Motif 313 (n=254)

Position-wise Probabilities

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uniprot genes site source protein function
A6NJT0 UNCX S449 ochoa Homeobox protein unc-4 homolog (Homeobox protein Uncx4.1) Transcription factor involved in somitogenesis and neurogenesis. Required for the maintenance and differentiation of particular elements of the axial skeleton. May act upstream of PAX9. Plays a role in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and to deliver hormones for control of peripheral functions (By similarity). {ECO:0000250}.
A6NJZ7 RIMBP3C S1228 ochoa RIMS-binding protein 3C (RIM-BP3.C) (RIMS-binding protein 3.3) (RIM-BP3.3) Probable component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development. {ECO:0000250|UniProtKB:Q3V0F0}.
A6NNM3 RIMBP3B S1228 ochoa RIMS-binding protein 3B (RIM-BP3.B) (RIMS-binding protein 3.2) (RIM-BP3.2) Probable component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development. {ECO:0000250|UniProtKB:Q3V0F0}.
D6RIA3 C4orf54 S687 ochoa Uncharacterized protein C4orf54 (Familial obliterative portal venopathy) None
O00151 PDLIM1 S250 ochoa PDZ and LIM domain protein 1 (C-terminal LIM domain protein 1) (Elfin) (LIM domain protein CLP-36) Cytoskeletal protein that may act as an adapter that brings other proteins (like kinases) to the cytoskeleton (PubMed:10861853). Involved in assembly, disassembly and directioning of stress fibers in fibroblasts. Required for the localization of ACTN1 and PALLD to stress fibers. Required for cell migration and in maintaining cell polarity of fibroblasts (By similarity). {ECO:0000250|UniProtKB:P52944, ECO:0000269|PubMed:10861853}.
O00512 BCL9 S904 ochoa B-cell CLL/lymphoma 9 protein (B-cell lymphoma 9 protein) (Bcl-9) (Protein legless homolog) Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:11955446}.
O00562 PITPNM1 S382 ochoa|psp Membrane-associated phosphatidylinositol transfer protein 1 (Drosophila retinal degeneration B homolog) (Phosphatidylinositol transfer protein, membrane-associated 1) (PITPnm 1) (Pyk2 N-terminal domain-interacting receptor 2) (NIR-2) Catalyzes the transfer of phosphatidylinositol (PI) between membranes (PubMed:10531358, PubMed:22822086). Binds PI, phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC (PubMed:22822086). Regulates RHOA activity, and plays a role in cytoskeleton remodeling (PubMed:11909959). Necessary for normal completion of cytokinesis (PubMed:15125835). Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus (PubMed:15723057). Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus (PubMed:15545272). Required for protein export from the endoplasmic reticulum and the Golgi (PubMed:15723057). Binds calcium ions (PubMed:10022914). {ECO:0000269|PubMed:10022914, ECO:0000269|PubMed:10531358, ECO:0000269|PubMed:11909959, ECO:0000269|PubMed:15545272, ECO:0000269|PubMed:15723057, ECO:0000269|PubMed:22822086}.
O14874 BCKDK S339 ochoa Branched-chain alpha-ketoacid dehydrogenase kinase (BCKDH kinase) (BCKDHKIN) (BDK) (EC 2.7.11.1) ([3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial) (EC 2.7.11.4) Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (PubMed:24449431, PubMed:29779826, PubMed:37558654). Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826). {ECO:0000269|PubMed:24449431, ECO:0000269|PubMed:29779826, ECO:0000269|PubMed:37558654}.
O14939 PLD2 S134 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}.
O15156 ZBTB7B S480 ochoa Zinc finger and BTB domain-containing protein 7B (Krueppel-related zinc finger protein cKrox) (hcKrox) (T-helper-inducing POZ/Krueppel-like factor) (Zinc finger and BTB domain-containing protein 15) (Zinc finger protein 67 homolog) (Zfp-67) (Zinc finger protein 857B) (Zinc finger protein Th-POK) Transcription regulator that acts as a key regulator of lineage commitment of immature T-cell precursors. Exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively. Cross-antagonism between ZBTB7B and CBF complexes are determinative to CD4 versus CD8 cell fate decision. Suppresses RUNX3 expression and imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine signaling. induces, as a transcriptional activator, SOCS genes expression which represses RUNX3 expression and promotes the CD4+ lineage fate. During CD4 lineage commitment, associates with multiple sites at the CD8 locus, acting as a negative regulator of the CD8 promoter and enhancers by epigenetic silencing through the recruitment of class II histone deacetylases, such as HDAC4 and HDAC5, to these loci. Regulates the development of IL17-producing CD1d-restricted naural killer (NK) T cells. Also functions as an important metabolic regulator in the lactating mammary glands. Critical feed-forward regulator of insulin signaling in mammary gland lactation, directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling (By similarity). Transcriptional repressor of the collagen COL1A1 and COL1A2 genes. May also function as a repressor of fibronectin and possibly other extracellular matrix genes (PubMed:9370309). Potent driver of brown fat development, thermogenesis and cold-induced beige fat formation. Recruits the brown fat lncRNA 1 (Blnc1):HNRNPU ribonucleoprotein complex to activate thermogenic gene expression in brown and beige adipocytes (By similarity). {ECO:0000250|UniProtKB:Q64321, ECO:0000269|PubMed:9370309}.
O15169 AXIN1 S511 ochoa Axin-1 (Axis inhibition protein 1) (hAxin) Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453, PubMed:28829046). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway (PubMed:12192039). In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (PubMed:16601693). Also a component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development (PubMed:17210684). Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation (PubMed:17210684). {ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17210684, ECO:0000269|PubMed:27098453, ECO:0000269|PubMed:28546513}.
O15297 PPM1D S85 ochoa|psp Protein phosphatase 1D (EC 3.1.3.16) (Protein phosphatase 2C isoform delta) (PP2C-delta) (Protein phosphatase magnesium-dependent 1 delta) (p53-induced protein phosphatase 1) Involved in the negative regulation of p53 expression (PubMed:23242139). Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins (PubMed:15870257, PubMed:16311512). Mediates MAPK14 dephosphorylation and inactivation (PubMed:21283629). Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity (By similarity). {ECO:0000250|UniProtKB:Q9QZ67, ECO:0000269|PubMed:15870257, ECO:0000269|PubMed:16311512, ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:23242139}.
O43491 EPB41L2 S806 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}.
O43586 PSTPIP1 S327 ochoa Proline-serine-threonine phosphatase-interacting protein 1 (PEST phosphatase-interacting protein 1) (CD2-binding protein 1) (H-PIP) Involved in regulation of the actin cytoskeleton. May regulate WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allow PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation (By similarity). Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2. Also has a role in innate immunity and the inflammatory response. Recruited to inflammasomes by MEFV. Induces formation of pyroptosomes, large supramolecular structures composed of oligomerized PYCARD dimers which form prior to inflammatory apoptosis. Binding to MEFV allows MEFV to bind to PYCARD and facilitates pyroptosome formation. Regulates endocytosis and cell migration in neutrophils. {ECO:0000250, ECO:0000269|PubMed:17964261, ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:19109554, ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:9857189}.
O43633 CHMP2A S203 ochoa Charged multivesicular body protein 2a (Chromatin-modifying protein 2a) (CHMP2a) (Putative breast adenocarcinoma marker BC-2) (Vacuolar protein sorting-associated protein 2-1) (Vps2-1) (hVps2-1) 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 (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Recruited to the reforming nuclear envelope (NE) during anaphase by LEMD2 (PubMed:28242692). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. {ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:28242692, ECO:0000305}.; FUNCTION: (Microbial infection) The ESCRT machinery functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844}.
O60264 SMARCA5 S47 ochoa SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin A5) (EC 3.6.4.-) (Sucrose nonfermenting protein 2 homolog) (hSNF2H) ATPase that possesses intrinsic ATP-dependent nucleosome-remodeling activity (PubMed:12972596, PubMed:28801535). Catalytic subunit of 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; this may require intact histone H4 tails (PubMed:10880450, PubMed:12198550, PubMed:12434153, PubMed:12972596, PubMed:23911928, PubMed:28801535). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:28801535). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (PubMed:28801535). The BAZ1A/ACF1-, BAZ1B/WSTF-, BAZ2A/TIP5- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner (PubMed:14759371, PubMed:15543136, PubMed:28801535). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Binds to core histones together with RSF1, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Involved in DNA replication and together with BAZ1A/ACF1 is required for replication of pericentric heterochromatin in S-phase (PubMed:12434153). Probably plays a role in repression of RNA polymerase I dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter (By similarity). Essential component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex), a chromatin-remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure (PubMed:11980720, PubMed:15543136). 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 histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes (By similarity). Essential component of NoRC-5 ISWI chromatin-remodeling complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity). {ECO:0000250|UniProtKB:Q91ZW3, ECO:0000269|PubMed:10880450, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:12198550, ECO:0000269|PubMed:12434153, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:14759371, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:23911928, ECO:0000269|PubMed:28801535}.
O60716 CTNND1 S617 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}.
O75533 SF3B1 S190 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}.
O75955 FLOT1 S315 psp Flotillin-1 May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles.
O76094 SRP72 S610 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}.
O94811 TPPP S45 ochoa Tubulin polymerization-promoting protein (TPPP) (EC 3.6.5.-) (25 kDa brain-specific protein) (TPPP/p25) (p24) (p25-alpha) Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath (PubMed:31522887). Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath (PubMed:31522887, PubMed:33831707). Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes (PubMed:31522887). Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear (PubMed:21316364, PubMed:21995432). In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network (PubMed:17105200, PubMed:17693641, PubMed:18028908, PubMed:26289831). Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407). Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility (PubMed:23093407). Plays a role in cell proliferation by regulating the G1/S-phase transition (PubMed:23355470). Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2 (PubMed:22328514). {ECO:0000269|PubMed:17105200, ECO:0000269|PubMed:17693641, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:20308065, ECO:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:26289831, ECO:0000269|PubMed:31522887}.
O94819 KBTBD11 S87 ochoa Kelch repeat and BTB domain-containing protein 11 (Chronic myelogenous leukemia-associated protein) (Kelch domain-containing protein 7B) None
O95071 UBR5 S1728 ochoa E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}.
O95359 TACC2 S1283 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 S3274 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}.
O95817 BAG3 S264 ochoa BAG family molecular chaperone regulator 3 (BAG-3) (Bcl-2-associated athanogene 3) (Bcl-2-binding protein Bis) (Docking protein CAIR-1) Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g. HSPA1A/HSP70 or HSPA8/HSC70, and small heat shock proteins (sHSPs), e.g. HSPB8 (PubMed:27884606, PubMed:30559338). Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from HSP70s, thereby triggering client protein release (PubMed:27884606, PubMed:30559338). Nucleotide release is mediated via BAG3 binding to the nucleotide-binding domain (NBD) of HSP70s, whereas client release is mediated via binding to the substrate-binding domain (SBD) (PubMed:27474739, PubMed:9873016). Has anti-apoptotic activity (PubMed:10597216). Plays a role in the HSF1 nucleocytoplasmic transport (PubMed:26159920). {ECO:0000269|PubMed:10597216, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27884606, ECO:0000269|PubMed:30559338, ECO:0000269|PubMed:9873016}.
O95861 BPNT1 S240 ochoa 3'(2'),5'-bisphosphate nucleotidase 1 (EC 3.1.3.7) (3'-phosphoadenosine 5'-phosphate phosphatase) (PAP phosphatase) (Bisphosphate 3'-nucleotidase 1) (BPntase 1) (HsPIP) (Inositol-polyphosphate 1-phosphatase) (EC 3.1.3.57) Phosphatase that converts 3'(2')-phosphoadenosine 5'-phosphate (PAP) to AMP and inositol 1,4-bisphosphate (Ins(1,4)P2) to inositol 4-phosphate (PubMed:10675562). Is also able to hydrolyze adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to adenosine 5'-phosphosulfate (APS) (By similarity). Probably prevents the toxic accumulation of PAP, a compound which inhibits a variety of proteins, including PAPS-utilizing enzymes such as sulfotransferases, and RNA processing enzymes. Could also play a role in inositol recycling and phosphoinositide metabolism. Is not active on 3'-AMP, inositol-1-phosphate and inositol-1,4,5-triphosphate (PubMed:10675562). {ECO:0000250|UniProtKB:Q9Z1N4, ECO:0000269|PubMed:10675562}.
O96008 TOMM40 S64 ochoa Mitochondrial import receptor subunit TOM40 homolog (Protein Haymaker) (Translocase of outer membrane 40 kDa subunit homolog) (p38.5) Channel-forming protein essential for import of protein precursors into mitochondria (PubMed:15644312, PubMed:31206022). Plays a role in the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) by forming a complex with BCAP31 and mediating the translocation of Complex I components from the cytosol to the mitochondria (PubMed:31206022). {ECO:0000269|PubMed:15644312, ECO:0000269|PubMed:31206022}.
O96013 PAK4 S195 ochoa Serine/threonine-protein kinase PAK 4 (EC 2.7.11.1) (p21-activated kinase 4) (PAK-4) Serine/threonine-protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell adhesion turnover, cell migration, growth, proliferation or cell survival (PubMed:26598620). Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Promotes kinase-independent stabilization of RHOU, thereby contributing to focal adhesion disassembly during cell migration (PubMed:26598620). {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26598620, ECO:0000269|PubMed:26607847}.
P02686 MBP S153 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}.
P04792 HSPB1 S65 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}.
P07199 CENPB S156 ochoa Major centromere autoantigen B (Centromere protein B) (CENP-B) Interacts with centromeric heterochromatin in chromosomes and binds to a specific 17 bp subset of alphoid satellite DNA, called the CENP-B box (PubMed:11726497). May organize arrays of centromere satellite DNA into a higher-order structure which then directs centromere formation and kinetochore assembly in mammalian chromosomes (Probable). {ECO:0000269|PubMed:11726497, ECO:0000305}.
P08195 SLC3A2 S129 ochoa Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}.
P08195 SLC3A2 S134 ochoa Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}.
P08559 PDHA1 S239 psp Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (EC 1.2.4.1) (PDHE1-A type I) The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}.
