108 | Utilization of Ketone Bodies | 3.712872e-01 | 0.430 |
| R-HSA-9635465 | Suppression of apoptosis | 3.712872e-01 | 0.430 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 3.712872e-01 | 0.430 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 3.749157e-01 | 0.426 |
| R-HSA-193648 | NRAGE signals death through JNK | 3.804866e-01 | 0.420 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 3.804936e-01 | 0.420 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 3.824774e-01 | 0.417 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 3.824774e-01 | 0.417 |
| R-HSA-392851 | Prostacyclin signalling through prostacyclin receptor | 3.824774e-01 | 0.417 |
| R-HSA-449836 | Other interleukin signaling | 3.824774e-01 | 0.417 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 3.850024e-01 | 0.415 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 3.878268e-01 | 0.411 |
| R-HSA-9833110 | RSV-host interactions | 3.879666e-01 | 0.411 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 3.945915e-01 | 0.404 |
| R-HSA-73864 | RNA Polymerase I Transcription | 4.007601e-01 | 0.397 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 4.037364e-01 | 0.394 |
| R-HSA-2022923 | DS-GAG biosynthesis | 4.037364e-01 | 0.394 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 4.037364e-01 | 0.394 |
| R-HSA-1250342 | PI3K events in ERBB4 signaling | 4.037364e-01 | 0.394 |
| R-HSA-5693548 | Sensing of DNA Double Strand Breaks | 4.037364e-01 | 0.394 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 4.037364e-01 | 0.394 |
| R-HSA-209560 | NF-kB is activated and signals survival | 4.037364e-01 | 0.394 |
| R-HSA-162592 | Integration of provirus | 4.037364e-01 | 0.394 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 4.037364e-01 | 0.394 |
| R-HSA-5218859 | Regulated Necrosis | 4.053946e-01 | 0.392 |
| R-HSA-9006335 | Signaling by Erythropoietin | 4.056205e-01 | 0.392 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 4.056205e-01 | 0.392 |
| R-HSA-418360 | Platelet calcium homeostasis | 4.056205e-01 | 0.392 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 4.056205e-01 | 0.392 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 4.071205e-01 | 0.390 |
| R-HSA-9645723 | Diseases of programmed cell death | 4.085373e-01 | 0.389 |
| R-HSA-418346 | Platelet homeostasis | 4.100863e-01 | 0.387 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 4.102443e-01 | 0.387 |
| R-HSA-69206 | G1/S Transition | 4.209275e-01 | 0.376 |
| R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death | 4.258743e-01 | 0.371 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 4.258743e-01 | 0.371 |
| R-HSA-2644607 | Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling | 4.258743e-01 | 0.371 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 4.258743e-01 | 0.371 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 4.258743e-01 | 0.371 |
| R-HSA-5083630 | Defective LFNG causes SCDO3 | 4.258743e-01 | 0.371 |
| R-HSA-2644605 | FBXW7 Mutants and NOTCH1 in Cancer | 4.258743e-01 | 0.371 |
| R-HSA-5626978 | TNFR1-mediated ceramide production | 4.258743e-01 | 0.371 |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity | 4.258743e-01 | 0.371 |
| R-HSA-9729555 | Sensory perception of sour taste | 4.258743e-01 | 0.371 |
| R-HSA-205025 | NADE modulates death signalling | 4.258743e-01 | 0.371 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 4.258743e-01 | 0.371 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 4.261011e-01 | 0.370 |
| R-HSA-202040 | G-protein activation | 4.314599e-01 | 0.365 |
| R-HSA-392170 | ADP signalling through P2Y purinoceptor 12 | 4.314599e-01 | 0.365 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 4.314599e-01 | 0.365 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 4.314599e-01 | 0.365 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 4.329840e-01 | 0.364 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 4.353622e-01 | 0.361 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 4.353622e-01 | 0.361 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 4.353622e-01 | 0.361 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 4.353622e-01 | 0.361 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 4.353622e-01 | 0.361 |
| R-HSA-9931530 | Phosphorylation and nuclear translocation of the CRY:PER:kinase complex | 4.353622e-01 | 0.361 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 4.353622e-01 | 0.361 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 4.385277e-01 | 0.358 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 4.385277e-01 | 0.358 |
| R-HSA-5260271 | Diseases of Immune System | 4.385277e-01 | 0.358 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 4.385277e-01 | 0.358 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 4.451636e-01 | 0.351 |
| R-HSA-445717 | Aquaporin-mediated transport | 4.546651e-01 | 0.342 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 4.554254e-01 | 0.342 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 4.554254e-01 | 0.342 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 4.554254e-01 | 0.342 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 4.554254e-01 | 0.342 |
| R-HSA-175474 | Assembly Of The HIV Virion | 4.554254e-01 | 0.342 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 4.660569e-01 | 0.332 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 4.660569e-01 | 0.332 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 4.660569e-01 | 0.332 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 4.660569e-01 | 0.332 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 4.660569e-01 | 0.332 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 4.660569e-01 | 0.332 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 4.660569e-01 | 0.332 |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome | 4.660569e-01 | 0.332 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 4.693362e-01 | 0.329 |
| R-HSA-399710 | Activation of AMPA receptors | 4.766011e-01 | 0.322 |
| R-HSA-9818026 | NFE2L2 regulating inflammation associated genes | 4.766011e-01 | 0.322 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 4.766011e-01 | 0.322 |
| R-HSA-9022535 | Loss of phosphorylation of MECP2 at T308 | 4.766011e-01 | 0.322 |
| R-HSA-110381 | Resolution of AP sites via the single-nucleotide replacement pathway | 4.766011e-01 | 0.322 |
| R-HSA-8849472 | PTK6 Down-Regulation | 4.766011e-01 | 0.322 |
| R-HSA-165158 | Activation of AKT2 | 4.766011e-01 | 0.322 |
| R-HSA-8866376 | Reelin signalling pathway | 4.766011e-01 | 0.322 |
| R-HSA-9032759 | NTRK2 activates RAC1 | 4.766011e-01 | 0.322 |
| R-HSA-390648 | Muscarinic acetylcholine receptors | 4.766011e-01 | 0.322 |
| R-HSA-111464 | SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | 4.766011e-01 | 0.322 |
| R-HSA-111463 | SMAC (DIABLO) binds to IAPs | 4.766011e-01 | 0.322 |
| R-HSA-435368 | Zinc efflux and compartmentalization by the SLC30 family | 4.766011e-01 | 0.322 |
| R-HSA-168316 | Assembly of Viral Components at the Budding Site | 4.766011e-01 | 0.322 |
| R-HSA-5652084 | Fructose metabolism | 4.789553e-01 | 0.320 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 4.789553e-01 | 0.320 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 4.789553e-01 | 0.320 |
| R-HSA-8964038 | LDL clearance | 4.789553e-01 | 0.320 |
| R-HSA-9857377 | Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autopha... | 4.789553e-01 | 0.320 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 4.794705e-01 | 0.319 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 4.794705e-01 | 0.319 |
| R-HSA-1474165 | Reproduction | 4.820246e-01 | 0.317 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 4.839091e-01 | 0.315 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 4.862613e-01 | 0.313 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 4.862613e-01 | 0.313 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 4.862613e-01 | 0.313 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 4.862613e-01 | 0.313 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 4.873448e-01 | 0.312 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 4.913215e-01 | 0.309 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 4.957382e-01 | 0.305 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 4.957382e-01 | 0.305 |
| R-HSA-1433559 | Regulation of KIT signaling | 4.957382e-01 | 0.305 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 4.957382e-01 | 0.305 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 4.957382e-01 | 0.305 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 4.957382e-01 | 0.305 |
| R-HSA-9686114 | Non-canonical inflammasome activation | 4.957382e-01 | 0.305 |
| R-HSA-391160 | Signal regulatory protein family interactions | 4.957382e-01 | 0.305 |
| R-HSA-1482798 | Acyl chain remodeling of CL | 4.957382e-01 | 0.305 |
| R-HSA-9679514 | SARS-CoV-1 Genome Replication and Transcription | 4.957382e-01 | 0.305 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 4.960137e-01 | 0.305 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 5.010516e-01 | 0.300 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 5.057546e-01 | 0.296 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 5.057546e-01 | 0.296 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 5.073705e-01 | 0.295 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 5.073705e-01 | 0.295 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 5.198882e-01 | 0.284 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 5.201594e-01 | 0.284 |
| R-HSA-2660825 | Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 5.228487e-01 | 0.282 |
| R-HSA-2660826 | Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 5.228487e-01 | 0.282 |
| R-HSA-164525 | Plus-strand DNA synthesis | 5.228487e-01 | 0.282 |
| R-HSA-182218 | Nef Mediated CD8 Down-regulation | 5.228487e-01 | 0.282 |
| R-HSA-5638303 | Inhibition of Signaling by Overexpressed EGFR | 5.228487e-01 | 0.282 |
| R-HSA-111459 | Activation of caspases through apoptosome-mediated cleavage | 5.228487e-01 | 0.282 |
| R-HSA-5638302 | Signaling by Overexpressed Wild-Type EGFR in Cancer | 5.228487e-01 | 0.282 |
| R-HSA-9017802 | Noncanonical activation of NOTCH3 | 5.228487e-01 | 0.282 |
| R-HSA-9865113 | Loss-of-function mutations in DBT cause MSUD2 | 5.228487e-01 | 0.282 |
| R-HSA-9652817 | Signaling by MAPK mutants | 5.228487e-01 | 0.282 |
| R-HSA-4341670 | Defective NEU1 causes sialidosis | 5.228487e-01 | 0.282 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 5.228487e-01 | 0.282 |
| R-HSA-9907570 | Loss-of-function mutations in DLD cause MSUD3/DLDD | 5.228487e-01 | 0.282 |
| R-HSA-166665 | Terminal pathway of complement | 5.228487e-01 | 0.282 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 5.228487e-01 | 0.282 |
| R-HSA-187706 | Signalling to p38 via RIT and RIN | 5.228487e-01 | 0.282 |
| R-HSA-111469 | SMAC, XIAP-regulated apoptotic response | 5.228487e-01 | 0.282 |
| R-HSA-9758919 | Epithelial-Mesenchymal Transition (EMT) during gastrulation | 5.228487e-01 | 0.282 |
| R-HSA-9860276 | SLC15A4:TASL-dependent IRF5 activation | 5.228487e-01 | 0.282 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 5.243455e-01 | 0.280 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 5.243455e-01 | 0.280 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 5.243455e-01 | 0.280 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 5.243455e-01 | 0.280 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 5.243455e-01 | 0.280 |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment | 5.243455e-01 | 0.280 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 5.243455e-01 | 0.280 |
| R-HSA-9823739 | Formation of the anterior neural plate | 5.243455e-01 | 0.280 |
| R-HSA-416700 | Other semaphorin interactions | 5.243455e-01 | 0.280 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 5.243455e-01 | 0.280 |
| R-HSA-419408 | Lysosphingolipid and LPA receptors | 5.243455e-01 | 0.280 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 5.245031e-01 | 0.280 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 5.245031e-01 | 0.280 |
| R-HSA-428930 | Thromboxane signalling through TP receptor | 5.245031e-01 | 0.280 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 5.245031e-01 | 0.280 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 5.249110e-01 | 0.280 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 5.249110e-01 | 0.280 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 5.249110e-01 | 0.280 |
| R-HSA-2172127 | DAP12 interactions | 5.254881e-01 | 0.279 |
| R-HSA-373752 | Netrin-1 signaling | 5.254881e-01 | 0.279 |
| R-HSA-375280 | Amine ligand-binding receptors | 5.254881e-01 | 0.279 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 5.313376e-01 | 0.275 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 5.313376e-01 | 0.275 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 5.313376e-01 | 0.275 |
| R-HSA-73894 | DNA Repair | 5.326278e-01 | 0.274 |
| R-HSA-3000157 | Laminin interactions | 5.464373e-01 | 0.262 |
| R-HSA-420029 | Tight junction interactions | 5.464373e-01 | 0.262 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 5.464373e-01 | 0.262 |
| R-HSA-9830364 | Formation of the nephric duct | 5.464373e-01 | 0.262 |
| R-HSA-163685 | Integration of energy metabolism | 5.516733e-01 | 0.258 |
| R-HSA-399955 | SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 5.518370e-01 | 0.258 |
| R-HSA-9942503 | Differentiation of naive CD+ T cells to T helper 1 cells (Th1 cells) | 5.518370e-01 | 0.258 |
| R-HSA-9945266 | Differentiation of T cells | 5.518370e-01 | 0.258 |
| R-HSA-71262 | Carnitine synthesis | 5.518370e-01 | 0.258 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 5.518370e-01 | 0.258 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 5.518370e-01 | 0.258 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 5.536470e-01 | 0.257 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 5.586113e-01 | 0.253 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 5.586113e-01 | 0.253 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 5.586113e-01 | 0.253 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 5.621015e-01 | 0.250 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 5.621015e-01 | 0.250 |
| R-HSA-74158 | RNA Polymerase III Transcription | 5.621015e-01 | 0.250 |
| R-HSA-163560 | Triglyceride catabolism | 5.621015e-01 | 0.250 |
| R-HSA-8964026 | Chylomicron clearance | 5.650124e-01 | 0.248 |
| R-HSA-9645135 | STAT5 Activation | 5.650124e-01 | 0.248 |
| R-HSA-162585 | Uncoating of the HIV Virion | 5.650124e-01 | 0.248 |
| R-HSA-9912481 | Branched-chain ketoacid dehydrogenase kinase deficiency | 5.650124e-01 | 0.248 |
| R-HSA-9912529 | H139Hfs13* PPM1K causes a mild variant of MSUD | 5.650124e-01 | 0.248 |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants | 5.650124e-01 | 0.248 |
| R-HSA-389542 | NADPH regeneration | 5.650124e-01 | 0.248 |
| R-HSA-8866423 | VLDL assembly | 5.650124e-01 | 0.248 |
| R-HSA-8874081 | MET activates PTK2 signaling | 5.677674e-01 | 0.246 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 5.677674e-01 | 0.246 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 5.677674e-01 | 0.246 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 5.677674e-01 | 0.246 |
| R-HSA-9637687 | Suppression of phagosomal maturation | 5.677674e-01 | 0.246 |
| R-HSA-877300 | Interferon gamma signaling | 5.699086e-01 | 0.244 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 5.710512e-01 | 0.243 |
| R-HSA-6811440 | Retrograde transport at the Trans-Golgi-Network | 5.747332e-01 | 0.241 |
| R-HSA-77595 | Processing of Intronless Pre-mRNAs | 5.781865e-01 | 0.238 |
| R-HSA-6783984 | Glycine degradation | 5.781865e-01 | 0.238 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 5.781865e-01 | 0.238 |
| R-HSA-1566977 | Fibronectin matrix formation | 5.781865e-01 | 0.238 |
| R-HSA-70370 | Galactose catabolism | 5.781865e-01 | 0.238 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 5.800886e-01 | 0.237 |
| R-HSA-204005 | COPII-mediated vesicle transport | 5.818647e-01 | 0.235 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 5.855458e-01 | 0.232 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 5.884681e-01 | 0.230 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 5.884681e-01 | 0.230 |
| R-HSA-201451 | Signaling by BMP | 5.884681e-01 | 0.230 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 5.884681e-01 | 0.230 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 5.884681e-01 | 0.230 |
| R-HSA-9031628 | NGF-stimulated transcription | 5.905399e-01 | 0.229 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 5.905399e-01 | 0.229 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 5.951203e-01 | 0.225 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 6.002811e-01 | 0.222 |
| R-HSA-5576891 | Cardiac conduction | 6.010954e-01 | 0.221 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 6.033811e-01 | 0.219 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 6.033811e-01 | 0.219 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 6.033811e-01 | 0.219 |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome | 6.033811e-01 | 0.219 |
| R-HSA-8949275 | RUNX3 Regulates Immune Response and Cell Migration | 6.034526e-01 | 0.219 |
| R-HSA-2562578 | TRIF-mediated programmed cell death | 6.034526e-01 | 0.219 |
| R-HSA-1912399 | Pre-NOTCH Processing in the Endoplasmic Reticulum | 6.034526e-01 | 0.219 |
| R-HSA-8849473 | PTK6 Expression | 6.034526e-01 | 0.219 |
| R-HSA-163754 | Insulin effects increased synthesis of Xylulose-5-Phosphate | 6.034526e-01 | 0.219 |
| R-HSA-203641 | NOSTRIN mediated eNOS trafficking | 6.034526e-01 | 0.219 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 6.034526e-01 | 0.219 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 6.034526e-01 | 0.219 |
| R-HSA-8964041 | LDL remodeling | 6.034526e-01 | 0.219 |
| R-HSA-110357 | Displacement of DNA glycosylase by APEX1 | 6.034526e-01 | 0.219 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 6.060175e-01 | 0.218 |
| R-HSA-167287 | HIV elongation arrest and recovery | 6.085199e-01 | 0.216 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 6.085199e-01 | 0.216 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 6.085199e-01 | 0.216 |
| R-HSA-451326 | Activation of kainate receptors upon glutamate binding | 6.085199e-01 | 0.216 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 6.137548e-01 | 0.212 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 6.147525e-01 | 0.211 |
| R-HSA-109704 | PI3K Cascade | 6.211537e-01 | 0.207 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 6.274192e-01 | 0.202 |
| R-HSA-73980 | RNA Polymerase III Transcription Termination | 6.274192e-01 | 0.202 |