P08913 ADRA2A S375 psp Alpha-2A adrenergic receptor (Alpha-2 adrenergic receptor subtype C10) (Alpha-2A adrenoreceptor) (Alpha-2A adrenoceptor) (Alpha-2AAR) Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. {ECO:0000269|PubMed:23105096}.
P09661 SNRPA1 S212 ochoa U2 small nuclear ribonucleoprotein A' (U2 snRNP A') Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:27035939, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (PubMed:27035939, PubMed:32494006, PubMed:9716128). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:27035939, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:9716128}.
P0C671 BNIP5 S463 ochoa Protein BNIP5 None
P0C7T5 ATXN1L S251 ochoa Ataxin-1-like (Brother of ataxin-1) (Brother of ATXN1) Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression (PubMed:21475249). Can suppress ATXN1 cytotoxicity in spinocerebellar ataxia type 1 (SCA1). In concert with CIC and ATXN1, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P0C7T6, ECO:0000269|PubMed:21475249}.
P10588 NR2F6 S34 ochoa Nuclear receptor subfamily 2 group F member 6 (V-erbA-related protein 2) (EAR-2) Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). {ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:10713182, ECO:0000269|PubMed:11682620, ECO:0000269|PubMed:18701084}.
P10588 NR2F6 S40 ochoa Nuclear receptor subfamily 2 group F member 6 (V-erbA-related protein 2) (EAR-2) Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). {ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:10713182, ECO:0000269|PubMed:11682620, ECO:0000269|PubMed:18701084}.
P10588 NR2F6 S156 ochoa Nuclear receptor subfamily 2 group F member 6 (V-erbA-related protein 2) (EAR-2) Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). {ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:10713182, ECO:0000269|PubMed:11682620, ECO:0000269|PubMed:18701084}.
P13164 IFITM1 S80 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}.
P15884 TCF4 S330 ochoa Transcription factor 4 (TCF-4) (Class B basic helix-loop-helix protein 19) (bHLHb19) (Immunoglobulin transcription factor 2) (ITF-2) (SL3-3 enhancer factor 2) (SEF-2) Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'. {ECO:0000250}.
P16144 ITGB4 S809 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}.
P16989 YBX3 S72 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}.
P17600 SYN1 S67 ochoa Synapsin-1 (Brain protein 4.1) (Synapsin I) Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (PubMed:21441247, PubMed:23406870). Also involved in the regulation of axon outgrowth and synaptogenesis (By similarity). The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level (By similarity). {ECO:0000250|UniProtKB:O88935, ECO:0000250|UniProtKB:P09951, ECO:0000269|PubMed:21441247, ECO:0000269|PubMed:23406870}.
P17677 GAP43 S130 ochoa Neuromodulin (Axonal membrane protein GAP-43) (Growth-associated protein 43) (Neural phosphoprotein B-50) (pp46) This protein is associated with nerve growth. It is a major component of the motile 'growth cones' that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction. {ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:21152083}.
P18031 PTPN1 S386 ochoa|psp Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}.
P18206 VCL S52 ochoa Vinculin (Metavinculin) (MV) Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}.
P18206 VCL S272 ochoa Vinculin (Metavinculin) (MV) Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}.
P19484 TFEB S122 ochoa|psp Transcription factor EB (Class E basic helix-loop-helix protein 35) (bHLHe35) Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:30120233, PubMed:31672913, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823, PubMed:36749723, PubMed:37079666). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (PubMed:19556463, PubMed:22692423). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica: infection promotes itaconate production, leading to alkylation, resulting in nuclear localization and transcription factor activity (PubMed:35662396). Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response (PubMed:35662396). In association with ACSS2, promotes the expression of genes involved in lysosome biogenesis and both autophagy upon glucose deprivation (PubMed:28552616). {ECO:0000250|UniProtKB:Q9R210, ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:36749723, ECO:0000269|PubMed:37079666}.
P21333 FLNA S2558 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}.
P21731 TBXA2R S145 psp Thromboxane A2 receptor (TXA2-R) (Prostanoid TP receptor) Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. {ECO:0000269|PubMed:8613548}.; FUNCTION: [Isoform 1]: Activates adenylyl cyclase. {ECO:0000269|PubMed:8613548}.; FUNCTION: [Isoform 2]: Inhibits adenylyl cyclase. {ECO:0000269|PubMed:8613548}.
P25098 GRK2 S29 psp Beta-adrenergic receptor kinase 1 (Beta-ARK-1) (EC 2.7.11.15) (G-protein coupled receptor kinase 2) Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (By similarity). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927). {ECO:0000250|UniProtKB:P21146, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:19715378, ECO:0000269|PubMed:30284927}.
P26232 CTNNA2 S262 ochoa Catenin alpha-2 (Alpha N-catenin) (Alpha-catenin-related protein) May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulation of cortical neuronal migration and neurite growth (PubMed:30013181). It acts as a negative regulator of Arp2/3 complex activity and Arp2/3-mediated actin polymerization (PubMed:30013181). It thereby suppresses excessive actin branching which would impair neurite growth and stability (PubMed:30013181). Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation (By similarity). {ECO:0000250|UniProtKB:Q61301, ECO:0000269|PubMed:30013181}.
P29692 EEF1D S37 ochoa Elongation factor 1-delta (EF-1-delta) (Antigen NY-CO-4) [Isoform 1]: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.; FUNCTION: [Isoform 2]: Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE).
P29966 MARCKS S26 ochoa Myristoylated alanine-rich C-kinase substrate (MARCKS) (Protein kinase C substrate, 80 kDa protein, light chain) (80K-L protein) (PKCSL) Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes (PubMed:23704996, PubMed:36009319). Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis (PubMed:23704996). During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages (PubMed:37949888). Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton (By similarity). Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P26645, ECO:0000250|UniProtKB:P30009, ECO:0000269|PubMed:23704996, ECO:0000269|PubMed:36009319, ECO:0000269|PubMed:37949888}.
P29966 MARCKS S52 ochoa Myristoylated alanine-rich C-kinase substrate (MARCKS) (Protein kinase C substrate, 80 kDa protein, light chain) (80K-L protein) (PKCSL) Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes (PubMed:23704996, PubMed:36009319). Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis (PubMed:23704996). During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages (PubMed:37949888). Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton (By similarity). Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P26645, ECO:0000250|UniProtKB:P30009, ECO:0000269|PubMed:23704996, ECO:0000269|PubMed:36009319, ECO:0000269|PubMed:37949888}.
P31629 HIVEP2 S1067 ochoa Transcription factor HIVEP2 (Human immunodeficiency virus type I enhancer-binding protein 2) (HIV-EP2) (MHC-binding protein 2) (MBP-2) This protein specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon-beta genes. It may act in T-cell activation.
P31939 ATIC S264 ochoa Bifunctional purine biosynthesis protein ATIC (AICAR transformylase/inosine monophosphate cyclohydrolase) (ATIC) [Cleaved into: Bifunctional purine biosynthesis protein ATIC, N-terminally processed] [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase) (AICAR formyltransferase) (AICAR transformylase); Inosine 5'-monophosphate cyclohydrolase (IMP cyclohydrolase) (EC 3.5.4.10) (IMP synthase) (Inosinicase)] Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571). {ECO:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:9378707}.
P33897 ABCD1 S58 ochoa ATP-binding cassette sub-family D member 1 (EC 3.1.2.-) (EC 7.6.2.-) (Adrenoleukodystrophy protein) (ALDP) ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed:15682271, PubMed:16946495, PubMed:18757502, PubMed:21145416, PubMed:23671276, PubMed:29397936, PubMed:33500543). Coupled to the ATP-dependent transporter activity also has a fatty acyl-CoA thioesterase activity (ACOT) and hydrolyzes VLCFA-CoA into VLCFA prior their ATP-dependent transport into peroxisomes, the ACOT activity is essential during this transport process (PubMed:29397936, PubMed:33500543). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:21145416, PubMed:23671276). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance. Also controls the cellular response to oxidative stress by regulating mitochondrial functions such as mitochondrial oxidative phosphorylation and depolarization. And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (By similarity). {ECO:0000250|UniProtKB:P48410, ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:15682271, ECO:0000269|PubMed:16946495, ECO:0000269|PubMed:18757502, ECO:0000269|PubMed:21145416, ECO:0000269|PubMed:23671276, ECO:0000269|PubMed:29397936, ECO:0000269|PubMed:33500543}.
P35221 CTNNA1 S264 ochoa Catenin alpha-1 (Alpha E-catenin) (Cadherin-associated protein) (Renal carcinoma antigen NY-REN-13) Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). May play a crucial role in cell differentiation. {ECO:0000250|UniProtKB:P26231, ECO:0000269|PubMed:25653389}.
P35568 IRS1 S1036 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}.
P35568 IRS1 S1057 psp Insulin receptor substrate 1 (IRS-1) Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:11171109, PubMed:8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}.
P35711 SOX5 S439 ochoa Transcription factor SOX-5 Transcription factor involved in chondrocytes differentiation and cartilage formation. Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes, such as COL2A1 and AGC1. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX6, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene. {ECO:0000250|UniProtKB:P35710}.
P36956 SREBF1 S1049 ochoa Sterol regulatory element-binding protein 1 (SREBP-1) (Class D basic helix-loop-helix protein 1) (bHLHd1) (Sterol regulatory element-binding transcription factor 1) [Cleaved into: Processed sterol regulatory element-binding protein 1 (Transcription factor SREBF1)] [Sterol regulatory element-binding protein 1]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:32322062}.; FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:12177166, PubMed:32322062, PubMed:8402897). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:12177166, PubMed:8402897). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:12177166, PubMed:32322062, PubMed:8402897). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8402897}.; FUNCTION: [Isoform SREBP-1A]: Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166, PubMed:32497488). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32497488}.; FUNCTION: [Isoform SREBP-1C]: Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166}.; FUNCTION: [Isoform SREBP-1aDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}.; FUNCTION: [Isoform SREBP-1cDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}.
P39019 RPS19 S59 psp Small ribosomal subunit protein eS19 (40S ribosomal protein S19) Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for pre-rRNA processing and maturation of 40S ribosomal subunits (PubMed:16990592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:16990592, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}.
P40424 PBX1 S136 ochoa Pre-B-cell leukemia transcription factor 1 (Homeobox protein PBX1) (Homeobox protein PRL) Transcription factor which binds the DNA sequence 5'-TGATTGAT-3' as part of a heterodimer with HOX proteins such as HOXA1, HOXA5, HOXB7 and HOXB8 (PubMed:9191052). Binds to the DNA sequence 5'-TGATTGAC-3' in complex with a nuclear factor which is not a class I HOX protein (PubMed:9191052). Has also been shown to bind the DNA sequence 5'-ATCAATCAA-3' cooperatively with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4 (PubMed:7791786, PubMed:8327485). Acts as a transcriptional activator of PF4 in complex with MEIS1 (PubMed:12609849). Also activates transcription of SOX3 in complex with MEIS1 by binding to the 5'-TGATTGAC-3' consensus sequence (By similarity). In natural killer cells, binds to the NFIL3 promoter and acts as a transcriptional activator of NFIL3, promoting natural killer cell development (By similarity). Plays a role in the cAMP-dependent regulation of CYP17A1 gene expression via its cAMP-regulatory sequence (CRS1) (By similarity). Probably in complex with MEIS2, involved in transcriptional regulation by KLF4 (PubMed:21746878). Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B (By similarity). Together with NKX2-5, required for spleen development through a mechanism that involves CDKN2B repression (By similarity). {ECO:0000250|UniProtKB:P41778, ECO:0000269|PubMed:12609849, ECO:0000269|PubMed:21746878, ECO:0000269|PubMed:7791786, ECO:0000269|PubMed:8327485, ECO:0000269|PubMed:9191052}.; FUNCTION: [Isoform PBX1b]: As part of a PDX1:PBX1b:MEIS2B complex in pancreatic acinar cells, is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. {ECO:0000250|UniProtKB:P41778}.
P40425 PBX2 S146 ochoa Pre-B-cell leukemia transcription factor 2 (Homeobox protein PBX2) (Protein G17) Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1. {ECO:0000269|PubMed:12609849}.
P49006 MARCKSL1 S22 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}.
P49006 MARCKSL1 S162 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}.
P49354 FNTA S49 ochoa Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (EC 2.5.1.58) (EC 2.5.1.59) (CAAX farnesyltransferase subunit alpha) (FTase-alpha) (Ras proteins prenyltransferase subunit alpha) (Type I protein geranyl-geranyltransferase subunit alpha) (GGTase-I-alpha) Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation. {ECO:0000269|PubMed:12036349, ECO:0000269|PubMed:12825937, ECO:0000269|PubMed:16893176, ECO:0000269|PubMed:19246009, ECO:0000269|PubMed:8419339, ECO:0000269|PubMed:8494894}.
P49841 GSK3B S389 ochoa|psp Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1) Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:11430833, PubMed:12554650, PubMed:14690523, PubMed:16484495, PubMed:1846781, PubMed:20937854, PubMed:9072970). Requires primed phosphorylation of the majority of its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:8397507). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:8397507). Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (PubMed:14690523). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (By similarity). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed:22514281). Phosphorylates SNAI1, leading to its ubiquitination and proteasomal degradation (PubMed:15448698, PubMed:15647282, PubMed:25827072, PubMed:29059170). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (By similarity). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110). Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2 complex component RICTOR at 'Ser-1235' in response to endoplasmic stress, inhibiting mTORC2 (PubMed:21343617). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (By similarity). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20067585, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:29059170, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}.
P51582 P2RY4 S333 psp P2Y purinoceptor 4 (P2Y4) (P2P) (Uridine nucleotide receptor) (UNR) Receptor for UTP and UDP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. Not activated by ATP or ADP.
P51608 MECP2 S80 ochoa|psp Methyl-CpG-binding protein 2 (MeCp-2 protein) (MeCp2) Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC). {ECO:0000250|UniProtKB:Q9Z2D6}.
P52948 NUP98 S494 psp Nuclear pore complex protein Nup98-Nup96 (EC 3.4.21.-) [Cleaved into: Nuclear pore complex protein Nup98 (98 kDa nucleoporin) (Nucleoporin Nup98) (Nup98); Nuclear pore complex protein Nup96 (96 kDa nucleoporin) (Nucleoporin Nup96) (Nup96)] Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC (PubMed:33097660). May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:33097660}.; FUNCTION: (Microbial infection) Interacts with HIV-1 capsid protein P24 and nucleocapsid protein P7 and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change Asn-74-Asp is reduced (in vitro) (PubMed:23523133). {ECO:0000269|PubMed:23523133}.