| R-HSA-180292 | GAB1 signalosome | 6.274192e-01 | 0.202 |
| R-HSA-428643 | Organic anion transport by SLC5/17/25 transporters | 6.274192e-01 | 0.202 |
| R-HSA-432142 | Platelet sensitization by LDL | 6.274192e-01 | 0.202 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 6.274192e-01 | 0.202 |
| R-HSA-9679504 | Translation of Replicase and Assembly of the Replication Transcription Complex | 6.274192e-01 | 0.202 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 6.279084e-01 | 0.202 |
| R-HSA-180024 | DARPP-32 events | 6.279084e-01 | 0.202 |
| R-HSA-420092 | Glucagon-type ligand receptors | 6.279084e-01 | 0.202 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 6.314009e-01 | 0.200 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 6.314009e-01 | 0.200 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 6.357985e-01 | 0.197 |
| R-HSA-162589 | Reverse Transcription of HIV RNA | 6.384978e-01 | 0.195 |
| R-HSA-164516 | Minus-strand DNA synthesis | 6.384978e-01 | 0.195 |
| R-HSA-212718 | EGFR interacts with phospholipase C-gamma | 6.384978e-01 | 0.195 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 6.384978e-01 | 0.195 |
| R-HSA-8866904 | Negative regulation of activity of TFAP2 (AP-2) family transcription factors | 6.384978e-01 | 0.195 |
| R-HSA-190370 | FGFR1b ligand binding and activation | 6.384978e-01 | 0.195 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 6.384978e-01 | 0.195 |
| R-HSA-111453 | BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members | 6.384978e-01 | 0.195 |
| R-HSA-193634 | Axonal growth inhibition (RHOA activation) | 6.384978e-01 | 0.195 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 6.384978e-01 | 0.195 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 6.384978e-01 | 0.195 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 6.438717e-01 | 0.191 |
| R-HSA-8852135 | Protein ubiquitination | 6.458863e-01 | 0.190 |
| R-HSA-68962 | Activation of the pre-replicative complex | 6.466239e-01 | 0.189 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 6.466239e-01 | 0.189 |
| R-HSA-114452 | Activation of BH3-only proteins | 6.466239e-01 | 0.189 |
| R-HSA-9694548 | Maturation of spike protein | 6.475790e-01 | 0.189 |
| R-HSA-9607240 | FLT3 Signaling | 6.475790e-01 | 0.189 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 | 6.503084e-01 | 0.187 |
| R-HSA-110320 | Translesion Synthesis by POLH | 6.503084e-01 | 0.187 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 6.503084e-01 | 0.187 |
| R-HSA-9694682 | SARS-CoV-2 Genome Replication and Transcription | 6.503084e-01 | 0.187 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 6.503619e-01 | 0.187 |
| R-HSA-936837 | Ion transport by P-type ATPases | 6.539729e-01 | 0.184 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 6.618448e-01 | 0.179 |
| R-HSA-70268 | Pyruvate metabolism | 6.621601e-01 | 0.179 |
| R-HSA-9683701 | Translation of Structural Proteins | 6.632792e-01 | 0.178 |
| R-HSA-186763 | Downstream signal transduction | 6.646611e-01 | 0.177 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 6.646611e-01 | 0.177 |
| R-HSA-5694530 | Cargo concentration in the ER | 6.646611e-01 | 0.177 |
| R-HSA-5649702 | APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement P... | 6.704478e-01 | 0.174 |
| R-HSA-193697 | p75NTR regulates axonogenesis | 6.704478e-01 | 0.174 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 6.704478e-01 | 0.174 |
| R-HSA-75072 | mRNA Editing | 6.704478e-01 | 0.174 |
| R-HSA-8866907 | Activation of the TFAP2 (AP-2) family of transcription factors | 6.704478e-01 | 0.174 |
| R-HSA-9768777 | Regulation of NPAS4 gene transcription | 6.704478e-01 | 0.174 |
| R-HSA-448706 | Interleukin-1 processing | 6.704478e-01 | 0.174 |
| R-HSA-8853383 | Lysosomal oligosaccharide catabolism | 6.704478e-01 | 0.174 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 6.704478e-01 | 0.174 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 6.720639e-01 | 0.173 |
| R-HSA-163210 | Formation of ATP by chemiosmotic coupling | 6.720639e-01 | 0.173 |
| R-HSA-373753 | Nephrin family interactions | 6.720639e-01 | 0.173 |
| R-HSA-140875 | Common Pathway of Fibrin Clot Formation | 6.720639e-01 | 0.173 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 6.720639e-01 | 0.173 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 6.746402e-01 | 0.171 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 6.773230e-01 | 0.169 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 6.784961e-01 | 0.168 |
| R-HSA-991365 | Activation of GABAB receptors | 6.784961e-01 | 0.168 |
| R-HSA-977444 | GABA B receptor activation | 6.784961e-01 | 0.168 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 6.813968e-01 | 0.167 |
| R-HSA-69190 | DNA strand elongation | 6.820182e-01 | 0.166 |
| R-HSA-9664417 | Leishmania phagocytosis | 6.916131e-01 | 0.160 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 6.916131e-01 | 0.160 |
| R-HSA-9664407 | Parasite infection | 6.916131e-01 | 0.160 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 6.927074e-01 | 0.159 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 6.927074e-01 | 0.159 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 6.927074e-01 | 0.159 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 6.927074e-01 | 0.159 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 6.927074e-01 | 0.159 |
| R-HSA-5654743 | Signaling by FGFR4 | 6.932264e-01 | 0.159 |
| R-HSA-9710421 | Defective pyroptosis | 6.932264e-01 | 0.159 |
| R-HSA-73884 | Base Excision Repair | 6.946081e-01 | 0.158 |
| R-HSA-9930044 | Nuclear RNA decay | 6.986972e-01 | 0.156 |
| R-HSA-173107 | Binding and entry of HIV virion | 6.995757e-01 | 0.155 |
| R-HSA-9858328 | OADH complex synthesizes glutaryl-CoA from 2-OA | 6.995757e-01 | 0.155 |
| R-HSA-164843 | 2-LTR circle formation | 6.995757e-01 | 0.155 |
| R-HSA-68952 | DNA replication initiation | 6.995757e-01 | 0.155 |
| R-HSA-380612 | Metabolism of serotonin | 6.995757e-01 | 0.155 |
| R-HSA-9948001 | CASP4 inflammasome assembly | 6.995757e-01 | 0.155 |
| R-HSA-426048 | Arachidonate production from DAG | 6.995757e-01 | 0.155 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 6.995757e-01 | 0.155 |
| R-HSA-9664873 | Pexophagy | 6.995757e-01 | 0.155 |
| R-HSA-9022702 | MECP2 regulates transcription of neuronal ligands | 6.995757e-01 | 0.155 |
| R-HSA-5689877 | Josephin domain DUBs | 6.995757e-01 | 0.155 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 7.037750e-01 | 0.153 |
| R-HSA-5654736 | Signaling by FGFR1 | 7.043295e-01 | 0.152 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 7.043295e-01 | 0.152 |
| R-HSA-69236 | G1 Phase | 7.074689e-01 | 0.150 |
| R-HSA-69231 | Cyclin D associated events in G1 | 7.074689e-01 | 0.150 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 7.087913e-01 | 0.149 |
| R-HSA-2022870 | CS-GAG biosynthesis | 7.122655e-01 | 0.147 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 7.122655e-01 | 0.147 |
| R-HSA-9694614 | Attachment and Entry | 7.122655e-01 | 0.147 |
| R-HSA-977225 | Amyloid fiber formation | 7.145663e-01 | 0.146 |
| R-HSA-8964539 | Glutamate and glutamine metabolism | 7.147027e-01 | 0.146 |
| R-HSA-112399 | IRS-mediated signalling | 7.168716e-01 | 0.145 |
| R-HSA-1483166 | Synthesis of PA | 7.168716e-01 | 0.145 |
| R-HSA-5654741 | Signaling by FGFR3 | 7.212239e-01 | 0.142 |
| R-HSA-177135 | Conjugation of benzoate with glycine | 7.261307e-01 | 0.139 |
| R-HSA-192814 | vRNA Synthesis | 7.261307e-01 | 0.139 |
| R-HSA-9754560 | SARS-CoV-2 modulates autophagy | 7.261307e-01 | 0.139 |
| R-HSA-9832991 | Formation of the posterior neural plate | 7.261307e-01 | 0.139 |
| R-HSA-425381 | Bicarbonate transporters | 7.261307e-01 | 0.139 |
| R-HSA-6807047 | Cholesterol biosynthesis via desmosterol | 7.261307e-01 | 0.139 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 7.261307e-01 | 0.139 |
| R-HSA-196819 | Vitamin B1 (thiamin) metabolism | 7.261307e-01 | 0.139 |
| R-HSA-210990 | PECAM1 interactions | 7.261307e-01 | 0.139 |
| R-HSA-391908 | Prostanoid ligand receptors | 7.261307e-01 | 0.139 |
| R-HSA-983712 | Ion channel transport | 7.272068e-01 | 0.138 |
| R-HSA-6809371 | Formation of the cornified envelope | 7.282600e-01 | 0.138 |
| R-HSA-1971475 | Glycosaminoglycan-protein linkage region biosynthesis | 7.300423e-01 | 0.137 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 7.300423e-01 | 0.137 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 7.300423e-01 | 0.137 |
| R-HSA-76071 | RNA Polymerase III Transcription Initiation From Type 3 Promoter | 7.307686e-01 | 0.136 |
| R-HSA-6803529 | FGFR2 alternative splicing | 7.307686e-01 | 0.136 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 7.307686e-01 | 0.136 |
| R-HSA-9694676 | Translation of Replicase and Assembly of the Replication Transcription Complex | 7.307686e-01 | 0.136 |
| R-HSA-3000178 | ECM proteoglycans | 7.371900e-01 | 0.132 |
| R-HSA-917977 | Transferrin endocytosis and recycling | 7.447255e-01 | 0.128 |
| R-HSA-499943 | Interconversion of nucleotide di- and triphosphates | 7.478224e-01 | 0.126 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 7.482504e-01 | 0.126 |
| R-HSA-200425 | Carnitine shuttle | 7.482504e-01 | 0.126 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 7.482504e-01 | 0.126 |
| R-HSA-74182 | Ketone body metabolism | 7.482504e-01 | 0.126 |
| R-HSA-5358493 | Synthesis of diphthamide-EEF2 | 7.503399e-01 | 0.125 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 7.503399e-01 | 0.125 |
| R-HSA-180689 | APOBEC3G mediated resistance to HIV-1 infection | 7.503399e-01 | 0.125 |
| R-HSA-1234158 | Regulation of gene expression by Hypoxia-inducible Factor | 7.503399e-01 | 0.125 |
| R-HSA-9623433 | NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis | 7.503399e-01 | 0.125 |
| R-HSA-425561 | Sodium/Calcium exchangers | 7.503399e-01 | 0.125 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 7.522052e-01 | 0.124 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 7.522052e-01 | 0.124 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 7.522052e-01 | 0.124 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 7.522052e-01 | 0.124 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 7.522052e-01 | 0.124 |
| R-HSA-379724 | tRNA Aminoacylation | 7.522052e-01 | 0.124 |
| R-HSA-9682385 | FLT3 signaling in disease | 7.587642e-01 | 0.120 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 7.587642e-01 | 0.120 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 7.632241e-01 | 0.117 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 7.644931e-01 | 0.117 |
| R-HSA-211999 | CYP2E1 reactions | 7.647469e-01 | 0.116 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 7.647469e-01 | 0.116 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 7.647469e-01 | 0.116 |
| R-HSA-1226099 | Signaling by FGFR in disease | 7.681444e-01 | 0.115 |
| R-HSA-73893 | DNA Damage Bypass | 7.714348e-01 | 0.113 |
| R-HSA-389661 | Glyoxylate metabolism and glycine degradation | 7.714348e-01 | 0.113 |
| R-HSA-597592 | Post-translational protein modification | 7.718535e-01 | 0.112 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 7.721715e-01 | 0.112 |
| R-HSA-196757 | Metabolism of folate and pterines | 7.721715e-01 | 0.112 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 7.724104e-01 | 0.112 |
| R-HSA-2691232 | Constitutive Signaling by NOTCH1 HD Domain Mutants | 7.724104e-01 | 0.112 |
| R-HSA-2691230 | Signaling by NOTCH1 HD Domain Mutants in Cancer | 7.724104e-01 | 0.112 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 7.724104e-01 | 0.112 |
| R-HSA-3656237 | Defective EXT2 causes exostoses 2 | 7.724104e-01 | 0.112 |
| R-HSA-3656253 | Defective EXT1 causes exostoses 1, TRPS2 and CHDS | 7.724104e-01 | 0.112 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 7.724104e-01 | 0.112 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 7.724104e-01 | 0.112 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 7.724104e-01 | 0.112 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 7.724104e-01 | 0.112 |
| R-HSA-69091 | Polymerase switching | 7.724104e-01 | 0.112 |
| R-HSA-69109 | Leading Strand Synthesis | 7.724104e-01 | 0.112 |
| R-HSA-77305 | Beta oxidation of palmitoyl-CoA to myristoyl-CoA | 7.724104e-01 | 0.112 |
| R-HSA-77285 | Beta oxidation of myristoyl-CoA to lauroyl-CoA | 7.724104e-01 | 0.112 |
| R-HSA-9865114 | Maple Syrup Urine Disease | 7.724104e-01 | 0.112 |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 | 7.724104e-01 | 0.112 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 7.724104e-01 | 0.112 |
| R-HSA-177128 | Conjugation of salicylate with glycine | 7.724104e-01 | 0.112 |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation | 7.724104e-01 | 0.112 |
| R-HSA-70688 | Proline catabolism | 7.724104e-01 | 0.112 |
| R-HSA-9842663 | Signaling by LTK | 7.724104e-01 | 0.112 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 7.724104e-01 | 0.112 |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft | 7.724104e-01 | 0.112 |
| R-HSA-1247673 | Erythrocytes take up oxygen and release carbon dioxide | 7.724104e-01 | 0.112 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 7.738686e-01 | 0.111 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 7.738686e-01 | 0.111 |
| R-HSA-2672351 | Stimuli-sensing channels | 7.774346e-01 | 0.109 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 7.802957e-01 | 0.108 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 7.841428e-01 | 0.106 |
| R-HSA-422356 | Regulation of insulin secretion | 7.877246e-01 | 0.104 |
| R-HSA-8963901 | Chylomicron remodeling | 7.925310e-01 | 0.101 |
| R-HSA-9853506 | OGDH complex synthesizes succinyl-CoA from 2-OG | 7.925310e-01 | 0.101 |
| R-HSA-9861559 | PDH complex synthesizes acetyl-CoA from PYR | 7.925310e-01 | 0.101 |
| R-HSA-190373 | FGFR1c ligand binding and activation | 7.925310e-01 | 0.101 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 7.925310e-01 | 0.101 |
| R-HSA-8949664 | Processing of SMDT1 | 7.925310e-01 | 0.101 |
| R-HSA-8877330 | RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) | 7.925310e-01 | 0.101 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 7.925310e-01 | 0.101 |
| R-HSA-9683610 | Maturation of nucleoprotein | 7.925310e-01 | 0.101 |
| R-HSA-2428924 | IGF1R signaling cascade | 7.940514e-01 | 0.100 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 7.949352e-01 | 0.100 |
| R-HSA-5689901 | Metalloprotease DUBs | 7.949352e-01 | 0.100 |
| R-HSA-9609507 | Protein localization | 7.955547e-01 | 0.099 |
| R-HSA-9843745 | Adipogenesis | 7.969505e-01 | 0.099 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 7.971528e-01 | 0.098 |
| R-HSA-201556 | Signaling by ALK | 7.971528e-01 | 0.098 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 7.971528e-01 | 0.098 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 8.036001e-01 | 0.095 |
| R-HSA-171306 | Packaging Of Telomere Ends | 8.087048e-01 | 0.092 |
| R-HSA-264876 | Insulin processing | 8.087048e-01 | 0.092 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 8.087596e-01 | 0.092 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 8.087596e-01 | 0.092 |
| R-HSA-167169 | HIV Transcription Elongation | 8.087596e-01 | 0.092 |
| R-HSA-1170546 | Prolactin receptor signaling | 8.108739e-01 | 0.091 |
| R-HSA-9859138 | BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV | 8.108739e-01 | 0.091 |
| R-HSA-418457 | cGMP effects | 8.108739e-01 | 0.091 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 8.108739e-01 | 0.091 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 8.108739e-01 | 0.091 |
| R-HSA-1483115 | Hydrolysis of LPC | 8.108739e-01 | 0.091 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 8.108739e-01 | 0.091 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 8.108739e-01 | 0.091 |
| R-HSA-77350 | Beta oxidation of hexanoyl-CoA to butanoyl-CoA | 8.108739e-01 | 0.091 |
| R-HSA-77310 | Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA | 8.108739e-01 | 0.091 |
| R-HSA-77348 | Beta oxidation of octanoyl-CoA to hexanoyl-CoA | 8.108739e-01 | 0.091 |
| R-HSA-9828642 | Respiratory syncytial virus genome transcription | 8.108739e-01 | 0.091 |
| R-HSA-435354 | Zinc transporters | 8.108739e-01 | 0.091 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 8.198003e-01 | 0.086 |
| R-HSA-9610379 | HCMV Late Events | 8.200680e-01 | 0.086 |
| R-HSA-5654738 | Signaling by FGFR2 | 8.217509e-01 | 0.085 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 8.275960e-01 | 0.082 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 8.275960e-01 | 0.082 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 8.275960e-01 | 0.082 |
| R-HSA-73780 | RNA Polymerase III Chain Elongation | 8.275960e-01 | 0.082 |
| R-HSA-110312 | Translesion synthesis by REV1 | 8.275960e-01 | 0.082 |
| R-HSA-9857492 | Protein lipoylation | 8.275960e-01 | 0.082 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling | 8.275960e-01 | 0.082 |
| R-HSA-167172 | Transcription of the HIV genome | 8.301485e-01 | 0.081 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 8.301485e-01 | 0.081 |
| R-HSA-6811438 | Intra-Golgi traffic | 8.302934e-01 | 0.081 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 8.337912e-01 | 0.079 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 8.337912e-01 | 0.079 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 8.402573e-01 | 0.076 |
| R-HSA-73928 | Depyrimidination | 8.402573e-01 | 0.076 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 8.418581e-01 | 0.075 |
| R-HSA-5656121 | Translesion synthesis by POLI | 8.428405e-01 | 0.074 |
| R-HSA-168275 | Entry of Influenza Virion into Host Cell via Endocytosis | 8.428405e-01 | 0.074 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 8.428405e-01 | 0.074 |
| R-HSA-2485179 | Activation of the phototransduction cascade | 8.428405e-01 | 0.074 |
| R-HSA-70350 | Fructose catabolism | 8.428405e-01 | 0.074 |
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand | 8.428405e-01 | 0.074 |
| R-HSA-5635838 | Activation of SMO | 8.428405e-01 | 0.074 |
| R-HSA-9678110 | Attachment and Entry | 8.428405e-01 | 0.074 |
| R-HSA-9706369 | Negative regulation of FLT3 | 8.428405e-01 | 0.074 |
| R-HSA-168268 | Virus Assembly and Release | 8.428405e-01 | 0.074 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 8.446108e-01 | 0.073 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 8.451859e-01 | 0.073 |
| R-HSA-8951664 | Neddylation | 8.472509e-01 | 0.072 |
| R-HSA-9007101 | Rab regulation of trafficking | 8.533092e-01 | 0.069 |
| R-HSA-2129379 | Molecules associated with elastic fibres | 8.558662e-01 | 0.068 |
| R-HSA-8963693 | Aspartate and asparagine metabolism | 8.558662e-01 | 0.068 |