P55317 FOXA1 S331 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}.
P85037 FOXK1 S288 ochoa Forkhead box protein K1 (Myocyte nuclear factor) (MNF) Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:17670796). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity). Represses myogenic differentiation by inhibiting MEFC activity (By similarity). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK1-bound genes (PubMed:24634419, PubMed:30664650). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164, ECO:0000269|PubMed:30664650}.
P98174 FGD1 S205 ochoa|psp FYVE, RhoGEF and PH domain-containing protein 1 (Faciogenital dysplasia 1 protein) (Rho/Rac guanine nucleotide exchange factor FGD1) (Rho/Rac GEF) (Zinc finger FYVE domain-containing protein 3) Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:8969170}.
P98175 RBM10 S483 ochoa RNA-binding protein 10 (G patch domain-containing protein 9) (RNA-binding motif protein 10) (RNA-binding protein S1-1) (S1-1) Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). May be involved in post-transcriptional processing, most probably in mRNA splicing (PubMed:18315527). Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000250|UniProtKB:P70501, ECO:0000269|PubMed:18315527, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:28431233}.
Q00975 CACNA1B S745 ochoa Voltage-dependent N-type calcium channel subunit alpha-1B (Brain calcium channel III) (BIII) (Calcium channel, L type, alpha-1 polypeptide isoform 5) (Voltage-gated calcium channel subunit alpha Cav2.2) Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling (PubMed:25296916). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. Mediates Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). {ECO:0000250|UniProtKB:Q02294, ECO:0000269|PubMed:25296916}.; FUNCTION: [Isoform Alpha-1B-1]: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. {ECO:0000269|PubMed:1321501}.
Q01628 IFITM3 S101 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 S100 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}.
Q04637 EIF4G1 S1110 ochoa Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}.
Q04637 EIF4G1 S1209 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}.
Q12931 TRAP1 S194 ochoa Heat shock protein 75 kDa, mitochondrial (HSP 75) (Heat shock protein family C member 5) (TNFR-associated protein 1) (Tumor necrosis factor type 1 receptor-associated protein) (TRAP-1) Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. {ECO:0000269|PubMed:23525905, ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:23747254}.
Q12955 ANK3 S623 ochoa Ankyrin-3 (ANK-3) (Ankyrin-G) Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}.
Q13045 FLII S418 ochoa Protein flightless-1 homolog Is a regulator of actin polymerization, required for proper myofibril organization and regulation of the length of sarcomeric thin filaments (By similarity). It also plays a role in the assembly of cardiomyocyte cell adhesion complexes (By similarity). Regulates cytoskeletal rearrangements involved in cytokinesis and cell migration, by inhibiting Rac1-dependent paxillin phosphorylation (By similarity). May play a role as coactivator in transcriptional activation by hormone-activated nuclear receptors (NR) and acts in cooperation with NCOA2 and CARM1 (PubMed:14966289). Involved in estrogen hormone signaling. {ECO:0000250|UniProtKB:Q9JJ28, ECO:0000269|PubMed:14966289}.
Q13118 KLF10 S206 ochoa|psp Krueppel-like factor 10 (EGR-alpha) (Transforming growth factor-beta-inducible early growth response protein 1) (TGFB-inducible early growth response protein 1) (TIEG-1) Transcriptional repressor which binds to the consensus sequence 5'-GGTGTG-3'. Plays a role in the regulation of the circadian clock; binds to the GC box sequence in the promoter of the core clock component ARTNL/BMAL1 and represses its transcriptional activity. Regulates the circadian expression of genes involved in lipogenesis, gluconeogenesis, and glycolysis in the liver. Represses the expression of PCK2, a rate-limiting step enzyme of gluconeogenesis (By similarity). May play a role in the cell cycle regulation. {ECO:0000250|UniProtKB:O89091, ECO:0000269|PubMed:8584037}.
Q13151 HNRNPA0 S68 ochoa Heterogeneous nuclear ribonucleoprotein A0 (hnRNP A0) mRNA-binding component of ribonucleosomes. Specifically binds AU-rich element (ARE)-containing mRNAs. Involved in post-transcriptional regulation of cytokines mRNAs. {ECO:0000269|PubMed:12456657}.
Q13263 TRIM28 S41 ochoa Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
Q13263 TRIM28 S43 ochoa Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
Q13263 TRIM28 S45 ochoa Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
Q13263 TRIM28 S49 ochoa Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
Q13263 TRIM28 S102 ochoa Transcription intermediary factor 1-beta (TIF1-beta) (E3 SUMO-protein ligase TRIM28) (EC 2.3.2.27) (KRAB-associated protein 1) (KAP-1) (KRAB-interacting protein 1) (KRIP-1) (Nuclear corepressor KAP-1) (RING finger protein 96) (RING-type E3 ubiquitin transferase TIF1-beta) (Tripartite motif-containing protein 28) Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.; FUNCTION: (Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1. {ECO:0000269|PubMed:24741090}.
Q13428 TCOF1 S328 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}.
Q13439 GOLGA4 S26 ochoa Golgin subfamily A member 4 (256 kDa golgin) (Golgin-245) (Protein 72.1) (Trans-Golgi p230) Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking (PubMed:29084197). {ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:29084197}.
Q13459 MYO9B S1323 ochoa Unconventional myosin-IXb (Unconventional myosin-9b) Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}.
Q13563 PKD2 S74 ochoa Polycystin-2 (PC2) (Autosomal dominant polycystic kidney disease type II protein) (Polycystic kidney disease 2 protein) (Polycystwin) (R48321) (Transient receptor potential cation channel subfamily P member 2) Forms a nonselective cation channel (PubMed:11854751, PubMed:11991947, PubMed:15692563, PubMed:26269590, PubMed:27071085, PubMed:31441214, PubMed:39009345). Can function as a homotetrameric ion channel or can form heteromer with PKD1 (PubMed:31441214, PubMed:33164752). Displays distinct function depending on its subcellular localization and regulation by its binding partners (PubMed:11854751, PubMed:11991947, PubMed:27214281, PubMed:29899465). In primary cilium functions as a cation channel, with a preference for monovalent cations over divalent cations that allows K(+), Na(+) and Ca(2+) influx, with low selectivity for Ca(2+) (PubMed:27071085). Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). In the endoplasmic reticulum, likely functions as a K(+) channel to facilitate Ca(2+) release (By similarity). The heterotetrameric PKD1/PKD2 channel has higher Ca(2+) permeability than homomeric PKD2 channel and acts as a primarily Ca(2+)-permeable channel (PubMed:31441214). Interacts with and acts as a regulator of a number of other channels, such as TRPV4, TRPC1, IP3R, RYR2, ultimately further affecting intracellular signaling, to modulate intracellular Ca(2+) signaling (PubMed:11854751, PubMed:11991947, PubMed:27214281, PubMed:29899465). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). In cardiomyocytes, PKD2 modulates Ca(2+) release from stimulated RYR2 receptors through direct association (By similarity). Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning (By similarity). Acts as a regulator of cilium length together with PKD1 (By similarity). Mediates systemic blood pressure and contributes to the myogenic response in cerebral arteries though vasoconstriction (By similarity). {ECO:0000250|UniProtKB:O35245, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:11991947, ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:26269590, ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:31441214, ECO:0000269|PubMed:33164752, ECO:0000269|PubMed:39009345}.
Q14151 SAFB2 S324 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.
Q14244 MAP7 S247 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}.
Q14764 MVP S585 ochoa Major vault protein (MVP) (Lung resistance-related protein) Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases. {ECO:0000269|PubMed:15133037, ECO:0000269|PubMed:16418217, ECO:0000269|PubMed:16441665}.
Q14938 NFIX S239 ochoa Nuclear factor 1 X-type (NF1-X) (Nuclear factor 1/X) (CCAAT-box-binding transcription factor) (CTF) (Nuclear factor I/X) (NF-I/X) (NFI-X) (TGGCA-binding protein) Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.
Q15084 PDIA6 S129 ochoa Protein disulfide-isomerase A6 (EC 5.3.4.1) (Endoplasmic reticulum protein 5) (ER protein 5) (ERp5) (Protein disulfide isomerase P5) (Thioredoxin domain-containing protein 7) May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936). {ECO:0000269|PubMed:12204115, ECO:0000269|PubMed:15466936, ECO:0000269|PubMed:24508390}.
Q15334 LLGL1 S682 ochoa Lethal(2) giant larvae protein homolog 1 (LLGL) (DLG4) (Hugl-1) (Human homolog to the D-lgl gene protein) Cortical cytoskeleton protein found in a complex involved in maintaining cell polarity and epithelial integrity. Involved in the regulation of mitotic spindle orientation, proliferation, differentiation and tissue organization of neuroepithelial cells. Involved in axonogenesis through RAB10 activation thereby regulating vesicular membrane trafficking toward the axonal plasma membrane. {ECO:0000269|PubMed:15735678, ECO:0000269|PubMed:16170365}.
Q15424 SAFB S20 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}.
Q15424 SAFB S325 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}.
Q16512 PKN1 S301 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}.
Q16637 SMN1 S49 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}.
Q24JP5 TMEM132A S529 ochoa Transmembrane protein 132A (HSPA5-binding protein 1) May play a role in embryonic and postnatal development of the brain. Increased resistance to cell death induced by serum starvation in cultured cells. Regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation (By similarity). {ECO:0000250}.
Q2KJY2 KIF26B S972 ochoa Kinesin-like protein KIF26B Essential for embryonic kidney development. Plays an important role in the compact adhesion between mesenchymal cells adjacent to the ureteric buds, possibly by interacting with MYH10. This could lead to the establishment of the basolateral integrity of the mesenchyme and the polarized expression of ITGA8, which maintains the GDNF expression required for further ureteric bud attraction. Although it seems to lack ATPase activity it is constitutively associated with microtubules (By similarity). {ECO:0000250}.
Q2M1K9 ZNF423 S1054 ochoa Zinc finger protein 423 (Olf1/EBF-associated zinc finger protein) (hOAZ) (Smad- and Olf-interacting zinc finger protein) Transcription factor that can both act as an activator or a repressor depending on the context. Plays a central role in BMP signaling and olfactory neurogenesis. 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 in terminal olfactory receptor neurons differentiation; this interaction preventing EBF1 to bind DNA and activate olfactory-specific genes. Involved in olfactory neurogenesis by participating in a developmental switch that regulates the transition from differentiation to maturation in olfactory receptor neurons. Controls proliferation and differentiation of neural precursors in cerebellar vermis formation. {ECO:0000269|PubMed:10660046}.
Q3B7T1 EDRF1 S1144 ochoa Erythroid differentiation-related factor 1 Transcription factor involved in erythroid differentiation. Involved in transcriptional activation of the globin gene. {ECO:0000269|PubMed:12609092}.
Q3KRA9 ALKBH6 S197 ochoa Probable RNA/DNA demethylase ALKBH6 (EC 1.14.11.-) (Alkylated DNA repair protein alkB homolog 6) (Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6) (Probable nucleic acid dioxygenase ALKBH6) Probable Fe(2+)/2-oxoglutarate-dependent dioxygenase involved in oxidative demethylation of nucleic acids (PubMed:39845104). Binds nucleic acids with a preference for ssDNA or ssRNA to other types of DNAs (PubMed:35120926). May play a role in nucleic acid damage repair (PubMed:35120926). {ECO:0000269|PubMed:35120926, ECO:0000269|PubMed:39845104}.
Q53H80 AKIRIN2 S39 ochoa Akirin-2 Molecular adapter that acts as a bridge between a variety of multiprotein complexes, and which is involved in embryonic development, immunity, myogenesis and brain development (PubMed:34711951). Plays a key role in nuclear protein degradation by promoting import of proteasomes into the nucleus: directly binds to fully assembled 20S proteasomes at one end and to nuclear import receptor IPO9 at the other end, bridging them together and mediating the import of pre-assembled proteasome complexes through the nuclear pore (PubMed:34711951). Involved in innate immunity by regulating the production of interleukin-6 (IL6) downstream of Toll-like receptor (TLR): acts by bridging the NF-kappa-B inhibitor NFKBIZ and the SWI/SNF complex, leading to promote induction of IL6 (By similarity). Also involved in adaptive immunity by promoting B-cell activation (By similarity). Involved in brain development: required for the survival and proliferation of cerebral cortical progenitor cells (By similarity). Involved in myogenesis: required for skeletal muscle formation and skeletal development, possibly by regulating expression of muscle differentiation factors (By similarity). Also plays a role in facilitating interdigital tissue regression during limb development (By similarity). {ECO:0000250|UniProtKB:B1AXD8, ECO:0000269|PubMed:34711951}.
Q562E7 WDR81 S698 ochoa WD repeat-containing protein 81 Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (PubMed:28404643). May also be involved in maintenance of normal mitochondrial structure and organization (By similarity). {ECO:0000250|UniProtKB:Q5ND34, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989, ECO:0000269|PubMed:28404643}.
Q5BJH7 YIF1B S65 ochoa Protein YIF1B (YIP1-interacting factor homolog B) Functions in endoplasmic reticulum to Golgi vesicle-mediated transport and regulates the proper organization of the endoplasmic reticulum and the Golgi (By similarity). Plays a key role in targeting to neuronal dendrites receptors such as HTR1A (By similarity). Plays also a role in primary cilium and sperm flagellum assembly probably through protein transport to these compartments (PubMed:33103737). {ECO:0000250|UniProtKB:Q6PEC3, ECO:0000250|UniProtKB:Q9CX30, ECO:0000269|PubMed:33103737}.
Q5FWE3 PRRT3 S900 ochoa Proline-rich transmembrane protein 3 None
Q5VZ89 DENND4C S1382 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}.
Q5XUX0 FBXO31 S33 ochoa|psp F-box only protein 31 Substrate-recognition component of the SCF(FBXO31) protein ligase complex, which specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress, leading to their degradation by the proteasome (PubMed:39880951). FBXO31 specifically recognizes and binds C-terminal peptides bearing an amide: C-terminal amidation in response to oxidative stress takes place following protein fragmentation (PubMed:39880951). The SCF(FBXO31) also plays a role in G1 arrest following DNA damage by mediating ubiquitination of phosphorylated cyclin-D1 (CCND1), promoting its degradation by the proteasome, resulting in G1 arrest (PubMed:19412162, PubMed:29279382). The SCF(FBXO31) complex is however not a major regulator of CCND1 stability during the G1/S transition (By similarity). In response to genotoxic stress, the SCF(FBXO31) complex directs ubiquitination and degradation of phosphorylated MDM2, thereby promoting p53/TP53-mediated DNA damage response (PubMed:26124108). SCF(FBXO31) complex is required for genomic integrity by catalyzing ubiquitination and degradation of cyclin-A (CCNA1 and/or CCNA2) during the G1 phase (PubMed:31413110). In response to genotoxic stress, the SCF(FBXO31) complex directs ubiquitination and degradation of phosphorylated FBXO46 and MAP2K6 (PubMed:24936062, PubMed:30171069). SCF(FBXO31) complex promotes ubiquitination and degradation of CDT1 during the G2 phase to prevent re-replication (PubMed:24828503). The SCF(FBXO31) complex also mediates ubiquitination and degradation of DUSP6, OGT and PARD6A (PubMed:23469015, PubMed:34686346, PubMed:39894887). {ECO:0000250|UniProtKB:Q3TQF0, ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:23469015, ECO:0000269|PubMed:24828503, ECO:0000269|PubMed:24936062, ECO:0000269|PubMed:26124108, ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:31413110, ECO:0000269|PubMed:34686346, ECO:0000269|PubMed:39880951, ECO:0000269|PubMed:39894887}.
Q641Q2 WASHC2A S498 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}.
Q66K74 MAP1S S759 ochoa Microtubule-associated protein 1S (MAP-1S) (BPY2-interacting protein 1) (Microtubule-associated protein 8) (Variable charge Y chromosome 2-interacting protein 1) (VCY2-interacting protein 1) (VCY2IP-1) [Cleaved into: MAP1S heavy chain; MAP1S light chain] Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles (By similarity). {ECO:0000250, ECO:0000269|PubMed:15899810, ECO:0000269|PubMed:17234756}.
Q6P1M0 SLC27A4 S555 ochoa Long-chain fatty acid transport protein 4 (FATP-4) (Fatty acid transport protein 4) (Arachidonate--CoA ligase) (EC 6.2.1.15) (Long-chain-fatty-acid--CoA ligase) (EC 6.2.1.3) (Solute carrier family 27 member 4) (Very long-chain acyl-CoA synthetase 4) (ACSVL4) (EC 6.2.1.-) Mediates the levels of long-chain fatty acids (LCFA) in the cell by facilitating their transport across cell membranes (PubMed:10518211, PubMed:12556534, PubMed:20448275, PubMed:21395585, PubMed:22022213). Appears to be the principal fatty acid transporter in small intestinal enterocytes (PubMed:20448275). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (PubMed:22022213, PubMed:24269233). Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis (By similarity). Probably involved in fatty acid transport across the blood barrier (PubMed:21395585). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones (By similarity). {ECO:0000250|UniProtKB:Q91VE0, ECO:0000269|PubMed:10518211, ECO:0000269|PubMed:12556534, ECO:0000269|PubMed:20448275, ECO:0000269|PubMed:21395585, ECO:0000269|PubMed:22022213, ECO:0000269|PubMed:24269233}.
Q6P1R3 MSANTD2 S63 ochoa Myb/SANT-like DNA-binding domain-containing protein 2 None
Q6P3S6 FBXO42 S545 ochoa F-box only protein 42 (Just one F-box and Kelch domain-containing protein) Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Specifically recognizes p53/TP53, promoting its ubiquitination and degradation. {ECO:0000269|PubMed:19509332}.
Q6PL24 TMED8 S39 ochoa Protein TMED8 None
Q6SPF0 SAMD1 S23 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}.
Q6W2J9 BCOR S571 ochoa BCL-6 corepressor (BCoR) Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as BCL6 and MLLT3. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor. Involved in the repression of TFAP2A; impairs binding of BCL6 and KDM2B to TFAP2A promoter regions. Via repression of TFAP2A acts as a negative regulator of osteo-dentiogenic capacity in adult stem cells; the function implies inhibition of methylation on histone H3 'Lys-4' (H3K4me3) and 'Lys-36' (H3K36me2). {ECO:0000269|PubMed:10898795, ECO:0000269|PubMed:15004558, ECO:0000269|PubMed:18280243, ECO:0000269|PubMed:19578371, ECO:0000269|PubMed:23911289}.
Q6ZN55 ZNF574 S717 ochoa Zinc finger protein 574 May be involved in transcriptional regulation.
Q6ZNB6 NFXL1 S62 ochoa NF-X1-type zinc finger protein NFXL1 (Ovarian zinc finger protein) (hOZFP) None
Q6ZRI6 C15orf39 S586 ochoa Uncharacterized protein C15orf39 None
Q6ZRV2 FAM83H S759 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}.
Q6ZU67 BEND4 S98 ochoa BEN domain-containing protein 4 (Coiled-coil domain-containing protein 4) None
Q6ZUT6 CCDC9B S387 ochoa Coiled-coil domain-containing protein 9B None
Q6ZW13 C16orf86 S172 ochoa Uncharacterized protein C16orf86 None
Q71RC2 LARP4 S673 ochoa La-related protein 4 (La ribonucleoprotein domain family member 4) RNA binding protein that binds to the poly-A tract of mRNA molecules (PubMed:21098120). Associates with the 40S ribosomal subunit and with polysomes (PubMed:21098120). Plays a role in the regulation of mRNA translation (PubMed:21098120). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987, PubMed:27615744). {ECO:0000269|PubMed:21098120, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:27615744}.
Q7L311 ARMCX2 S213 ochoa Armadillo repeat-containing X-linked protein 2 (ARM protein lost in epithelial cancers on chromosome X 2) (Protein ALEX2) May regulate the dynamics and distribution of mitochondria in neural cells. {ECO:0000250|UniProtKB:Q6A058}.
Q7LFL8 CXXC5 S48 ochoa CXXC-type zinc finger protein 5 (CF5) (Putative MAPK-activating protein PM08) (Putative NF-kappa-B-activating protein 102) (Retinoid-inducible nuclear factor) (RINF) May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q5XIQ3, ECO:0000269|PubMed:19182210, ECO:0000269|PubMed:19557330, ECO:0000269|PubMed:23303788, ECO:0000269|PubMed:29276034}.
Q7RTV3 ZNF367 S123 ochoa Zinc finger protein 367 (C2H2 zinc finger protein ZFF29) Transcriptional activator. Isoform 1 may be involved in transcriptional activation of erythroid genes. {ECO:0000269|PubMed:15344908}.
Q7Z2Y5 NRK S1034 ochoa Nik-related protein kinase (EC 2.7.11.1) May phosphorylate cofilin-1 and induce actin polymerization through this process, during the late stages of embryogenesis. Involved in the TNF-alpha-induced signaling pathway (By similarity). {ECO:0000250}.
Q7Z460 CLASP1 S1223 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}.
Q7Z5L9 IRF2BP2 S212 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}.
Q7Z7K6 CENPV S30 ochoa Centromere protein V (CENP-V) (Nuclear protein p30) (Proline-rich protein 6) Required for distribution of pericentromeric heterochromatin in interphase nuclei and for centromere formation and organization, chromosome alignment and cytokinesis. {ECO:0000269|PubMed:18772885}.
Q86U90 YRDC S60 ochoa Threonylcarbamoyl-AMP synthase (EC 2.7.7.87) (Dopamine receptor-interacting protein 3) (Ischemia/reperfusion-inducible protein homolog) (hIRIP) Cytoplasmic and mitochondrial threonylcarbamoyl-AMP synthase required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine (PubMed:29760464, PubMed:31481669, PubMed:34545459). Catalyzes the conversion of L-threonine, HCO(3)(-)/CO(2) and ATP to give threonylcarbamoyl-AMP (TC-AMP) as the acyladenylate intermediate, with the release of diphosphate (PubMed:29760464). Participates in t(6)A37 formation in cytoplasmic and mitochondrial tRNAs (PubMed:29760464). May regulate the activity of some transporters (By similarity). {ECO:0000250|UniProtKB:Q3U5F4, ECO:0000269|PubMed:29760464, ECO:0000269|PubMed:31481669, ECO:0000269|PubMed:34545459}.
Q86XP1 DGKH S691 ochoa Diacylglycerol kinase eta (DAG kinase eta) (EC 2.7.1.107) (Diglyceride kinase eta) (DGK-eta) Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:12810723, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable) (PubMed:12810723, PubMed:23949095). Plays a key role in promoting cell growth (PubMed:19710016). Activates the Ras/B-Raf/C-Raf/MEK/ERK signaling pathway induced by EGF (PubMed:19710016). Regulates the recruitment of RAF1 and BRAF from cytoplasm to membranes and their heterodimerization (PubMed:19710016). {ECO:0000269|PubMed:12810723, ECO:0000269|PubMed:19710016, ECO:0000269|PubMed:23949095, ECO:0000305}.
Q8IUW3 SPATA2L S332 ochoa Spermatogenesis-associated protein 2-like protein (SPATA2-like protein) None
Q8IY33 MICALL2 S247 ochoa MICAL-like protein 2 (Junctional Rab13-binding protein) (Molecule interacting with CasL-like 2) (MICAL-L2) Effector of small Rab GTPases which is involved in junctional complexes assembly through the regulation of cell adhesion molecules transport to the plasma membrane and actin cytoskeleton reorganization. Regulates the endocytic recycling of occludins, claudins and E-cadherin to the plasma membrane and may thereby regulate the establishment of tight junctions and adherens junctions. In parallel, may regulate actin cytoskeleton reorganization directly through interaction with F-actin or indirectly through actinins and filamins. Most probably involved in the processes of epithelial cell differentiation, cell spreading and neurite outgrowth (By similarity). Undergoes liquid-liquid phase separation to form tubular recycling endosomes. Plays 2 sequential roles in the biogenesis of tubular recycling endosomes: first organizes phase separation and then the closed form formed by interaction with RAB8A promotes endosomal tubulation (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q3TN34}.
Q8IY33 MICALL2 S249 ochoa MICAL-like protein 2 (Junctional Rab13-binding protein) (Molecule interacting with CasL-like 2) (MICAL-L2) Effector of small Rab GTPases which is involved in junctional complexes assembly through the regulation of cell adhesion molecules transport to the plasma membrane and actin cytoskeleton reorganization. Regulates the endocytic recycling of occludins, claudins and E-cadherin to the plasma membrane and may thereby regulate the establishment of tight junctions and adherens junctions. In parallel, may regulate actin cytoskeleton reorganization directly through interaction with F-actin or indirectly through actinins and filamins. Most probably involved in the processes of epithelial cell differentiation, cell spreading and neurite outgrowth (By similarity). Undergoes liquid-liquid phase separation to form tubular recycling endosomes. Plays 2 sequential roles in the biogenesis of tubular recycling endosomes: first organizes phase separation and then the closed form formed by interaction with RAB8A promotes endosomal tubulation (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q3TN34}.
Q8N2M8 CLASRP S349 ochoa CLK4-associating serine/arginine rich protein (Splicing factor, arginine/serine-rich 16) (Suppressor of white-apricot homolog 2) Probably functions as an alternative splicing regulator. May regulate the mRNA splicing of genes such as CLK1. May act by regulating members of the CLK kinase family (By similarity). {ECO:0000250}.
Q8N5W9 RFLNB S71 ochoa Refilin-B (Regulator of filamin protein B) (RefilinB) Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in the formation of cartilaginous skeletal elements. {ECO:0000250|UniProtKB:Q5SVD0}.
Q8N7S6 ARIH2OS S56 ochoa Uncharacterized protein ARIH2OS (Ariadne-2 homolog opposite strand protein) None
Q8N9B5 JMY S713 ochoa Junction-mediating and -regulatory protein Acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions (PubMed:30420355). In nucleus, acts as a cofactor that increases p53/TP53 response via its interaction with p300/EP300. Increases p53/TP53-dependent transcription and apoptosis, suggesting an important role in p53/TP53 stress response such as DNA damage. In cytoplasm, acts as a nucleation-promoting factor for both branched and unbranched actin filaments (PubMed:30420355). Activates the Arp2/3 complex to induce branched actin filament networks. Also catalyzes actin polymerization in the absence of Arp2/3, creating unbranched filaments (PubMed:30420355). Contributes to cell motility by controlling actin dynamics. May promote the rapid formation of a branched actin network by first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments. Upon nutrient stress, directly recruited by MAP1LC3B to the phagophore membrane surfaces to promote actin assembly during autophagy (PubMed:30420355). The p53/TP53-cofactor and actin activator activities are regulated via its subcellular location (By similarity). {ECO:0000250|UniProtKB:Q9QXM1, ECO:0000269|PubMed:30420355}.
Q8NC56 LEMD2 S82 ochoa LEM domain-containing protein 2 (hLEM2) Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis (PubMed:16339967, PubMed:17097643, PubMed:28242692, PubMed:32494070). Plays a role as transmembrane adapter for the endosomal sorting complexes required for transport (ESCRT), and is thereby involved in ESCRT-mediated NE reformation (PubMed:28242692, PubMed:32494070). Promotes ESCRT-mediated NE closure by recruiting CHMP7 and downstream ESCRT-III proteins IST1/CHMP8 and CHMP2A to the reforming NE during anaphase (PubMed:28242692). During nuclear reassembly, condenses into a liquid-like coating around microtubule spindles and coassembles with CHMP7 to form a macromolecular O-ring seal at the confluence between membranes, chromatin, and the spindle to facilitate early nuclear sealing (PubMed:32494070). Plays a role in the organization of heterochromatin associated with the NE and in the maintenance of NE organization under mechanical stress (By similarity). Required for embryonic development and involved in regulation of several signaling pathways such as MAPK and AKT (By similarity). Required for myoblast differentiation involving regulation of ERK signaling (By similarity). Essential for cardiac homeostasis and proper heart function (By similarity). {ECO:0000250|UniProtKB:Q6DVA0, ECO:0000269|PubMed:16339967, ECO:0000269|PubMed:17097643, ECO:0000269|PubMed:28242692, ECO:0000269|PubMed:32494070}.