| R-HSA-1474244 | Extracellular matrix organization | 8.558711e-01 | 0.068 |
| R-HSA-5655862 | Translesion synthesis by POLK | 8.567379e-01 | 0.067 |
| R-HSA-9027307 | Biosynthesis of maresin-like SPMs | 8.567379e-01 | 0.067 |
| R-HSA-9690406 | Transcriptional regulation of testis differentiation | 8.567379e-01 | 0.067 |
| R-HSA-77288 | mitochondrial fatty acid beta-oxidation of unsaturated fatty acids | 8.567379e-01 | 0.067 |
| R-HSA-964975 | Vitamin B6 activation to pyridoxal phosphate | 8.567379e-01 | 0.067 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 8.567379e-01 | 0.067 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 8.567379e-01 | 0.067 |
| R-HSA-432047 | Passive transport by Aquaporins | 8.567379e-01 | 0.067 |
| R-HSA-77346 | Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA | 8.567379e-01 | 0.067 |
| R-HSA-5661270 | Formation of xylulose-5-phosphate | 8.567379e-01 | 0.067 |
| R-HSA-400511 | Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polyp... | 8.567379e-01 | 0.067 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 8.638840e-01 | 0.064 |
| R-HSA-9937080 | Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 8.658690e-01 | 0.063 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 8.658690e-01 | 0.063 |
| R-HSA-1538133 | G0 and Early G1 | 8.658690e-01 | 0.063 |
| R-HSA-8979227 | Triglyceride metabolism | 8.659296e-01 | 0.063 |
| R-HSA-9033241 | Peroxisomal protein import | 8.659296e-01 | 0.063 |
| R-HSA-774815 | Nucleosome assembly | 8.671641e-01 | 0.062 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 8.671641e-01 | 0.062 |
| R-HSA-3560782 | Diseases associated with glycosaminoglycan metabolism | 8.671641e-01 | 0.062 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 8.694071e-01 | 0.061 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 8.694071e-01 | 0.061 |
| R-HSA-139853 | Elevation of cytosolic Ca2+ levels | 8.694071e-01 | 0.061 |
| R-HSA-4641263 | Regulation of FZD by ubiquitination | 8.694071e-01 | 0.061 |
| R-HSA-2408550 | Metabolism of ingested H2SeO4 and H2SeO3 into H2Se | 8.694071e-01 | 0.061 |
| R-HSA-6798163 | Choline catabolism | 8.694071e-01 | 0.061 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 8.713212e-01 | 0.060 |
| R-HSA-977443 | GABA receptor activation | 8.732229e-01 | 0.059 |
| R-HSA-1222556 | ROS and RNS production in phagocytes | 8.744666e-01 | 0.058 |
| R-HSA-159418 | Recycling of bile acids and salts | 8.752308e-01 | 0.058 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 8.752308e-01 | 0.058 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 8.752308e-01 | 0.058 |
| R-HSA-5609975 | Diseases associated with glycosylation precursor biosynthesis | 8.752308e-01 | 0.058 |
| R-HSA-190236 | Signaling by FGFR | 8.756023e-01 | 0.058 |
| R-HSA-71403 | Citric acid cycle (TCA cycle) | 8.808090e-01 | 0.055 |
| R-HSA-5358508 | Mismatch Repair | 8.809566e-01 | 0.055 |
| R-HSA-190242 | FGFR1 ligand binding and activation | 8.809566e-01 | 0.055 |
| R-HSA-2142700 | Biosynthesis of Lipoxins (LX) | 8.809566e-01 | 0.055 |
| R-HSA-196791 | Vitamin D (calciferol) metabolism | 8.809566e-01 | 0.055 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 8.828045e-01 | 0.054 |
| R-HSA-2024101 | CS/DS degradation | 8.839865e-01 | 0.054 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 8.839865e-01 | 0.054 |
| R-HSA-1483249 | Inositol phosphate metabolism | 8.853657e-01 | 0.053 |
| R-HSA-186797 | Signaling by PDGF | 8.867860e-01 | 0.052 |
| R-HSA-1980143 | Signaling by NOTCH1 | 8.868756e-01 | 0.052 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 8.914853e-01 | 0.050 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 8.914853e-01 | 0.050 |
| R-HSA-9913635 | Strand-asynchronous mitochondrial DNA replication | 8.914853e-01 | 0.050 |
| R-HSA-9834899 | Specification of the neural plate border | 8.914853e-01 | 0.050 |
| R-HSA-156587 | Amino Acid conjugation | 8.914853e-01 | 0.050 |
| R-HSA-159424 | Conjugation of carboxylic acids | 8.914853e-01 | 0.050 |
| R-HSA-844456 | The NLRP3 inflammasome | 8.914853e-01 | 0.050 |
| R-HSA-1480926 | O2/CO2 exchange in erythrocytes | 8.914853e-01 | 0.050 |
| R-HSA-912631 | Regulation of signaling by CBL | 8.914853e-01 | 0.050 |
| R-HSA-1237112 | Methionine salvage pathway | 8.914853e-01 | 0.050 |
| R-HSA-1237044 | Erythrocytes take up carbon dioxide and release oxygen | 8.914853e-01 | 0.050 |
| R-HSA-8964058 | HDL remodeling | 8.914853e-01 | 0.050 |
| R-HSA-9694631 | Maturation of nucleoprotein | 8.914853e-01 | 0.050 |
| R-HSA-5686938 | Regulation of TLR by endogenous ligand | 8.921703e-01 | 0.050 |
| R-HSA-9694635 | Translation of Structural Proteins | 8.926753e-01 | 0.049 |
| R-HSA-216083 | Integrin cell surface interactions | 8.982165e-01 | 0.047 |
| R-HSA-381042 | PERK regulates gene expression | 8.998146e-01 | 0.046 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.002652e-01 | 0.046 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.002652e-01 | 0.046 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 9.010833e-01 | 0.045 |
| R-HSA-9609523 | Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 9.010833e-01 | 0.045 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 9.010833e-01 | 0.045 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 9.010833e-01 | 0.045 |
| R-HSA-1482922 | Acyl chain remodelling of PI | 9.010833e-01 | 0.045 |
| R-HSA-196108 | Pregnenolone biosynthesis | 9.010833e-01 | 0.045 |
| R-HSA-3322077 | Glycogen synthesis | 9.010833e-01 | 0.045 |
| R-HSA-9659379 | Sensory processing of sound | 9.035078e-01 | 0.044 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.069555e-01 | 0.042 |
| R-HSA-69186 | Lagging Strand Synthesis | 9.098330e-01 | 0.041 |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane | 9.098330e-01 | 0.041 |
| R-HSA-1482925 | Acyl chain remodelling of PG | 9.098330e-01 | 0.041 |
| R-HSA-9636383 | Prevention of phagosomal-lysosomal fusion | 9.098330e-01 | 0.041 |
| R-HSA-140837 | Intrinsic Pathway of Fibrin Clot Formation | 9.098330e-01 | 0.041 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 9.133205e-01 | 0.039 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 9.136092e-01 | 0.039 |
| R-HSA-71064 | Lysine catabolism | 9.136092e-01 | 0.039 |
| R-HSA-110331 | Cleavage of the damaged purine | 9.136092e-01 | 0.039 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 9.136652e-01 | 0.039 |
| R-HSA-9830369 | Kidney development | 9.152809e-01 | 0.038 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 9.178091e-01 | 0.037 |
| R-HSA-211958 | Miscellaneous substrates | 9.178091e-01 | 0.037 |
| R-HSA-977347 | Serine metabolism | 9.178091e-01 | 0.037 |
| R-HSA-193048 | Androgen biosynthesis | 9.178091e-01 | 0.037 |
| R-HSA-1566948 | Elastic fibre formation | 9.198182e-01 | 0.036 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 9.198182e-01 | 0.036 |
| R-HSA-73927 | Depurination | 9.198182e-01 | 0.036 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 9.198182e-01 | 0.036 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 9.198182e-01 | 0.036 |
| R-HSA-5619102 | SLC transporter disorders | 9.202466e-01 | 0.036 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 9.250801e-01 | 0.034 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 9.250801e-01 | 0.034 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 9.250801e-01 | 0.034 |
| R-HSA-71384 | Ethanol oxidation | 9.250801e-01 | 0.034 |
| R-HSA-6807062 | Cholesterol biosynthesis via lathosterol | 9.250801e-01 | 0.034 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 9.253822e-01 | 0.034 |
| R-HSA-71336 | Pentose phosphate pathway | 9.256053e-01 | 0.034 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 9.296645e-01 | 0.032 |
| R-HSA-73886 | Chromosome Maintenance | 9.303927e-01 | 0.031 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 9.309964e-01 | 0.031 |
| R-HSA-71240 | Tryptophan catabolism | 9.309964e-01 | 0.031 |
| R-HSA-9018682 | Biosynthesis of maresins | 9.317083e-01 | 0.031 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 9.317083e-01 | 0.031 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 9.317083e-01 | 0.031 |
| R-HSA-1369062 | ABC transporters in lipid homeostasis | 9.317083e-01 | 0.031 |
| R-HSA-9830674 | Formation of the ureteric bud | 9.317083e-01 | 0.031 |
| R-HSA-446210 | Synthesis of UDP-N-acetyl-glucosamine | 9.317083e-01 | 0.031 |
| R-HSA-1855167 | Synthesis of pyrophosphates in the cytosol | 9.317083e-01 | 0.031 |
| R-HSA-157579 | Telomere Maintenance | 9.330373e-01 | 0.030 |
| R-HSA-8978934 | Metabolism of cofactors | 9.332701e-01 | 0.030 |
| R-HSA-9865881 | Complex III assembly | 9.377505e-01 | 0.028 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 9.378479e-01 | 0.028 |
| R-HSA-167161 | HIV Transcription Initiation | 9.406887e-01 | 0.027 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 9.406887e-01 | 0.027 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 9.406887e-01 | 0.027 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 9.406887e-01 | 0.027 |
| R-HSA-6782135 | Dual incision in TC-NER | 9.428156e-01 | 0.026 |
| R-HSA-416476 | G alpha (q) signalling events | 9.428440e-01 | 0.026 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 9.432584e-01 | 0.025 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 9.432584e-01 | 0.025 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 9.432584e-01 | 0.025 |
| R-HSA-1482801 | Acyl chain remodelling of PS | 9.432584e-01 | 0.025 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 9.432584e-01 | 0.025 |
| R-HSA-70221 | Glycogen breakdown (glycogenolysis) | 9.432584e-01 | 0.025 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 9.450355e-01 | 0.025 |
| R-HSA-186712 | Regulation of beta-cell development | 9.465405e-01 | 0.024 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 9.477271e-01 | 0.023 |
| R-HSA-2122948 | Activated NOTCH1 Transmits Signal to the Nucleus | 9.482792e-01 | 0.023 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 9.482792e-01 | 0.023 |
| R-HSA-9638630 | Attachment of bacteria to epithelial cells | 9.482792e-01 | 0.023 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 9.490778e-01 | 0.023 |
| R-HSA-8854214 | TBC/RABGAPs | 9.490778e-01 | 0.023 |
| R-HSA-5683826 | Surfactant metabolism | 9.528354e-01 | 0.021 |
| R-HSA-156581 | Methylation | 9.528354e-01 | 0.021 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 9.528561e-01 | 0.021 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 9.528561e-01 | 0.021 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 9.528561e-01 | 0.021 |
| R-HSA-901032 | ER Quality Control Compartment (ERQC) | 9.528561e-01 | 0.021 |
| R-HSA-193807 | Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 9.528561e-01 | 0.021 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 9.529438e-01 | 0.021 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 9.563270e-01 | 0.019 |
| R-HSA-1614558 | Degradation of cysteine and homocysteine | 9.563270e-01 | 0.019 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 9.570281e-01 | 0.019 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 9.570281e-01 | 0.019 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 9.570281e-01 | 0.019 |
| R-HSA-622312 | Inflammasomes | 9.570281e-01 | 0.019 |
| R-HSA-1989781 | PPARA activates gene expression | 9.574356e-01 | 0.019 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 9.584208e-01 | 0.018 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 9.595704e-01 | 0.018 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 9.595704e-01 | 0.018 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 9.595704e-01 | 0.018 |
| R-HSA-72086 | mRNA Capping | 9.608312e-01 | 0.017 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 9.608312e-01 | 0.017 |
| R-HSA-1592389 | Activation of Matrix Metalloproteinases | 9.608312e-01 | 0.017 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 9.608312e-01 | 0.017 |
| R-HSA-72306 | tRNA processing | 9.616363e-01 | 0.017 |
| R-HSA-211981 | Xenobiotics | 9.620025e-01 | 0.017 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 9.642980e-01 | 0.016 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 9.642980e-01 | 0.016 |
| R-HSA-112311 | Neurotransmitter clearance | 9.642980e-01 | 0.016 |
| R-HSA-8963899 | Plasma lipoprotein remodeling | 9.653774e-01 | 0.015 |
| R-HSA-425410 | Metal ion SLC transporters | 9.653774e-01 | 0.015 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 9.656376e-01 | 0.015 |
| R-HSA-162710 | Synthesis of glycosylphosphatidylinositol (GPI) | 9.674580e-01 | 0.014 |
| R-HSA-1296071 | Potassium Channels | 9.690712e-01 | 0.014 |
| R-HSA-2024096 | HS-GAG degradation | 9.703386e-01 | 0.013 |
| R-HSA-4791275 | Signaling by WNT in cancer | 9.703386e-01 | 0.013 |
| R-HSA-9748787 | Azathioprine ADME | 9.703776e-01 | 0.013 |
| R-HSA-2514856 | The phototransduction cascade | 9.726090e-01 | 0.012 |
| R-HSA-5083635 | Defective B3GALTL causes PpS | 9.729643e-01 | 0.012 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 9.729643e-01 | 0.012 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 9.729643e-01 | 0.012 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 9.750080e-01 | 0.011 |
| R-HSA-1482788 | Acyl chain remodelling of PC | 9.753577e-01 | 0.011 |
| R-HSA-5223345 | Miscellaneous transport and binding events | 9.753577e-01 | 0.011 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 9.753577e-01 | 0.011 |
| R-HSA-975634 | Retinoid metabolism and transport | 9.767146e-01 | 0.010 |
| R-HSA-203615 | eNOS activation | 9.775394e-01 | 0.010 |
| R-HSA-1483255 | PI Metabolism | 9.785059e-01 | 0.009 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 9.795280e-01 | 0.009 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 9.795280e-01 | 0.009 |
| R-HSA-1482839 | Acyl chain remodelling of PE | 9.795280e-01 | 0.009 |
| R-HSA-9749641 | Aspirin ADME | 9.798008e-01 | 0.009 |
| R-HSA-1793185 | Chondroitin sulfate/dermatan sulfate metabolism | 9.800167e-01 | 0.009 |
| R-HSA-9753281 | Paracetamol ADME | 9.800167e-01 | 0.009 |
| R-HSA-418555 | G alpha (s) signalling events | 9.811348e-01 | 0.008 |
| R-HSA-2022928 | HS-GAG biosynthesis | 9.813407e-01 | 0.008 |
| R-HSA-9845576 | Glycosphingolipid transport | 9.813407e-01 | 0.008 |
| R-HSA-917937 | Iron uptake and transport | 9.824943e-01 | 0.008 |
| R-HSA-5621480 | Dectin-2 family | 9.829512e-01 | 0.007 |
| R-HSA-5173214 | O-glycosylation of TSR domain-containing proteins | 9.829929e-01 | 0.007 |
| R-HSA-2142789 | Ubiquinol biosynthesis | 9.829929e-01 | 0.007 |
| R-HSA-9931953 | Biofilm formation | 9.844990e-01 | 0.007 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 9.854652e-01 | 0.006 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 9.854652e-01 | 0.006 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 9.858718e-01 | 0.006 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 9.858718e-01 | 0.006 |
| R-HSA-3781860 | Diseases associated with N-glycosylation of proteins | 9.858718e-01 | 0.006 |
| R-HSA-1474290 | Collagen formation | 9.865492e-01 | 0.006 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 9.865830e-01 | 0.006 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 9.865830e-01 | 0.006 |
| R-HSA-9854311 | Maturation of TCA enzymes and regulation of TCA cycle | 9.871230e-01 | 0.006 |
| R-HSA-8982491 | Glycogen metabolism | 9.871230e-01 | 0.006 |
| R-HSA-211976 | Endogenous sterols | 9.876170e-01 | 0.005 |
| R-HSA-73817 | Purine ribonucleoside monophosphate biosynthesis | 9.882635e-01 | 0.005 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 9.886645e-01 | 0.005 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 9.893031e-01 | 0.005 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 9.893031e-01 | 0.005 |
| R-HSA-6799198 | Complex I biogenesis | 9.894571e-01 | 0.005 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 9.897673e-01 | 0.004 |
| R-HSA-75876 | Synthesis of very long-chain fatty acyl-CoAs | 9.911143e-01 | 0.004 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 9.917042e-01 | 0.004 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 9.917270e-01 | 0.004 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 9.919015e-01 | 0.004 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 9.921855e-01 | 0.003 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 9.923716e-01 | 0.003 |
| R-HSA-196807 | Nicotinate metabolism | 9.923716e-01 | 0.003 |
| R-HSA-196071 | Metabolism of steroid hormones | 9.923716e-01 | 0.003 |
| R-HSA-77286 | mitochondrial fatty acid beta-oxidation of saturated fatty acids | 9.926190e-01 | 0.003 |
| R-HSA-1614635 | Sulfur amino acid metabolism | 9.927125e-01 | 0.003 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 9.929669e-01 | 0.003 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 9.932730e-01 | 0.003 |
| R-HSA-6805567 | Keratinization | 9.936608e-01 | 0.003 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 9.944929e-01 | 0.002 |
| R-HSA-373080 | Class B/2 (Secretin family receptors) | 9.945913e-01 | 0.002 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 9.953588e-01 | 0.002 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 9.957701e-01 | 0.002 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.961195e-01 | 0.002 |
| R-HSA-8956320 | Nucleotide biosynthesis | 9.964867e-01 | 0.002 |
| R-HSA-6783783 | Interleukin-10 signaling | 9.969015e-01 | 0.001 |
| R-HSA-9955298 | SLC-mediated transport of organic anions | 9.969015e-01 | 0.001 |
| R-HSA-191273 | Cholesterol biosynthesis | 9.969015e-01 | 0.001 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 9.970439e-01 | 0.001 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 9.971472e-01 | 0.001 |
| R-HSA-418594 | G alpha (i) signalling events | 9.972039e-01 | 0.001 |
| R-HSA-8935690 | Digestion | 9.973407e-01 | 0.001 |
| R-HSA-611105 | Respiratory electron transport | 9.975907e-01 | 0.001 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.976490e-01 | 0.001 |
| R-HSA-2980736 | Peptide hormone metabolism | 9.979600e-01 | 0.001 |
| R-HSA-1638091 | Heparan sulfate/heparin (HS-GAG) metabolism | 9.979872e-01 | 0.001 |
| R-HSA-180786 | Extension of Telomeres | 9.979872e-01 | 0.001 |
| R-HSA-4085001 | Sialic acid metabolism | 9.979872e-01 | 0.001 |
| R-HSA-156590 | Glutathione conjugation | 9.981657e-01 | 0.001 |
| R-HSA-3781865 | Diseases of glycosylation | 9.983256e-01 | 0.001 |
| R-HSA-1442490 | Collagen degradation | 9.983284e-01 | 0.001 |
| R-HSA-163125 | Post-translational modification: synthesis of GPI-anchored proteins | 9.985185e-01 | 0.001 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.985849e-01 | 0.001 |
| R-HSA-8963743 | Digestion and absorption | 9.986117e-01 | 0.001 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 9.987349e-01 | 0.001 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 9.988296e-01 | 0.001 |