Q8NFT8 DNER S696 ochoa Delta and Notch-like epidermal growth factor-related receptor Activator of the NOTCH1 pathway. May mediate neuron-glia interaction during astrocytogenesis (By similarity). {ECO:0000250}.
Q8NHG8 ZNRF2 S99 ochoa E3 ubiquitin-protein ligase ZNRF2 (EC 2.3.2.27) (Protein Ells2) (RING finger protein 202) (RING-type E3 ubiquitin transferase ZNRF2) (Zinc/RING finger protein 2) E3 ubiquitin-protein ligase that plays a role in the establishment and maintenance of neuronal transmission and plasticity. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation (PubMed:22797923). Acts also as a positive regulator of mTORC1 activation by amino acids, which functions upstream of the V-ATPase and of Rag-GTPases (PubMed:27244671). In turn, phosphorylation by mTOR leads to its inhibition via targeting to the cytosol allowing a self-regulating feedback mechanism (PubMed:27244671). {ECO:0000269|PubMed:14561866, ECO:0000269|PubMed:22797923, ECO:0000269|PubMed:27244671}.
Q8NHV4 NEDD1 S332 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}.
Q8TF01 PNISR S381 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
Q8WVB6 CHTF18 S64 ochoa Chromosome transmission fidelity protein 18 homolog (hCTF18) (CHL12) Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated by the presence of primed DNA, replication protein A (RPA) and by proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. Interacts with and stimulates DNA polymerase POLH. During DNA repair synthesis, involved in loading DNA polymerase POLE at the sites of local damage (PubMed:20227374). {ECO:0000269|PubMed:12766176, ECO:0000269|PubMed:12930902, ECO:0000269|PubMed:17545166, ECO:0000269|PubMed:20227374}.
Q8WWM7 ATXN2L S56 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}.
Q92547 TOPBP1 S805 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}.
Q92560 BAP1 S305 ochoa Ubiquitin carboxyl-terminal hydrolase BAP1 (EC 3.4.19.12) (BRCA1-associated protein 1) (Cerebral protein 6) Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1 (PubMed:12485996, PubMed:18757409, PubMed:20436459, PubMed:25451922, PubMed:35051358). Catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-120' (H2AK119ub1) (PubMed:20436459, PubMed:25451922, PubMed:30664650, PubMed:35051358). Does not deubiquitinate monoubiquitinated histone H2B (PubMed:20436459, PubMed:30664650). 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:20805357, PubMed:30664650, PubMed:36180891). Antagonizes PRC1 mediated H2AK119ub1 monoubiquitination (PubMed:30664650). As part of the PR-DUB complex, associates with chromatin enriched in histone marks H3K4me1, H3K4me3, and H3K27Ac, but not in H3K27me3 (PubMed:36180891). Recruited to specific gene-regulatory regions by YY1 (PubMed:20805357). Acts as a regulator of cell growth by mediating deubiquitination of HCFC1 N-terminal and C-terminal chains, with some specificity toward 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains (PubMed:19188440, PubMed:19815555). Deubiquitination of HCFC1 does not lead to increase stability of HCFC1 (PubMed:19188440, PubMed:19815555). Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination (PubMed:19117993). It however does not mediate deubiquitination of BRCA1 and BARD1 (PubMed:19117993). Able to mediate autodeubiquitination via intramolecular interactions to counteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration (PubMed:24703950). Negatively regulates epithelial-mesenchymal transition (EMT) of trophoblast stem cells during placental development by regulating genes involved in epithelial cell integrity, cell adhesion and cytoskeletal organization (PubMed:34170818). {ECO:0000269|PubMed:12485996, ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19117993, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:20436459, ECO:0000269|PubMed:20805357, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:34170818, ECO:0000269|PubMed:35051358, ECO:0000269|PubMed:36180891}.
Q92618 ZNF516 S116 ochoa Zinc finger protein 516 Transcriptional regulator that binds to the promoter and activates the transcription of genes promoting brown adipose tissue (BAT) differentiation. Among brown adipose tissue-specific genes, binds the proximal region of the promoter of the UCP1 gene to activate its transcription and thereby regulate thermogenesis (By similarity). May also play a role in the cellular response to replication stress (PubMed:23446422). {ECO:0000250|UniProtKB:Q7TSH3, ECO:0000269|PubMed:23446422}.
Q92619 ARHGAP45 S592 ochoa Rho GTPase-activating protein 45 [Cleaved into: Minor histocompatibility antigen HA-1 (mHag HA-1)] Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity. {ECO:0000269|PubMed:24086303}.; FUNCTION: Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL. {ECO:0000269|PubMed:12601144, ECO:0000269|PubMed:8260714, ECO:0000269|PubMed:8532022, ECO:0000269|PubMed:9798702}.
Q92766 RREB1 S1388 ochoa Ras-responsive element-binding protein 1 (RREB-1) (Finger protein in nuclear bodies) (Raf-responsive zinc finger protein LZ321) (Zinc finger motif enhancer-binding protein 1) (Zep-1) Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters (PubMed:10390538, PubMed:15067362, PubMed:17550981, PubMed:8816445, PubMed:9305772). Represses the angiotensinogen gene (PubMed:15067362). Negatively regulates the transcriptional activity of AR (PubMed:17550981). Potentiates the transcriptional activity of NEUROD1 (PubMed:12482979). Promotes brown adipocyte differentiation (By similarity). May be involved in Ras/Raf-mediated cell differentiation by enhancing calcitonin expression (PubMed:8816445). {ECO:0000250|UniProtKB:Q3UH06, ECO:0000269|PubMed:10390538, ECO:0000269|PubMed:12482979, ECO:0000269|PubMed:15067362, ECO:0000269|PubMed:17550981, ECO:0000269|PubMed:8816445, ECO:0000269|PubMed:9305772}.
Q92783 STAM S156 ochoa Signal transducing adapter molecule 1 (STAM-1) Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.; FUNCTION: (Microbial infection) Plays an important role in Dengue virus entry. {ECO:0000269|PubMed:29742433}.
Q92997 DVL3 S421 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}.
Q969F2 NKD2 S31 psp Protein naked cuticle homolog 2 (Naked-2) (hNkd2) Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity (By similarity). Required for processing of TGFA and for targeting of TGFA to the basolateral membrane of polarized epithelial cells. {ECO:0000250, ECO:0000269|PubMed:15064403, ECO:0000269|PubMed:17553928}.
Q969T9 WBP2 S229 ochoa WW domain-binding protein 2 (WBP-2) Acts as a transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation (PubMed:16772533). In presence of estrogen, binds to ESR1-responsive promoters (PubMed:16772533). Synergizes with YAP1 to enhance PGR activity (PubMed:16772533). Modulates expression of post-synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR (By similarity). {ECO:0000250|UniProtKB:P97765, ECO:0000269|PubMed:16772533}.
Q96BD5 PHF21A S113 ochoa PHD finger protein 21A (BHC80a) (BRAF35-HDAC complex protein BHC80) Component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it may act as a scaffold. Inhibits KDM1A-mediated demethylation of 'Lys-4' of histone H3 in vitro, suggesting a role in demethylation regulation. {ECO:0000269|PubMed:16140033}.
Q96C12 ARMC5 S82 ochoa Armadillo repeat-containing protein 5 Substrate-recognition component of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:39504960, PubMed:39667934). The BCR(ARMC5) complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the BCR(ARMC5) complex acts by mediating ubiquitination of Pol II subunit POLR2A phosphorylated at 'Ser-5' of the C-terminal domain (CTD), leading to POLR2A degradation (PubMed:35687106, PubMed:38225631, PubMed:39504960, PubMed:39667934). The BCR(ARMC5) complex acts in parallel of the integrator complex and is specific for RNA Pol II originating from the promoter-proximal zone: it does not ubiquitinate elongation-stalled RNA Pol II (PubMed:39667934). The BCR(ARMC5) complex also acts as a regulator of fatty acid desaturation by mediating ubiquitination and degradation of SCAP-free SREBF1 and SREBF2 (PubMed:35862218). Involved in fetal development, T-cell function and adrenal gland growth homeostasis (PubMed:24283224, PubMed:28676429). Plays a role in steroidogenesis, modulates steroidogenic enzymes expression and cortisol production (PubMed:24283224, PubMed:28676429). {ECO:0000269|PubMed:24283224, ECO:0000269|PubMed:28676429, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:35862218, ECO:0000269|PubMed:38225631, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}.
Q96EY1 DNAJA3 S167 ochoa DnaJ homolog subfamily A member 3, mitochondrial (DnaJ protein Tid-1) (hTid-1) (Hepatocellular carcinoma-associated antigen 57) (Tumorous imaginal discs protein Tid56 homolog) Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix. Affect cytochrome C release from the mitochondria and caspase 3 activation, but not caspase 8 activation. Isoform 1 increases apoptosis triggered by both TNF and the DNA-damaging agent mytomycin C; in sharp contrast, isoform 2 suppresses apoptosis. Can modulate IFN-gamma-mediated transcriptional activity. Isoform 2 may play a role in neuromuscular junction development as an effector of the MUSK signaling pathway.
Q96FS4 SIPA1 S67 ochoa Signal-induced proliferation-associated protein 1 (Sipa-1) (GTPase-activating protein Spa-1) (p130 SPA-1) GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state (PubMed:9346962). Affects cell cycle progression (By similarity). {ECO:0000250|UniProtKB:P46062, ECO:0000269|PubMed:9346962}.
Q96G42 KLHDC7B S151 ochoa Kelch domain-containing protein 7B None
Q96G74 OTUD5 S442 ochoa OTU domain-containing protein 5 (EC 3.4.19.12) (Deubiquitinating enzyme A) (DUBA) Deubiquitinating enzyme that functions as a negative regulator of the innate immune system (PubMed:17991829, PubMed:22245969, PubMed:23827681, PubMed:33523931). Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:22245969). Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro) (PubMed:22245969). Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production (PubMed:17991829). Controls neuroectodermal differentiation through cleaving 'Lys-48'-linked ubiquitin chains to counteract degradation of select chromatin regulators such as ARID1A, HDAC2 and HCF1 (PubMed:33523931). Acts as a positive regulator of mTORC1 and mTORC2 signaling following phosphorylation by MTOR: acts by mediating deubiquitination of BTRC, leading to its stability (PubMed:33110214). {ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:22245969, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:33110214, ECO:0000269|PubMed:33523931}.
Q96I24 FUBP3 S532 ochoa Far upstream element-binding protein 3 (FUSE-binding protein 3) May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression.
Q96K37 SLC35E1 S19 ochoa Solute carrier family 35 member E1 Putative transporter. {ECO:0000250}.
Q96KG9 SCYL1 S568 ochoa N-terminal kinase-like protein (Coated vesicle-associated kinase of 90 kDa) (SCY1-like protein 1) (Telomerase regulation-associated protein) (Telomerase transcriptional element-interacting factor) (Teratoma-associated tyrosine kinase) Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). {ECO:0000269|PubMed:18556652, ECO:0000269|PubMed:26581903}.; FUNCTION: [Isoform 6]: Acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region. {ECO:0000269|PubMed:15963946}.
Q96QP1 ALPK1 S781 ochoa Alpha-protein kinase 1 (EC 2.7.11.1) (Chromosome 4 kinase) (Lymphocyte alpha-protein kinase) Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity (PubMed:28222186, PubMed:28877472, PubMed:30111836). Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria (PubMed:30111836). ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering pro-inflammatory NF-kappa-B signaling (PubMed:30111836). May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A (PubMed:27169898). May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A (PubMed:15883161). May play a role in ciliogenesis (PubMed:30967659). {ECO:0000269|PubMed:15883161, ECO:0000269|PubMed:27169898, ECO:0000269|PubMed:28222186, ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836, ECO:0000269|PubMed:30967659}.
Q96RY5 CRAMP1 S596 ochoa Protein cramped-like (Cramped chromatin regulator homolog 1) (Hematological and neurological expressed 1-like protein) None
Q96S55 WRNIP1 S151 ochoa ATPase WRNIP1 (EC 3.6.1.-) (Werner helicase-interacting protein 1) Functions as a modulator of initiation or reinitiation events during DNA polymerase delta-mediated DNA synthesis. In the presence of ATP, stimulation of DNA polymerase delta-mediated DNA synthesis is decreased. Also plays a role in the innate immune defense against viruses. Stabilizes the RIGI dsRNA interaction and promotes RIGI 'Lys-63'-linked polyubiquitination. In turn, RIGI transmits the signal through mitochondrial MAVS. {ECO:0000269|PubMed:15670210, ECO:0000269|PubMed:29053956}.
Q96SI9 STRBP S565 ochoa Spermatid perinuclear RNA-binding protein Involved in spermatogenesis and sperm function. Plays a role in regulation of cell growth. Binds to double-stranded DNA and RNA. Binds most efficiently to poly(I:C) RNA than to poly(dI:dC) DNA. Binds also to single-stranded poly(G) RNA. Binds non-specifically to the mRNA PRM1 3'-UTR and adenovirus VA RNA (By similarity). {ECO:0000250}.
Q96T58 SPEN S2101 ochoa Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}.
Q99536 VAT1 S44 ochoa Synaptic vesicle membrane protein VAT-1 homolog (EC 1.-.-.-) Possesses ATPase activity (By similarity). Plays a part in calcium-regulated keratinocyte activation in epidermal repair mechanisms. Has no effect on cell proliferation. Negatively regulates mitochondrial fusion in cooperation with mitofusin proteins (MFN1-2). {ECO:0000250, ECO:0000269|PubMed:12898150, ECO:0000269|PubMed:17105775, ECO:0000269|PubMed:19508442}.
Q99684 GFI1 S71 ochoa Zinc finger protein Gfi-1 (Growth factor independent protein 1) (Zinc finger protein 163) Transcription repressor essential for hematopoiesis (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Functions in a cell-context and development-specific manner (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes (PubMed:11060035, PubMed:17197705, PubMed:17646546, PubMed:18805794, PubMed:19164764, PubMed:20190815, PubMed:8754800). Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16287849). Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development (PubMed:12778173). Inhibits SPI1 transcriptional activity at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (By similarity). Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling (By similarity). Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA (PubMed:20547752). Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth (PubMed:19026687). Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters (PubMed:16287849). Required for the maintenance of inner ear hair cells (By similarity). In addition to its role in transcription, acts as a substrate adapter for PRMT1 in the DNA damage response: facilitates the recognition of TP53BP1 and MRE11 substrates by PRMT1, promoting their methylation and the DNA damage response (PubMed:29651020). {ECO:0000250|UniProtKB:P70338, ECO:0000269|PubMed:11060035, ECO:0000269|PubMed:12778173, ECO:0000269|PubMed:16287849, ECO:0000269|PubMed:17197705, ECO:0000269|PubMed:17646546, ECO:0000269|PubMed:18805794, ECO:0000269|PubMed:19026687, ECO:0000269|PubMed:19164764, ECO:0000269|PubMed:20190815, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:29651020, ECO:0000269|PubMed:8754800}.