| R-HSA-112310 | Neurotransmitter release cycle | 9.989501e-01 | 0.000 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 9.990426e-01 | 0.000 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 9.992755e-01 | 0.000 |
| R-HSA-2187338 | Visual phototransduction | 9.993249e-01 | 0.000 |
| R-HSA-8957322 | Metabolism of steroids | 9.993368e-01 | 0.000 |
| R-HSA-1483257 | Phospholipid metabolism | 9.993826e-01 | 0.000 |
| R-HSA-74259 | Purine catabolism | 9.993983e-01 | 0.000 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 9.994517e-01 | 0.000 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.994542e-01 | 0.000 |
| R-HSA-5389840 | Mitochondrial translation elongation | 9.994647e-01 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 9.994968e-01 | 0.000 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 9.997044e-01 | 0.000 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 9.997394e-01 | 0.000 |
| R-HSA-420499 | Class C/3 (Metabotropic glutamate/pheromone receptors) | 9.998762e-01 | 0.000 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.998822e-01 | 0.000 |
| R-HSA-388396 | GPCR downstream signalling | 9.998980e-01 | 0.000 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.999053e-01 | 0.000 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 9.999182e-01 | 0.000 |
| R-HSA-2029481 | FCGR activation | 9.999291e-01 | 0.000 |
| R-HSA-5368287 | Mitochondrial translation | 9.999332e-01 | 0.000 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 9.999412e-01 | 0.000 |
| R-HSA-15869 | Metabolism of nucleotides | 9.999453e-01 | 0.000 |
| R-HSA-2168880 | Scavenging of heme from plasma | 9.999464e-01 | 0.000 |
| R-HSA-5368286 | Mitochondrial translation initiation | 9.999595e-01 | 0.000 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 9.999653e-01 | 0.000 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.999699e-01 | 0.000 |
| R-HSA-9717189 | Sensory perception of taste | 9.999827e-01 | 0.000 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 9.999827e-01 | 0.000 |
| R-HSA-5419276 | Mitochondrial translation termination | 9.999867e-01 | 0.000 |
| R-HSA-6803157 | Antimicrobial peptides | 9.999890e-01 | 0.000 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 9.999939e-01 | 0.000 |
| R-HSA-372790 | Signaling by GPCR | 9.999947e-01 | 0.000 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 9.999949e-01 | 0.000 |
| R-HSA-9717207 | Sensory perception of sweet, bitter, and umami (glutamate) taste | 9.999970e-01 | 0.000 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 9.999970e-01 | 0.000 |
| R-HSA-9748784 | Drug ADME | 9.999971e-01 | 0.000 |
| R-HSA-977606 | Regulation of Complement cascade | 9.999975e-01 | 0.000 |
| R-HSA-2142753 | Arachidonate metabolism | 9.999977e-01 | 0.000 |
| R-HSA-8956319 | Nucleotide catabolism | 9.999984e-01 | 0.000 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.999985e-01 | 0.000 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.999993e-01 | 0.000 |
| R-HSA-5173105 | O-linked glycosylation | 9.999994e-01 | 0.000 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 9.999994e-01 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 9.999995e-01 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.999996e-01 | 0.000 |
| R-HSA-428157 | Sphingolipid metabolism | 9.999997e-01 | 0.000 |
| R-HSA-166658 | Complement cascade | 9.999997e-01 | 0.000 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 9.999999e-01 | 0.000 |
| R-HSA-375276 | Peptide ligand-binding receptors | 1.000000e+00 | 0.000 |
| R-HSA-9640148 | Infection with Enterobacteria | 1.000000e+00 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 1.000000e+00 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 1.000000e+00 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-211859 | Biological oxidations | 1.000000e+00 | 0.000 |
| R-HSA-9752946 | Expression and translocation of olfactory receptors | 1.000000e+00 | -0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | -0.000 |
| R-HSA-381753 | Olfactory Signaling Pathway | 1.000000e+00 | -0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | -0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | -0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
GAK |
0.915 | 0.643 | 1 | 0.919 |
BIKE |
0.904 | 0.659 | 1 | 0.957 |
AAK1 |
0.901 | 0.695 | 1 | 0.923 |
PBK |
0.894 | 0.605 | 1 | 0.937 |
PKR |
0.888 | 0.080 | 1 | 0.742 |
VRK2 |
0.887 | -0.039 | 1 | 0.763 |
MPSK1 |
0.887 | 0.447 | 1 | 0.849 |
NEK1 |
0.883 | 0.026 | 1 | 0.724 |
TNIK |
0.883 | 0.033 | 3 | 0.872 |
TAK1 |
0.883 | -0.106 | 1 | 0.693 |
VRK1 |
0.882 | -0.120 | 2 | 0.881 |
MINK |
0.881 | -0.024 | 1 | 0.679 |
GCK |
0.880 | -0.019 | 1 | 0.669 |
NEK5 |
0.880 | 0.083 | 1 | 0.754 |
LRRK2 |
0.879 | -0.106 | 2 | 0.896 |
TTK |
0.878 | 0.034 | -2 | 0.856 |
MEKK2 |
0.877 | -0.025 | 2 | 0.852 |
PDK1 |
0.877 | -0.041 | 1 | 0.691 |
EEF2K |
0.877 | -0.034 | 3 | 0.840 |
ASK1 |
0.876 | -0.155 | 1 | 0.647 |
LKB1 |
0.876 | 0.025 | -3 | 0.883 |
NIK |
0.876 | -0.004 | -3 | 0.917 |
BMPR2 |
0.876 | -0.059 | -2 | 0.919 |
KHS1 |
0.876 | -0.008 | 1 | 0.656 |
HGK |
0.875 | -0.029 | 3 | 0.870 |
MEK1 |
0.875 | -0.141 | 2 | 0.883 |
DAPK2 |
0.875 | 0.033 | -3 | 0.906 |
MST2 |
0.875 | -0.069 | 1 | 0.694 |
MAP3K15 |
0.874 | -0.081 | 1 | 0.657 |
MOS |
0.874 | 0.135 | 1 | 0.767 |
BRAF |
0.873 | -0.111 | -4 | 0.867 |
TAO2 |
0.873 | -0.084 | 2 | 0.895 |
MST3 |
0.873 | 0.020 | 2 | 0.888 |
MST1 |
0.873 | -0.110 | 1 | 0.677 |
ALK4 |
0.872 | 0.015 | -2 | 0.877 |
CAMLCK |
0.872 | 0.036 | -2 | 0.880 |
KHS2 |
0.872 | 0.010 | 1 | 0.654 |
TAO3 |
0.872 | -0.018 | 1 | 0.681 |
MYO3B |
0.871 | 0.001 | 2 | 0.870 |
MEK5 |
0.871 | -0.202 | 2 | 0.870 |
MEKK6 |
0.871 | -0.051 | 1 | 0.694 |
HPK1 |
0.871 | -0.043 | 1 | 0.645 |
CAMKK2 |
0.870 | -0.088 | -2 | 0.795 |
NEK4 |
0.870 | -0.051 | 1 | 0.696 |
ANKRD3 |
0.869 | -0.036 | 1 | 0.751 |
CAMKK1 |
0.869 | -0.112 | -2 | 0.798 |
PRPK |
0.869 | -0.041 | -1 | 0.878 |
ALPHAK3 |
0.869 | -0.083 | -1 | 0.793 |
MEKK1 |
0.869 | -0.074 | 1 | 0.713 |
OSR1 |
0.868 | -0.081 | 2 | 0.842 |
PASK |
0.867 | 0.033 | -3 | 0.902 |
YSK1 |
0.867 | -0.060 | 2 | 0.856 |
ALK2 |
0.867 | 0.042 | -2 | 0.856 |
LATS1 |
0.867 | 0.062 | -3 | 0.892 |
DMPK1 |
0.867 | 0.116 | -3 | 0.795 |
CAMK1B |
0.866 | 0.033 | -3 | 0.899 |
MYO3A |
0.866 | -0.082 | 1 | 0.658 |
NEK8 |
0.865 | -0.132 | 2 | 0.869 |
NEK11 |
0.865 | -0.148 | 1 | 0.663 |
CDKL1 |
0.864 | 0.094 | -3 | 0.850 |
DLK |
0.864 | -0.205 | 1 | 0.700 |
TGFBR1 |
0.864 | 0.051 | -2 | 0.849 |
MEKK3 |
0.863 | -0.111 | 1 | 0.690 |
DAPK3 |
0.863 | 0.050 | -3 | 0.841 |
JNK2 |
0.863 | 0.029 | 1 | 0.503 |
YSK4 |
0.863 | -0.097 | 1 | 0.667 |
BMPR1B |
0.863 | 0.093 | 1 | 0.671 |
SKMLCK |
0.862 | 0.125 | -2 | 0.893 |
NLK |
0.862 | 0.021 | 1 | 0.700 |
MEK2 |
0.862 | -0.218 | 2 | 0.851 |
P38A |
0.861 | 0.048 | 1 | 0.615 |
JNK3 |
0.861 | 0.010 | 1 | 0.541 |
PRP4 |
0.861 | 0.062 | -3 | 0.841 |
ROCK2 |
0.861 | 0.073 | -3 | 0.829 |
ATR |
0.860 | -0.050 | 1 | 0.691 |
ICK |
0.860 | 0.070 | -3 | 0.882 |
ZAK |
0.859 | -0.153 | 1 | 0.661 |
STLK3 |
0.859 | -0.239 | 1 | 0.635 |
SMMLCK |
0.858 | -0.014 | -3 | 0.858 |
MLK2 |
0.858 | -0.031 | 2 | 0.865 |
PIM1 |
0.857 | 0.269 | -3 | 0.828 |
P38B |
0.856 | 0.025 | 1 | 0.536 |
ERK5 |
0.856 | 0.116 | 1 | 0.731 |
LOK |
0.856 | -0.077 | -2 | 0.800 |
COT |
0.856 | 0.197 | 2 | 0.919 |
ACVR2B |
0.856 | -0.008 | -2 | 0.845 |
PIM3 |
0.855 | 0.296 | -3 | 0.883 |
PERK |
0.855 | -0.071 | -2 | 0.875 |
RAF1 |
0.854 | -0.090 | 1 | 0.720 |
GRK7 |
0.854 | 0.076 | 1 | 0.667 |
ACVR2A |
0.853 | -0.025 | -2 | 0.833 |
HRI |
0.852 | -0.083 | -2 | 0.886 |
NEK9 |
0.852 | -0.058 | 2 | 0.883 |
MASTL |
0.851 | -0.042 | -2 | 0.852 |
WNK4 |
0.851 | -0.033 | -2 | 0.907 |
MLK1 |
0.851 | -0.060 | 2 | 0.865 |
DAPK1 |
0.850 | 0.025 | -3 | 0.827 |
CAMK2G |
0.850 | -0.040 | 2 | 0.862 |
TLK2 |
0.850 | -0.081 | 1 | 0.657 |
WNK1 |
0.849 | 0.046 | -2 | 0.909 |
PLK1 |
0.849 | -0.077 | -2 | 0.843 |
GRK6 |
0.849 | -0.038 | 1 | 0.707 |
CHAK2 |
0.849 | -0.013 | -1 | 0.850 |
MAK |
0.849 | 0.154 | -2 | 0.756 |
PIM2 |
0.848 | 0.194 | -3 | 0.786 |
BMPR1A |
0.848 | 0.046 | 1 | 0.653 |
PKN3 |
0.848 | 0.022 | -3 | 0.873 |
IRAK4 |
0.848 | -0.020 | 1 | 0.726 |
TAO1 |
0.848 | -0.117 | 1 | 0.621 |
TSSK2 |
0.848 | 0.005 | -5 | 0.883 |
HIPK1 |
0.847 | 0.065 | 1 | 0.609 |
GRK5 |
0.847 | -0.096 | -3 | 0.902 |
DSTYK |
0.847 | 0.063 | 2 | 0.932 |
NEK2 |
0.847 | -0.058 | 2 | 0.861 |
CLK3 |
0.847 | 0.166 | 1 | 0.700 |
BUB1 |
0.846 | 0.091 | -5 | 0.824 |
RIPK3 |
0.846 | 0.003 | 3 | 0.785 |
DCAMKL1 |
0.846 | 0.037 | -3 | 0.822 |
RIPK1 |
0.846 | -0.116 | 1 | 0.711 |
CDKL5 |
0.846 | 0.123 | -3 | 0.840 |
PDHK4 |
0.845 | -0.225 | 1 | 0.726 |
AMPKA1 |
0.845 | 0.030 | -3 | 0.891 |
P38G |
0.845 | 0.004 | 1 | 0.443 |
HASPIN |
0.845 | -0.007 | -1 | 0.717 |
NEK3 |
0.844 | -0.091 | 1 | 0.676 |
TLK1 |
0.844 | -0.137 | -2 | 0.870 |
P38D |
0.843 | 0.035 | 1 | 0.482 |
ROCK1 |
0.843 | 0.031 | -3 | 0.791 |
PKCD |
0.843 | 0.044 | 2 | 0.841 |
CDC7 |
0.843 | 0.012 | 1 | 0.714 |
MST4 |
0.843 | 0.056 | 2 | 0.893 |
CDK5 |
0.842 | 0.053 | 1 | 0.600 |
PDHK1 |
0.841 | -0.216 | 1 | 0.717 |
NUAK2 |
0.841 | 0.061 | -3 | 0.879 |
SLK |
0.840 | -0.127 | -2 | 0.745 |
MLK3 |
0.840 | -0.022 | 2 | 0.802 |
TSSK1 |
0.840 | 0.057 | -3 | 0.907 |
MTOR |
0.840 | -0.008 | 1 | 0.668 |
PKN2 |
0.840 | 0.004 | -3 | 0.878 |
CHK1 |
0.839 | 0.005 | -3 | 0.853 |
CRIK |
0.839 | 0.059 | -3 | 0.746 |
PINK1 |
0.839 | -0.034 | 1 | 0.756 |
ERK2 |
0.839 | -0.053 | 1 | 0.557 |
DYRK2 |
0.839 | 0.033 | 1 | 0.576 |
P70S6KB |
0.839 | 0.038 | -3 | 0.835 |
SGK3 |
0.838 | 0.069 | -3 | 0.807 |
MLK4 |
0.838 | -0.075 | 2 | 0.777 |
ERK1 |
0.838 | 0.007 | 1 | 0.533 |
MRCKA |
0.838 | 0.028 | -3 | 0.792 |
HUNK |
0.838 | -0.081 | 2 | 0.863 |
MOK |
0.838 | 0.081 | 1 | 0.645 |
JNK1 |
0.837 | -0.015 | 1 | 0.495 |
MRCKB |
0.837 | 0.040 | -3 | 0.777 |
MARK4 |
0.837 | 0.020 | 4 | 0.862 |
DCAMKL2 |
0.837 | -0.029 | -3 | 0.839 |
NEK7 |
0.837 | -0.064 | -3 | 0.881 |
CDK14 |
0.836 | 0.043 | 1 | 0.566 |
DNAPK |
0.836 | -0.049 | 1 | 0.543 |
CDK1 |
0.836 | 0.014 | 1 | 0.513 |
PLK3 |
0.835 | -0.082 | 2 | 0.825 |
CAMK2D |
0.835 | -0.003 | -3 | 0.878 |
GSK3B |
0.835 | 0.048 | 4 | 0.517 |
ERK7 |
0.835 | 0.034 | 2 | 0.592 |
HIPK3 |
0.834 | 0.017 | 1 | 0.607 |
NEK6 |
0.834 | 0.038 | -2 | 0.904 |
TBK1 |
0.834 | -0.099 | 1 | 0.641 |
GSK3A |
0.834 | 0.091 | 4 | 0.527 |
DRAK1 |
0.834 | -0.120 | 1 | 0.624 |
ULK2 |
0.834 | -0.112 | 2 | 0.835 |
IRE1 |
0.833 | -0.009 | 1 | 0.714 |
TGFBR2 |
0.833 | -0.035 | -2 | 0.840 |
GRK1 |
0.832 | 0.062 | -2 | 0.817 |
ATM |
0.832 | -0.064 | 1 | 0.627 |
CHAK1 |
0.832 | -0.150 | 2 | 0.822 |
DYRK1A |
0.832 | 0.017 | 1 | 0.611 |
AMPKA2 |
0.832 | 0.019 | -3 | 0.858 |
MYLK4 |
0.832 | 0.007 | -2 | 0.797 |
AKT2 |
0.831 | 0.072 | -3 | 0.730 |
PAK1 |
0.831 | 0.031 | -2 | 0.804 |
PKCZ |
0.831 | 0.032 | 2 | 0.832 |
CLK4 |
0.831 | 0.059 | -3 | 0.808 |
SMG1 |
0.831 | -0.075 | 1 | 0.649 |
GRK2 |
0.831 | -0.093 | -2 | 0.749 |
RSK2 |
0.830 | 0.086 | -3 | 0.812 |
WNK3 |
0.830 | -0.176 | 1 | 0.710 |
PAK2 |
0.830 | -0.026 | -2 | 0.789 |
PKCA |
0.830 | 0.043 | 2 | 0.784 |
HIPK4 |
0.829 | 0.053 | 1 | 0.645 |
IRE2 |
0.829 | -0.024 | 2 | 0.797 |
IRAK1 |
0.828 | -0.171 | -1 | 0.757 |
CDK6 |
0.828 | 0.006 | 1 | 0.560 |
CDK18 |
0.827 | 0.056 | 1 | 0.525 |
NDR1 |
0.827 | 0.068 | -3 | 0.874 |
DYRK1B |
0.827 | 0.021 | 1 | 0.557 |
TTBK2 |
0.827 | -0.154 | 2 | 0.775 |
P90RSK |
0.827 | 0.047 | -3 | 0.819 |
SGK1 |
0.827 | 0.072 | -3 | 0.652 |
IKKB |
0.827 | -0.006 | -2 | 0.787 |
SRPK1 |
0.827 | 0.089 | -3 | 0.801 |
MELK |
0.827 | -0.004 | -3 | 0.840 |
IKKE |
0.827 | -0.131 | 1 | 0.624 |
CAMK2B |
0.826 | 0.028 | 2 | 0.826 |
CDK3 |
0.826 | 0.048 | 1 | 0.481 |
NIM1 |
0.825 | 0.016 | 3 | 0.795 |
PRKD1 |
0.825 | 0.124 | -3 | 0.864 |
DYRK3 |
0.825 | 0.034 | 1 | 0.604 |
CAMK4 |
0.825 | -0.074 | -3 | 0.855 |
PKCH |
0.825 | -0.037 | 2 | 0.779 |
CDK2 |
0.825 | -0.024 | 1 | 0.590 |
PKCB |
0.824 | 0.033 | 2 | 0.793 |
SRPK3 |
0.824 | 0.036 | -3 | 0.776 |
PAK3 |
0.824 | -0.020 | -2 | 0.803 |
CDK17 |
0.824 | -0.002 | 1 | 0.456 |
AURB |
0.823 | 0.053 | -2 | 0.679 |
CDK16 |
0.823 | 0.029 | 1 | 0.485 |
PLK2 |
0.823 | -0.034 | -3 | 0.811 |
PDHK3_TYR |
0.822 | 0.213 | 4 | 0.932 |
AKT1 |
0.822 | 0.056 | -3 | 0.748 |
CAMK1D |
0.822 | 0.004 | -3 | 0.725 |
CDK13 |
0.822 | -0.020 | 1 | 0.548 |
GRK4 |
0.822 | -0.108 | -2 | 0.858 |
PLK4 |
0.821 | -0.057 | 2 | 0.684 |
CHK2 |
0.821 | 0.003 | -3 | 0.671 |
CDK4 |
0.821 | -0.039 | 1 | 0.504 |
MAPKAPK3 |
0.821 | -0.012 | -3 | 0.814 |
HIPK2 |
0.821 | 0.045 | 1 | 0.504 |
DYRK4 |
0.821 | 0.027 | 1 | 0.513 |
QIK |
0.821 | -0.066 | -3 | 0.872 |
PKACG |
0.820 | 0.044 | -2 | 0.769 |
CAMK2A |
0.820 | 0.018 | 2 | 0.845 |
CDK8 |
0.820 | -0.015 | 1 | 0.561 |
RSK3 |
0.820 | 0.056 | -3 | 0.808 |
PKCG |
0.820 | 0.002 | 2 | 0.800 |
CLK1 |
0.819 | 0.061 | -3 | 0.781 |
PRKD3 |
0.819 | 0.025 | -3 | 0.782 |
CAMK1G |
0.819 | -0.016 | -3 | 0.800 |
IKKA |
0.819 | 0.026 | -2 | 0.778 |
CDK12 |
0.819 | -0.026 | 1 | 0.513 |
MSK1 |
0.819 | 0.042 | -3 | 0.794 |
SSTK |
0.819 | -0.033 | 4 | 0.828 |
MARK2 |
0.818 | -0.028 | 4 | 0.760 |
GCN2 |
0.818 | -0.099 | 2 | 0.851 |
RIPK2 |
0.818 | -0.273 | 1 | 0.637 |
CDK7 |
0.818 | -0.018 | 1 | 0.573 |
QSK |
0.817 | 0.015 | 4 | 0.833 |
PKCE |
0.817 | 0.022 | 2 | 0.783 |
STK33 |
0.816 | -0.154 | 2 | 0.682 |
RSK4 |
0.816 | 0.063 | -3 | 0.787 |
CDK10 |
0.816 | 0.040 | 1 | 0.554 |
NDR2 |
0.816 | 0.100 | -3 | 0.885 |
MAP2K4_TYR |
0.816 | 0.160 | -1 | 0.896 |
PKCI |
0.815 | -0.019 | 2 | 0.799 |
PKMYT1_TYR |
0.815 | 0.192 | 3 | 0.870 |
AURC |
0.814 | 0.106 | -2 | 0.682 |
CDK9 |
0.814 | -0.040 | 1 | 0.557 |
PKG2 |
0.814 | 0.031 | -2 | 0.701 |
ULK1 |
0.814 | -0.190 | -3 | 0.849 |
PRKD2 |
0.814 | 0.091 | -3 | 0.807 |
MNK1 |
0.814 | 0.003 | -2 | 0.827 |
MNK2 |
0.814 | 0.016 | -2 | 0.819 |
MSK2 |
0.814 | 0.000 | -3 | 0.791 |
PKCT |
0.814 | -0.022 | 2 | 0.785 |
MAP2K6_TYR |
0.813 | 0.114 | -1 | 0.894 |
AURA |
0.813 | 0.014 | -2 | 0.649 |
CLK2 |
0.813 | 0.131 | -3 | 0.793 |
MARK3 |
0.812 | -0.012 | 4 | 0.790 |
LATS2 |
0.812 | 0.007 | -5 | 0.782 |
PKACB |
0.812 | 0.089 | -2 | 0.700 |
PDHK4_TYR |
0.811 | 0.038 | 2 | 0.918 |
BCKDK |
0.811 | -0.149 | -1 | 0.818 |
MARK1 |
0.811 | -0.071 | 4 | 0.810 |
TESK1_TYR |
0.811 | -0.053 | 3 | 0.893 |
BMPR2_TYR |
0.809 | 0.001 | -1 | 0.895 |
SBK |
0.809 | 0.049 | -3 | 0.605 |
MAP2K7_TYR |
0.809 | -0.108 | 2 | 0.905 |
PDHK1_TYR |
0.808 | -0.011 | -1 | 0.902 |
MAPKAPK2 |
0.808 | 0.041 | -3 | 0.770 |
P70S6K |
0.808 | 0.002 | -3 | 0.747 |
CK1D |
0.808 | 0.028 | -3 | 0.560 |
CDK19 |
0.807 | -0.005 | 1 | 0.532 |
CAMK1A |
0.807 | 0.003 | -3 | 0.691 |
NUAK1 |
0.807 | -0.017 | -3 | 0.825 |
GRK3 |
0.807 | -0.063 | -2 | 0.704 |
EPHA6 |
0.807 | 0.028 | -1 | 0.875 |
LIMK2_TYR |
0.806 | 0.028 | -3 | 0.923 |
BLK |
0.806 | 0.304 | -1 | 0.844 |
PINK1_TYR |
0.806 | -0.130 | 1 | 0.737 |
PHKG1 |
0.805 | -0.053 | -3 | 0.865 |
SIK |
0.805 | -0.010 | -3 | 0.799 |
YES1 |
0.805 | 0.187 | -1 | 0.850 |
FGR |
0.805 | 0.183 | 1 | 0.828 |
FAM20C |
0.804 | 0.107 | 2 | 0.638 |
EPHB4 |
0.804 | 0.029 | -1 | 0.852 |
LCK |
0.804 | 0.268 | -1 | 0.839 |
CK2A2 |
0.803 | 0.030 | 1 | 0.600 |
AKT3 |
0.803 | 0.069 | -3 | 0.669 |
CK1A2 |
0.802 | 0.021 | -3 | 0.559 |
SRPK2 |
0.802 | 0.051 | -3 | 0.722 |
ABL2 |
0.802 | 0.055 | -1 | 0.821 |
HCK |
0.801 | 0.156 | -1 | 0.835 |
TTBK1 |
0.801 | -0.177 | 2 | 0.694 |
TNK2 |
0.800 | 0.092 | 3 | 0.791 |
RET |
0.800 | -0.146 | 1 | 0.695 |
PKACA |
0.800 | 0.060 | -2 | 0.649 |
TXK |
0.800 | 0.060 | 1 | 0.734 |
YANK3 |
0.799 | -0.045 | 2 | 0.462 |
LIMK1_TYR |
0.799 | -0.077 | 2 | 0.897 |
ABL1 |
0.799 | 0.053 | -1 | 0.814 |
CK1E |
0.799 | 0.025 | -3 | 0.609 |
MST1R |
0.799 | -0.124 | 3 | 0.832 |
TYK2 |
0.798 | -0.154 | 1 | 0.703 |
PKN1 |
0.798 | -0.018 | -3 | 0.761 |
PAK6 |
0.798 | 0.033 | -2 | 0.729 |
ROS1 |
0.797 | -0.098 | 3 | 0.789 |
FYN |
0.797 | 0.215 | -1 | 0.819 |
TYRO3 |
0.796 | -0.115 | 3 | 0.814 |
JAK2 |
0.796 | -0.147 | 1 | 0.688 |
DDR1 |
0.796 | -0.135 | 4 | 0.858 |
SNRK |
0.796 | -0.197 | 2 | 0.733 |
FER |
0.795 | -0.061 | 1 | 0.774 |
CSF1R |
0.795 | -0.118 | 3 | 0.813 |
CK2A1 |
0.795 | 0.011 | 1 | 0.570 |
KIS |
0.795 | 0.043 | 1 | 0.589 |
MAPKAPK5 |
0.794 | -0.099 | -3 | 0.762 |
EPHA4 |
0.794 | -0.031 | 2 | 0.824 |
EPHB3 |
0.794 | 0.001 | -1 | 0.834 |
BRSK2 |
0.794 | -0.091 | -3 | 0.851 |
SRMS |
0.793 | -0.058 | 1 | 0.740 |
EPHB2 |
0.792 | -0.002 | -1 | 0.833 |
JAK3 |
0.792 | -0.142 | 1 | 0.676 |
ITK |
0.792 | -0.028 | -1 | 0.807 |
BRSK1 |
0.792 | -0.063 | -3 | 0.832 |
EPHB1 |
0.791 | -0.090 | 1 | 0.725 |
INSRR |
0.791 | -0.110 | 3 | 0.768 |
PRKX |
0.790 | 0.106 | -3 | 0.722 |
KDR |
0.789 | -0.090 | 3 | 0.783 |
PHKG2 |
0.788 | -0.072 | -3 | 0.828 |
MERTK |
0.788 | -0.057 | 3 | 0.796 |
TNNI3K_TYR |
0.788 | -0.028 | 1 | 0.717 |
KIT |
0.787 | -0.146 | 3 | 0.816 |
JAK1 |
0.787 | -0.078 | 1 | 0.640 |
FGFR2 |
0.787 | -0.180 | 3 | 0.820 |
SRC |
0.786 | 0.150 | -1 | 0.816 |
YANK2 |
0.786 | -0.077 | 2 | 0.477 |
BMX |
0.786 | -0.046 | -1 | 0.742 |
TNK1 |
0.786 | -0.068 | 3 | 0.795 |
LYN |
0.786 | 0.087 | 3 | 0.739 |
PDGFRB |
0.786 | -0.190 | 3 | 0.822 |
FLT3 |
0.785 | -0.180 | 3 | 0.807 |
AXL |
0.785 | -0.112 | 3 | 0.802 |
MET |
0.785 | -0.098 | 3 | 0.807 |
NEK10_TYR |
0.784 | -0.154 | 1 | 0.587 |
EPHA7 |
0.784 | -0.071 | 2 | 0.827 |
BTK |
0.783 | -0.123 | -1 | 0.770 |
FLT1 |
0.782 | -0.111 | -1 | 0.844 |
EPHA3 |
0.782 | -0.090 | 2 | 0.800 |
TEC |
0.782 | -0.104 | -1 | 0.748 |
PAK5 |
0.782 | -0.023 | -2 | 0.663 |
FGFR1 |
0.782 | -0.200 | 3 | 0.788 |
WEE1_TYR |
0.781 | -0.084 | -1 | 0.767 |
LTK |
0.781 | -0.123 | 3 | 0.762 |
TEK |
0.780 | -0.203 | 3 | 0.757 |
FRK |
0.780 | -0.099 | -1 | 0.846 |
PTK6 |
0.779 | -0.144 | -1 | 0.736 |
NTRK1 |
0.779 | -0.184 | -1 | 0.826 |
ERBB2 |
0.779 | -0.166 | 1 | 0.661 |
EPHA1 |
0.779 | -0.093 | 3 | 0.788 |
PTK2B |
0.779 | -0.047 | -1 | 0.783 |
EPHA5 |
0.778 | -0.054 | 2 | 0.808 |
ALK |
0.777 | -0.176 | 3 | 0.734 |
PDGFRA |
0.777 | -0.265 | 3 | 0.819 |
FGFR3 |
0.777 | -0.176 | 3 | 0.795 |
NTRK3 |
0.776 | -0.119 | -1 | 0.782 |
INSR |
0.776 | -0.148 | 3 | 0.750 |
EPHA8 |
0.776 | -0.070 | -1 | 0.822 |
DDR2 |
0.775 | -0.067 | 3 | 0.764 |
PTK2 |
0.775 | 0.007 | -1 | 0.804 |
EGFR |
0.774 | -0.093 | 1 | 0.590 |
NTRK2 |
0.774 | -0.199 | 3 | 0.773 |
PAK4 |
0.773 | -0.007 | -2 | 0.667 |
FLT4 |
0.773 | -0.210 | 3 | 0.778 |
MATK |
0.772 | -0.121 | -1 | 0.757 |
SYK |
0.770 | -0.035 | -1 | 0.792 |
FGFR4 |
0.769 | -0.111 | -1 | 0.786 |
CSK |
0.769 | -0.154 | 2 | 0.831 |
CK1G1 |
0.769 | -0.007 | -3 | 0.603 |
PKG1 |
0.767 | -0.017 | -2 | 0.618 |
EPHA2 |
0.766 | -0.082 | -1 | 0.791 |
MUSK |
0.763 | -0.140 | 1 | 0.610 |
ERBB4 |
0.762 | -0.075 | 1 | 0.599 |
IGF1R |
0.761 | -0.156 | 3 | 0.687 |
CK1G3 |
0.755 | -0.034 | -3 | 0.422 |
ZAP70 |
0.750 | -0.047 | -1 | 0.724 |
FES |
0.748 | -0.155 | -1 | 0.720 |
CK1G2 |
0.736 | -0.033 | -3 | 0.519 |
CK1A |
0.733 | -0.010 | -3 | 0.468 |