Q99700 ATXN2 S728 ochoa Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}.
Q9BQ89 FAM110A S228 ochoa Protein FAM110A None
Q9BR76 CORO1B S431 ochoa Coronin-1B (Coronin-2) Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity). {ECO:0000250, ECO:0000269|PubMed:16027158}.
Q9BRJ6 C7orf50 S36 ochoa Protein cholesin Hormone secreted from the intestine in response to cholesterol, where it acts to inhibit cholesterol synthesis in the liver and VLDL secretion,leading to a reduction in circulating cholesterol levels. Acts through binding to its receptor, GPR146. {ECO:0000269|PubMed:38503280}.
Q9BTC0 DIDO1 S111 ochoa Death-inducer obliterator 1 (DIO-1) (hDido1) (Death-associated transcription factor 1) (DATF-1) Putative transcription factor, weakly pro-apoptotic when overexpressed (By similarity). Tumor suppressor. Required for early embryonic stem cell development. {ECO:0000250, ECO:0000269|PubMed:16127461}.; FUNCTION: [Isoform 2]: Displaces isoform 4 at the onset of differentiation, required for repression of stemness genes. {ECO:0000269|PubMed:16127461}.
Q9BWH6 RPAP1 S301 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}.
Q9BYB0 SHANK3 S366 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}.
Q9BZK7 TBL1XR1 S119 ochoa F-box-like/WD repeat-containing protein TBL1XR1 (Nuclear receptor corepressor/HDAC3 complex subunit TBLR1) (TBL1-related protein 1) (Transducin beta-like 1X-related protein 1) F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation. {ECO:0000269|PubMed:14980219}.
Q9C0C2 TNKS1BP1 S899 ochoa 182 kDa tankyrase-1-binding protein None
Q9C0K0 BCL11B S159 ochoa B-cell lymphoma/leukemia 11B (BCL-11B) (B-cell CLL/lymphoma 11B) (COUP-TF-interacting protein 2) (Radiation-induced tumor suppressor gene 1 protein) (hRit1) Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC-rich response element (By similarity). May also function in the P53-signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q99PV8, ECO:0000269|PubMed:16809611, ECO:0000269|PubMed:27959755}.
Q9GZT9 EGLN1 S125 ochoa|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}.
Q9H4Z2 ZNF335 S1016 ochoa Zinc finger protein 335 (NRC-interacting factor 1) (NIF-1) Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters (PubMed:19131338, PubMed:23178126). Enhances ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:12215545, PubMed:18180299, PubMed:19131338). Plays an important role in neural progenitor cell proliferation and self-renewal through the regulation of specific genes involved brain development, including REST (PubMed:23178126). Also controls the expression of genes involved in somatic development and regulates, for instance, lymphoblast proliferation (PubMed:23178126). {ECO:0000269|PubMed:12215545, ECO:0000269|PubMed:18180299, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:23178126}.
Q9HCM7 FBRSL1 S844 ochoa Fibrosin-1-like protein (AUTS2-like protein) (HBV X-transactivated gene 9 protein) (HBV XAg-transactivated protein 9) None
Q9HDC5 JPH1 S185 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.
Q9NP31 SH2D2A S43 ochoa SH2 domain-containing protein 2A (SH2 domain-containing adapter protein) (T cell-specific adapter protein) (TSAd) (VEGF receptor-associated protein) Could be a T-cell-specific adapter protein involved in the control of T-cell activation. May play a role in the CD4-p56-LCK-dependent signal transduction pathway. Could also play an important role in normal and pathological angiogenesis. Could be an adapter protein that facilitates and regulates interaction of KDR with effector proteins important to endothelial cell survival and proliferation.
Q9NQT8 KIF13B S1689 ochoa Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes. {ECO:0000269|PubMed:20194617}.
Q9NQX7 ITM2C S30 ochoa Integral membrane protein 2C (Cerebral protein 14) (Transmembrane protein BRI3) [Cleaved into: CT-BRI3] Negative regulator of amyloid-beta peptide production. May inhibit the processing of APP by blocking its access to alpha- and beta-secretase. Binding to the beta-secretase-cleaved APP C-terminal fragment is negligible, suggesting that ITM2C is a poor gamma-secretase cleavage inhibitor. May play a role in TNF-induced cell death and neuronal differentiation (By similarity). {ECO:0000250, ECO:0000269|PubMed:18452648, ECO:0000269|PubMed:19366692}.
Q9NR33 POLE4 S25 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}.
Q9NWM3 CUEDC1 S351 ochoa CUE domain-containing protein 1 None
Q9NWV8 BABAM1 S57 ochoa BRISC and BRCA1-A complex member 1 (Mediator of RAP80 interactions and targeting subunit of 40 kDa) (New component of the BRCA1-A complex) Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). {ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749}.
Q9NYJ8 TAB2 S419 psp TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Mitogen-activated protein kinase kinase kinase 7-interacting protein 2) (TAK1-binding protein 2) (TAB-2) (TGF-beta-activated kinase 1-binding protein 2) Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122, PubMed:27746020, PubMed:33184450, PubMed:36681779). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:10882101, PubMed:11460167, PubMed:15327770, PubMed:22158122, PubMed:27746020). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:18079694, PubMed:22158122). Also recognizes and binds Lys-63'-linked polyubiquitin chains of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains (PubMed:27746020). Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (By similarity). Involved in heart development (PubMed:20493459). {ECO:0000250|UniProtKB:Q99K90, ECO:0000269|PubMed:10882101, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:15327770, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:20493459, ECO:0000269|PubMed:22158122, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:33184450, ECO:0000269|PubMed:36681779}.
Q9NYP3 DONSON S34 ochoa Protein downstream neighbor of Son (B17) Replisome component that maintains genome stability by protecting stalled or damaged replication forks. After the induction of replication stress, required for the stabilization of stalled replication forks, the efficient activation of the intra-S-phase and G/2M cell-cycle checkpoints and the maintenance of genome stability. {ECO:0000269|PubMed:28191891}.
Q9NZ56 FMN2 S317 ochoa Formin-2 Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:21730168, PubMed:22330775). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:21730168, PubMed:22330775). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis (By similarity). Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest (PubMed:23375502). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). Protects cells against apoptosis by protecting CDKN1A against degradation (PubMed:23375502). {ECO:0000250|UniProtKB:Q9JL04, ECO:0000269|PubMed:21730168, ECO:0000269|PubMed:22330775, ECO:0000269|PubMed:23375502, ECO:0000269|PubMed:26287480}.
Q9NZ56 FMN2 S461 ochoa Formin-2 Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:21730168, PubMed:22330775). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:21730168, PubMed:22330775). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis (By similarity). Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest (PubMed:23375502). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). Protects cells against apoptosis by protecting CDKN1A against degradation (PubMed:23375502). {ECO:0000250|UniProtKB:Q9JL04, ECO:0000269|PubMed:21730168, ECO:0000269|PubMed:22330775, ECO:0000269|PubMed:23375502, ECO:0000269|PubMed:26287480}.
Q9NZT2 OGFR S473 ochoa Opioid growth factor receptor (OGFr) (Protein 7-60) (Zeta-type opioid receptor) Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation.
Q9P1Z0 ZBTB4 S715 ochoa Zinc finger and BTB domain-containing protein 4 (KAISO-like zinc finger protein 1) (KAISO-L1) Transcriptional repressor with bimodal DNA-binding specificity. Represses transcription in a methyl-CpG-dependent manner. Binds with a higher affinity to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' but can also bind to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Can also bind specifically to a single methyl-CpG pair and can bind hemimethylated DNA but with a lower affinity compared to methylated DNA (PubMed:16354688). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (By similarity). {ECO:0000250|UniProtKB:Q5F293, ECO:0000269|PubMed:16354688}.
Q9P253 VPS18 S689 ochoa Vacuolar protein sorting-associated protein 18 homolog (hVPS18) Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in dendrite development of Pukinje cells (By similarity). {ECO:0000250|UniProtKB:Q8R307, ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25783203}.
Q9UBS8 RNF14 S162 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}.
Q9UBW8 COPS7A S232 ochoa|psp COP9 signalosome complex subunit 7a (SGN7a) (Signalosome subunit 7a) (Dermal papilla-derived protein 10) (JAB1-containing signalosome subunit 7a) Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:9535219}.
Q9UFD9 RIMBP3 S1228 ochoa RIMS-binding protein 3A (RIM-BP3.A) (RIMS-binding protein 3.1) (RIM-BP3.1) Probable component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development. {ECO:0000250|UniProtKB:Q3V0F0}.
Q9UIF9 BAZ2A S1163 ochoa Bromodomain adjacent to zinc finger domain protein 2A (Transcription termination factor I-interacting protein 5) (TTF-I-interacting protein 5) (Tip5) (hWALp3) Regulatory subunit of the ATP-dependent NoRC-1 and NoRC-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: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). Directly stimulates the ATPase activity of SMARCA5 in the NoRC-5 ISWI chromatin remodeling complex (PubMed:28801535). The NoRC-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NoRC-5 ISWI chromatin remodeling complex (PubMed:28801535). Within the NoRC-5 ISWI chromatin remodeling complex, mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity). In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription (By similarity). Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac (By similarity). Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity). {ECO:0000250|UniProtKB:Q91YE5, ECO:0000269|PubMed:28801535}.
Q9UJW0 DCTN4 S196 ochoa Dynactin subunit 4 (Dyn4) (Dynactin subunit p62) Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. {ECO:0000250|UniProtKB:A0A4X1TB62}.
Q9UKY7 CDV3 S30 ochoa Protein CDV3 homolog None
Q9ULJ3 ZBTB21 S458 ochoa Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}.
Q9UQ35 SRRM2 S2236 ochoa Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}.
Q9UQ35 SRRM2 S2365 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}.
Q9UQB8 BAIAP2 S475 ochoa BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}.
Q9UQB8 BAIAP2 S484 ochoa BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}.
Q9Y237 PIN4 S19 psp Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (EC 5.2.1.8) (Parvulin-14) (Par14) (hPar14) (Parvulin-17) (Par17) (hPar17) (Peptidyl-prolyl cis-trans isomerase Pin4) (PPIase Pin4) (Peptidyl-prolyl cis/trans isomerase EPVH) (hEPVH) (Rotamase Pin4) Isoform 1 is involved as a ribosomal RNA processing factor in ribosome biogenesis. Binds to tightly bent AT-rich stretches of double-stranded DNA. {ECO:0000269|PubMed:19369196}.; FUNCTION: Isoform 2 binds to double-stranded DNA. {ECO:0000269|PubMed:19369196}.
Q9Y2H9 MAST1 S1413 ochoa Microtubule-associated serine/threonine-protein kinase 1 (EC 2.7.11.1) (Syntrophin-associated serine/threonine-protein kinase) Microtubule-associated protein essential for correct brain development (PubMed:30449657). Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins (By similarity). {ECO:0000250|UniProtKB:Q9R1L5, ECO:0000269|PubMed:30449657}.
Q9Y2K7 KDM2A S558 ochoa Lysine-specific demethylase 2A (EC 1.14.11.27) (CXXC-type zinc finger protein 8) (F-box and leucine-rich repeat protein 11) (F-box protein FBL7) (F-box protein Lilina) (F-box/LRR-repeat protein 11) (JmjC domain-containing histone demethylation protein 1A) ([Histone-H3]-lysine-36 demethylase 1A) Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-BMAL1 heterodimer and RORA in a catalytically-independent manner (PubMed:26037310). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:19001877, ECO:0000269|PubMed:26037310, ECO:0000269|PubMed:28262558}.
Q9Y2T1 AXIN2 S493 ochoa Axin-2 (Axin-like protein) (Axil) (Axis inhibition protein 2) (Conductin) Inhibitor of the Wnt signaling pathway. Down-regulates beta-catenin. Probably facilitate the phosphorylation of beta-catenin and APC by GSK3B. {ECO:0000250|UniProtKB:O15169}.
Q9Y450 HBS1L S205 ochoa HBS1-like protein (EC 3.6.5.-) (ERFS) GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway (PubMed:21448132, PubMed:23667253, PubMed:27863242). The Pelota-HBS1L complex recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel (PubMed:27863242). Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132, PubMed:32006463). {ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:23667253, ECO:0000269|PubMed:27863242, ECO:0000269|PubMed:32006463}.
Q9Y490 TLN1 S458 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}.
Q9Y490 TLN1 S677 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}.
Q9Y4B6 DCAF1 S895 ochoa DDB1- and CUL4-associated factor 1 (HIV-1 Vpr-binding protein) (VprBP) (Serine/threonine-protein kinase VPRBP) (EC 2.7.11.1) (Vpr-interacting protein) Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2 (PubMed:23063525). Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination (By similarity). Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:19287380, PubMed:23362280). The EDVP complex also mediates ubiquitination and degradation of CCP110 (PubMed:28242748, PubMed:34259627). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription (PubMed:24140421). H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (By similarity). {ECO:0000250|UniProtKB:Q80TR8, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:18606781, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:20644714, ECO:0000269|PubMed:22184063, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:24140421, ECO:0000269|PubMed:28242748, ECO:0000269|PubMed:34259627}.; FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT. {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:17559673, ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17620334, ECO:0000269|PubMed:17626091, ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:24116224}.; FUNCTION: (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:18464893, ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:19923175, ECO:0000269|PubMed:24336198}.
Q9Y4H2 IRS2 S162 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}.
Q9UNZ2 NSFL1C S284 Sugiyama NSFL1 cofactor p47 (UBX domain-containing protein 2C) (p97 cofactor p47) Reduces the ATPase activity of VCP (By similarity). Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Inhibits the activity of CTSL (in vitro) (PubMed:15498563). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase (PubMed:23649807). Also, regulates spindle orientation during mitosis (PubMed:23649807). {ECO:0000250|UniProtKB:O35987, ECO:0000269|PubMed:15498563, ECO:0000269|PubMed:23649807}.
P07332 FES S716 Sugiyama Tyrosine-protein kinase Fes/Fps (EC 2.7.10.2) (Feline sarcoma/Fujinami avian sarcoma oncogene homolog) (Proto-oncogene c-Fes) (Proto-oncogene c-Fps) (p93c-fes) Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28. {ECO:0000269|PubMed:11509660, ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:15485904, ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:17595334, ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:19001085, ECO:0000269|PubMed:19051325, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:2656706, ECO:0000269|PubMed:8955135}.
P09110 ACAA1 S206 Sugiyama 3-ketoacyl-CoA thiolase, peroxisomal (EC 2.3.1.16) (Acetyl-CoA C-myristoyltransferase) (EC 2.3.1.155) (Acetyl-CoA acyltransferase) (EC 2.3.1.9) (Beta-ketothiolase) (Peroxisomal 3-oxoacyl-CoA thiolase) Responsible for the thiolytic cleavage of straight chain 3-keto fatty acyl-CoAs (3-oxoacyl-CoAs) (PubMed:11734571, PubMed:2882519). Plays an important role in fatty acid peroxisomal beta-oxidation (PubMed:11734571, PubMed:2882519). Catalyzes the cleavage of short, medium, long, and very long straight chain 3-oxoacyl-CoAs (PubMed:11734571, PubMed:2882519). {ECO:0000305|PubMed:11734571, ECO:0000305|PubMed:2882519}.
Q8WZA9 IRGQ S538 Sugiyama 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}.
P18206 VCL S1113 GPS6|SIGNOR|ELM|EPSD Vinculin (Metavinculin) (MV) Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}.
Q9BWF3 RBM4 S343 Sugiyama RNA-binding protein 4 (Lark homolog) (hLark) (RNA-binding motif protein 4) (RNA-binding motif protein 4a) RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5'-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro. {ECO:0000269|PubMed:12628928, ECO:0000269|PubMed:16260624, ECO:0000269|PubMed:16777844, ECO:0000269|PubMed:16934801, ECO:0000269|PubMed:17284590, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:19801630, ECO:0000269|PubMed:21343338, ECO:0000269|PubMed:21518792, ECO:0000269|PubMed:37548402}.
Q15084 PDIA6 S205 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}.
P62258 YWHAE S156 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}.
O43488 AKR7A2 S56 Sugiyama Aflatoxin B1 aldehyde reductase member 2 (EC 1.1.1.n11) (AFB1 aldehyde reductase 1) (AFB1-AR 1) (Aldoketoreductase 7) (Succinic semialdehyde reductase) (SSA reductase) Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen. {ECO:0000269|PubMed:17591773, ECO:0000269|PubMed:9576847}.
P43403 ZAP70 S260 Sugiyama Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase) Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.
Q9NQR4 NIT2 S207 Sugiyama Omega-amidase NIT2 (EC 3.5.1.3) (Nitrilase homolog 2) Has omega-amidase activity (PubMed:19595734, PubMed:22674578). The role of omega-amidase is to remove potentially toxic intermediates by converting 2-oxoglutaramate and 2-oxosuccinamate to biologically useful 2-oxoglutarate and oxaloacetate, respectively (PubMed:19595734). {ECO:0000269|PubMed:19595734, ECO:0000269|PubMed:22674578}.
P51617 IRAK1 S568 Sugiyama 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}.
P17987 TCP1 S27 Sugiyama T-complex protein 1 subunit alpha (TCP-1-alpha) (EC 3.6.1.-) (CCT-alpha) (Chaperonin containing T-complex polypeptide 1 subunit 1) Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}.
O60664 PLIN3 S76 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}.
Q9NZV8 KCND2 S438 ELM A-type voltage-gated potassium channel KCND2 (Potassium voltage-gated channel subfamily D member 2) (Voltage-gated potassium channel subunit Kv4.2) Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:11507158, PubMed:14623880, PubMed:14695263, PubMed:14980201, PubMed:15454437, PubMed:16934482, PubMed:19171772, PubMed:24501278, PubMed:24811166, PubMed:34552243, PubMed:35597238). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:14623880, PubMed:14980201, PubMed:15454437, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (PubMed:35597238). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10551270, ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278, ECO:0000269|PubMed:24811166, ECO:0000269|PubMed:34552243, ECO:0000269|PubMed:35597238}.
Q9H4A4 RNPEP S29 Sugiyama Aminopeptidase B (AP-B) (EC 3.4.11.6) (Arginine aminopeptidase) (Arginyl aminopeptidase) Exopeptidase which selectively removes arginine and/or lysine residues from the N-terminus of several peptide substrates including Arg(0)-Leu-enkephalin, Arg(0)-Met-enkephalin and Arg(-1)-Lys(0)-somatostatin-14. Can hydrolyze leukotriene A4 (LTA-4) into leukotriene B4 (LTB-4) (By similarity). {ECO:0000250}.
Q16512 PKN1 S296 Sugiyama Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.
P29144 TPP2 S25 Sugiyama 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}.
O00273 DFFA S90 Sugiyama DNA fragmentation factor subunit alpha (DNA fragmentation factor 45 kDa subunit) (DFF-45) (Inhibitor of CAD) (ICAD) Inhibitor of the caspase-activated DNase (DFF40).
Q8N568 DCLK2 S181 Sugiyama Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}.
P20933 AGA S49 Sugiyama N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (EC 3.5.1.26) (Aspartylglucosaminidase) (Glycosylasparaginase) (N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase) [Cleaved into: Glycosylasparaginase alpha chain; Glycosylasparaginase beta chain] Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins. {ECO:0000269|PubMed:1703489, ECO:0000269|PubMed:1904874, ECO:0000269|PubMed:2401370}.
P55036 PSMD4 S242 Sugiyama 26S proteasome non-ATPase regulatory subunit 4 (26S proteasome regulatory subunit RPN10) (26S proteasome regulatory subunit S5A) (Antisecretory factor 1) (AF) (ASF) (Multiubiquitin chain-binding protein) 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. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:15826667}.
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reactome_id name p -log10_p
R-HSA-8986944 Transcriptional Regulation by MECP2 0.000068 4.168
R-HSA-9022534 Loss of MECP2 binding ability to 5hmC-DNA 0.000568 3.246
R-HSA-9022537 Loss of MECP2 binding ability to the NCoR/SMRT complex 0.000380 3.420
R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters 0.000724 3.140
R-HSA-9022692 Regulation of MECP2 expression and activity 0.000613 3.213
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 0.001056 2.976
R-HSA-4839735 Signaling by AXIN mutants 0.002294 2.639
R-HSA-9005891 Loss of function of MECP2 in Rett syndrome 0.002750 2.561
R-HSA-9697154 Disorders of Nervous System Development 0.002750 2.561
R-HSA-9005895 Pervasive developmental disorders 0.002750 2.561
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 0.002372 2.625
R-HSA-195253 Degradation of beta-catenin by the destruction complex 0.002432 2.614
R-HSA-4641265 Repression of WNT target genes 0.002750 2.561
R-HSA-9022538 Loss of MECP2 binding ability to 5mC-DNA 0.003433 2.464
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 0.003599 2.444
R-HSA-9022927 MECP2 regulates transcription of genes involved in GABA signaling 0.004889 2.311
R-HSA-4791275 Signaling by WNT in cancer 0.004357 2.361
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 0.004747 2.324
R-HSA-9700206 Signaling by ALK in cancer 0.004747 2.324
R-HSA-9675151 Disorders of Developmental Biology 0.005841 2.234
R-HSA-74713 IRS activation 0.006580 2.182
R-HSA-9022535 Loss of phosphorylation of MECP2 at T308 0.006580 2.182
R-HSA-909733 Interferon alpha/beta signaling 0.007249 2.140
R-HSA-9833576 CDH11 homotypic and heterotypic interactions 0.008499 2.071
R-HSA-201681 TCF dependent signaling in response to WNT 0.008604 2.065
R-HSA-9764302 Regulation of CDH19 Expression and Function 0.008499 2.071
R-HSA-3371556 Cellular response to heat stress 0.009154 2.038
R-HSA-6807004 Negative regulation of MET activity 0.009377 2.028
R-HSA-5467345 Deletions in the AXIN1 gene destabilize the destruction complex 0.016933 1.771
R-HSA-9022707 MECP2 regulates transcription factors 0.012987 1.887
R-HSA-112412 SOS-mediated signalling 0.012987 1.887
R-HSA-9022702 MECP2 regulates transcription of neuronal ligands 0.021227 1.673
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex 0.021227 1.673
R-HSA-9645460 Alpha-protein kinase 1 signaling pathway 0.024347 1.614
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex 0.024347 1.614
R-HSA-5467337 APC truncation mutants have impaired AXIN binding 0.024347 1.614
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex 0.024347 1.614
R-HSA-5339716 Signaling by GSK3beta mutants 0.027641 1.558
R-HSA-4839743 Signaling by CTNNB1 phospho-site mutants 0.031104 1.507
R-HSA-5358751 CTNNB1 S45 mutants aren't phosphorylated 0.031104 1.507
R-HSA-5358752 CTNNB1 T41 mutants aren't phosphorylated 0.031104 1.507
R-HSA-5358749 CTNNB1 S37 mutants aren't phosphorylated 0.031104 1.507
R-HSA-5358747 CTNNB1 S33 mutants aren't phosphorylated 0.031104 1.507
R-HSA-428930 Thromboxane signalling through TP receptor 0.015231 1.817
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane 0.019535 1.709
R-HSA-9615710 Late endosomal microautophagy 0.022740 1.643
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 0.024443 1.612
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 0.026214 1.581
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 0.026214 1.581
R-HSA-1855170 IPs transport between nucleus and cytosol 0.029955 1.524
R-HSA-159227 Transport of the SLBP independent Mature mRNA 0.029955 1.524
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 0.031925 1.496
R-HSA-191859 snRNP Assembly 0.028823 1.540
R-HSA-194441 Metabolism of non-coding RNA 0.028823 1.540
R-HSA-209543 p75NTR recruits signalling complexes 0.031104 1.507
R-HSA-9762292 Regulation of CDH11 function 0.021227 1.673
R-HSA-198203 PI3K/AKT activation 0.021227 1.673
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT) 0.022740 1.643
R-HSA-525793 Myogenesis 0.018034 1.744
R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling 0.010637 1.973
R-HSA-4839744 Signaling by APC mutants 0.024347 1.614
R-HSA-4839748 Signaling by AMER1 mutants 0.027641 1.558
R-HSA-195721 Signaling by WNT 0.022116 1.655
R-HSA-74749 Signal attenuation 0.021227 1.673
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 0.031925 1.496
R-HSA-8876384 Listeria monocytogenes entry into host cells 0.011523 1.938
R-HSA-8931987 RUNX1 regulates estrogen receptor mediated transcription 0.012987 1.887
R-HSA-9933387 RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression 0.024443 1.612
R-HSA-2980766 Nuclear Envelope Breakdown 0.026203 1.582
R-HSA-982772 Growth hormone receptor signaling 0.013929 1.856
R-HSA-1169408 ISG15 antiviral mechanism 0.014682 1.833
R-HSA-9705683 SARS-CoV-2-host interactions 0.028143 1.551
R-HSA-2586552 Signaling by Leptin 0.021227 1.673
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 0.016228 1.790
R-HSA-913531 Interferon Signaling 0.022878 1.641
R-HSA-5602566 TICAM1 deficiency - HSE 0.033580 1.474
R-HSA-9861559 PDH complex synthesizes acetyl-CoA from PYR 0.034728 1.459
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 0.036064 1.443
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 0.034515 1.462
R-HSA-380259 Loss of Nlp from mitotic centrosomes 0.034515 1.462
R-HSA-392518 Signal amplification 0.033962 1.469
R-HSA-180746 Nuclear import of Rev protein 0.033962 1.469
R-HSA-9029558 NR1H2 & NR1H3 regulate gene expression linked to lipogenesis 0.034728 1.459
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex 0.042434 1.372
R-HSA-196299 Beta-catenin phosphorylation cascade 0.042434 1.372
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 0.045125 1.346
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 0.047551 1.323
R-HSA-8854518 AURKA Activation by TPX2 0.039183 1.407
R-HSA-193639 p75NTR signals via NF-kB 0.042434 1.372
R-HSA-399955 SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion 0.046504 1.333
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation 0.038507 1.414
R-HSA-180910 Vpr-mediated nuclear import of PICs 0.040466 1.393
R-HSA-399956 CRMPs in Sema3A signaling 0.038507 1.414
R-HSA-177243 Interactions of Rev with host cellular proteins 0.047551 1.323
R-HSA-176033 Interactions of Vpr with host cellular proteins 0.047551 1.323
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 0.040466 1.393
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 0.042764 1.369
R-HSA-168276 NS1 Mediated Effects on Host Pathways 0.045125 1.346
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 0.042434 1.372
R-HSA-162582 Signal Transduction 0.041845 1.378
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 0.043797 1.359
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... 0.037589 1.425
R-HSA-5602571 TRAF3 deficiency - HSE 0.049947 1.301
R-HSA-5339700 Signaling by TCF7L2 mutants 0.049947 1.301
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 0.050039 1.301
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 0.051407 1.289
R-HSA-5684045 Defective ABCD1 causes ALD 0.066037 1.180
R-HSA-380287 Centrosome maturation 0.055241 1.258
R-HSA-76009 Platelet Aggregation (Plug Formation) 0.063402 1.198
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 0.063402 1.198
R-HSA-9613829 Chaperone Mediated Autophagy 0.059512 1.225
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 0.073601 1.133
R-HSA-76002 Platelet activation, signaling and aggregation 0.067648 1.170
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 0.066253 1.179
R-HSA-9006931 Signaling by Nuclear Receptors 0.066766 1.175
R-HSA-4420097 VEGFA-VEGFR2 Pathway 0.072038 1.142
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 0.069163 1.160
R-HSA-9694516 SARS-CoV-2 Infection 0.054231 1.266
R-HSA-9020591 Interleukin-12 signaling 0.057214 1.242
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 0.074335 1.129
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 0.076662 1.115
R-HSA-5368598 Negative regulation of TCF-dependent signaling by DVL-interacting proteins 0.081856 1.087
R-HSA-392023 Adrenaline signalling through Alpha-2 adrenergic receptor 0.081856 1.087
R-HSA-5660862 Defective SLC7A7 causes lysinuric protein intolerance (LPI) 0.081856 1.087
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death 0.097408 1.011
R-HSA-9673768 Signaling by membrane-tethered fusions of PDGFRA or PDGFRB 0.112697 0.948
R-HSA-8985586 SLIT2:ROBO1 increases RHOA activity 0.127728 0.894
R-HSA-5576894 Phase 1 - inactivation of fast Na+ channels 0.127728 0.894
R-HSA-9027283 Erythropoietin activates STAT5 0.142506 0.846
R-HSA-9912481 Branched-chain ketoacid dehydrogenase kinase deficiency 0.142506 0.846
R-HSA-8951430 RUNX3 regulates WNT signaling 0.157034 0.804
R-HSA-2562578 TRIF-mediated programmed cell death 0.157034 0.804
R-HSA-5619108 Defective SLC27A4 causes ichthyosis prematurity syndrome (IPS) 0.157034 0.804
R-HSA-446107 Type I hemidesmosome assembly 0.171317 0.766
R-HSA-9828211 Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation 0.171317 0.766
R-HSA-9613354 Lipophagy 0.185359 0.732
R-HSA-201688 WNT mediated activation of DVL 0.185359 0.732
R-HSA-9027277 Erythropoietin activates Phospholipase C gamma (PLCG) 0.199163 0.701
R-HSA-390450 Folding of actin by CCT/TriC 0.199163 0.701
R-HSA-112308 Presynaptic depolarization and calcium channel opening 0.212735 0.672
R-HSA-429947 Deadenylation of mRNA 0.093825 1.028
R-HSA-9824878 Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 0.226077 0.646
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 0.239194 0.621
R-HSA-975144 IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation 0.239194 0.621
R-HSA-937039 IRAK1 recruits IKK complex 0.239194 0.621
R-HSA-9820865 Z-decay: degradation of maternal mRNAs by zygotically expressed factors 0.239194 0.621
R-HSA-9027284 Erythropoietin activates RAS 0.277231 0.557
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment 0.277231 0.557
R-HSA-9668328 Sealing of the nuclear envelope (NE) by ESCRT-III 0.143946 0.842
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins 0.289484 0.538
R-HSA-5250924 B-WICH complex positively regulates rRNA expression 0.087787 1.057
R-HSA-4641257 Degradation of AXIN 0.173738 0.760
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins 0.313372 0.504
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair 0.325015 0.488
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 0.122855 0.911
R-HSA-937041 IKK complex recruitment mediated by RIP1 0.336461 0.473
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 0.086207 1.064
R-HSA-9934037 Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) 0.347713 0.459
R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER 0.369651 0.432
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 0.187235 0.728
R-HSA-72649 Translation initiation complex formation 0.285905 0.544
R-HSA-72702 Ribosomal scanning and start codon recognition 0.298461 0.525
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 0.200161 0.699
R-HSA-5620916 VxPx cargo-targeting to cilium 0.347713 0.459
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 0.091199 1.040
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7 0.226077 0.646
R-HSA-936964 Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) 0.301530 0.521
R-HSA-354192 Integrin signaling 0.143946 0.842
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 0.310982 0.507
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 0.252243 0.598
R-HSA-8876493 InlA-mediated entry of Listeria monocytogenes into host cells 0.212735 0.672
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 0.354369 0.451
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 0.162103 0.790
R-HSA-9609690 HCMV Early Events 0.164617 0.784
R-HSA-8849472 PTK6 Down-Regulation 0.112697 0.948
R-HSA-5689901 Metalloprotease DUBs 0.104470 0.981
R-HSA-9664420 Killing mechanisms 0.289484 0.538
R-HSA-9673324 WNT5:FZD7-mediated leishmania damping 0.289484 0.538
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 0.173738 0.760
R-HSA-5674135 MAP2K and MAPK activation 0.204402 0.690
R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling 0.301530 0.521
R-HSA-3214815 HDACs deacetylate histones 0.292187 0.534
R-HSA-140342 Apoptosis induced DNA fragmentation 0.199163 0.701
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 0.191519 0.718
R-HSA-2428928 IRS-related events triggered by IGF1R 0.329673 0.482
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 0.198217 0.703
R-HSA-9656223 Signaling by RAF1 mutants 0.204402 0.690
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 0.235598 0.628
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 0.235598 0.628
R-HSA-9649948 Signaling downstream of RAS mutants 0.235598 0.628
R-HSA-8856828 Clathrin-mediated endocytosis 0.296565 0.528
R-HSA-68952 DNA replication initiation 0.199163 0.701
R-HSA-209560 NF-kB is activated and signals survival 0.226077 0.646
R-HSA-9796292 Formation of axial mesoderm 0.252089 0.598
R-HSA-804914 Transport of fatty acids 0.264767 0.577
R-HSA-399954 Sema3A PAK dependent Axon repulsion 0.277231 0.557
R-HSA-9603798 Class I peroxisomal membrane protein import 0.289484 0.538
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA 0.167698 0.775
R-HSA-9764561 Regulation of CDH1 Function 0.101248 0.995
R-HSA-429914 Deadenylation-dependent mRNA decay 0.108270 0.965
R-HSA-181429 Serotonin Neurotransmitter Release Cycle 0.325015 0.488
R-HSA-73980 RNA Polymerase III Transcription Termination 0.325015 0.488
R-HSA-350054 Notch-HLH transcription pathway 0.380342 0.420
R-HSA-9609646 HCMV Infection 0.181854 0.740
R-HSA-6802949 Signaling by RAS mutants 0.235598 0.628
R-HSA-112399 IRS-mediated signalling 0.304727 0.516
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 0.153968 0.813
R-HSA-427413 NoRC negatively regulates rRNA expression 0.390780 0.408
R-HSA-6804760 Regulation of TP53 Activity through Methylation 0.325015 0.488
R-HSA-2428924 IGF1R signaling cascade 0.348223 0.458
R-HSA-9603381 Activated NTRK3 signals through PI3K 0.157034 0.804
R-HSA-937042 IRAK2 mediated activation of TAK1 complex 0.185359 0.732
R-HSA-111447 Activation of BAD and translocation to mitochondria 0.277231 0.557
R-HSA-212676 Dopamine Neurotransmitter Release Cycle 0.380342 0.420
R-HSA-74751 Insulin receptor signalling cascade 0.348223 0.458
R-HSA-166166 MyD88-independent TLR4 cascade 0.157586 0.802
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 0.141869 0.848
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 0.157586 0.802
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 0.315637 0.501
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 0.354369 0.451
R-HSA-5617833 Cilium Assembly 0.150392 0.823
R-HSA-5620920 Cargo trafficking to the periciliary membrane 0.390780 0.408
R-HSA-9663891 Selective autophagy 0.231073 0.636
R-HSA-9020702 Interleukin-1 signaling 0.299622 0.523
R-HSA-205025 NADE modulates death signalling 0.097408 1.011
R-HSA-1483226 Synthesis of PI 0.212735 0.672
R-HSA-9706019 RHOBTB3 ATPase cycle 0.212735 0.672
R-HSA-204174 Regulation of pyruvate dehydrogenase (PDH) complex 0.121005 0.917
R-HSA-5635838 Activation of SMO 0.289484 0.538
R-HSA-168325 Viral Messenger RNA Synthesis 0.115475 0.938
R-HSA-429958 mRNA decay by 3' to 5' exoribonuclease 0.336461 0.473
R-HSA-69473 G2/M DNA damage checkpoint 0.166218 0.779
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 0.285905 0.544
R-HSA-74752 Signaling by Insulin receptor 0.253660 0.596
R-HSA-68877 Mitotic Prometaphase 0.296988 0.527
R-HSA-6794361 Neurexins and neuroligins 0.273326 0.563
R-HSA-9610379 HCMV Late Events 0.181891 0.740
R-HSA-9842663 Signaling by LTK 0.239194 0.621
R-HSA-68886 M Phase 0.253860 0.595
R-HSA-9018519 Estrogen-dependent gene expression 0.123457 0.908
R-HSA-9759475 Regulation of CDH11 Expression and Function 0.121005 0.917
R-HSA-3371511 HSF1 activation 0.167698 0.775
R-HSA-168273 Influenza Viral RNA Transcription and Replication 0.342500 0.465
R-HSA-182971 EGFR downregulation 0.132361 0.878
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 0.143946 0.842
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 0.135766 0.867
R-HSA-975155 MyD88 dependent cascade initiated on endosome 0.154392 0.811
R-HSA-9612973 Autophagy 0.346345 0.460
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 0.364488 0.438
R-HSA-428890 Role of ABL in ROBO-SLIT signaling 0.157034 0.804
R-HSA-428540 Activation of RAC1 0.226077 0.646
R-HSA-877312 Regulation of IFNG signaling 0.239194 0.621
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 0.277231 0.557
R-HSA-6811440 Retrograde transport at the Trans-Golgi-Network 0.241874 0.616
R-HSA-445355 Smooth Muscle Contraction 0.279618 0.553
R-HSA-373755 Semaphorin interactions 0.122855 0.911
R-HSA-193704 p75 NTR receptor-mediated signalling 0.121000 0.917
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 0.167314 0.776
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 0.177250 0.751
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 0.108270 0.965
R-HSA-975871 MyD88 cascade initiated on plasma membrane 0.285757 0.544
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 0.285757 0.544
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 0.285757 0.544
R-HSA-9683610 Maturation of nucleoprotein 0.252089 0.598
R-HSA-168638 NOD1/2 Signaling Pathway 0.155734 0.808
R-HSA-1852241 Organelle biogenesis and maintenance 0.362290 0.441
R-HSA-6794362 Protein-protein interactions at synapses 0.213291 0.671
R-HSA-1632852 Macroautophagy 0.285192 0.545
R-HSA-199991 Membrane Trafficking 0.256121 0.592
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 0.078512 1.105
R-HSA-9754560 SARS-CoV-2 modulates autophagy 0.212735 0.672
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 0.252089 0.598
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 0.277231 0.557
R-HSA-9933946 Formation of the embryonic stem cell BAF (esBAF) complex 0.277231 0.557
R-HSA-1483148 Synthesis of PG 0.301530 0.521
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium 0.347713 0.459
R-HSA-5578749 Transcriptional regulation by small RNAs 0.158019 0.801
R-HSA-912694 Regulation of IFNA/IFNB signaling 0.380342 0.420
R-HSA-9766229 Degradation of CDH1 0.254447 0.594
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 0.151223 0.820
R-HSA-5693532 DNA Double-Strand Break Repair 0.170576 0.768
R-HSA-5693606 DNA Double Strand Break Response 0.138109 0.860
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 0.320163 0.495
R-HSA-8939211 ESR-mediated signaling 0.277387 0.557
R-HSA-9861718 Regulation of pyruvate metabolism 0.235598 0.628
R-HSA-3858494 Beta-catenin independent WNT signaling 0.266395 0.574
R-HSA-390696 Adrenoceptors 0.171317 0.766
R-HSA-4419969 Depolymerization of the Nuclear Lamina 0.325015 0.488
R-HSA-109704 PI3K Cascade 0.260739 0.584
R-HSA-5688426 Deubiquitination 0.101819 0.992
R-HSA-390247 Beta-oxidation of very long chain fatty acids 0.173738 0.760
R-HSA-9823730 Formation of definitive endoderm 0.347713 0.459
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 0.369651 0.432
R-HSA-9033500 TYSND1 cleaves peroxisomal proteins 0.127728 0.894
R-HSA-9735871 SARS-CoV-1 targets host intracellular signalling and regulatory pathways 0.277231 0.557
R-HSA-399997 Acetylcholine regulates insulin secretion 0.301530 0.521
R-HSA-6784531 tRNA processing in the nucleus 0.119143 0.924
R-HSA-9694631 Maturation of nucleoprotein 0.336461 0.473
R-HSA-392517 Rap1 signalling 0.336461 0.473
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 0.369651 0.432
R-HSA-983189 Kinesins 0.323457 0.490
R-HSA-69620 Cell Cycle Checkpoints 0.339452 0.469
R-HSA-75153 Apoptotic execution phase 0.235598 0.628
R-HSA-2046106 alpha-linolenic acid (ALA) metabolism 0.179813 0.745
R-HSA-1483249 Inositol phosphate metabolism 0.355245 0.449
R-HSA-1640170 Cell Cycle 0.185121 0.733
R-HSA-8849932 Synaptic adhesion-like molecules 0.325015 0.488
R-HSA-166208 mTORC1-mediated signalling 0.380342 0.420
R-HSA-2046104 alpha-linolenic (omega3) and linoleic (omega6) acid metabolism 0.241874 0.616
R-HSA-177929 Signaling by EGFR 0.298461 0.525
R-HSA-68875 Mitotic Prophase 0.197692 0.704
R-HSA-194138 Signaling by VEGF 0.093848 1.028
R-HSA-430116 GP1b-IX-V activation signalling 0.185359 0.732
R-HSA-391908 Prostanoid ligand receptors 0.212735 0.672
R-HSA-9931510 Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... 0.104470 0.981
R-HSA-198323 AKT phosphorylates targets in the cytosol 0.239194 0.621
R-HSA-140534 Caspase activation via Death Receptors in the presence of ligand 0.289484 0.538
R-HSA-6787450 tRNA modification in the mitochondrion 0.301530 0.521
R-HSA-4086398 Ca2+ pathway 0.162103 0.790
R-HSA-73887 Death Receptor Signaling 0.173378 0.761
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 0.126608 0.898
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 0.153968 0.813
R-HSA-9034015 Signaling by NTRK3 (TRKC) 0.369651 0.432
R-HSA-446353 Cell-extracellular matrix interactions 0.277231 0.557
R-HSA-210991 Basigin interactions 0.358775 0.445
R-HSA-376176 Signaling by ROBO receptors 0.330164 0.481
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription 0.126652 0.897
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 0.325015 0.488
R-HSA-9909396 Circadian clock 0.111598 0.952
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 0.161696 0.791
R-HSA-70171 Glycolysis 0.294996 0.530
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 0.140993 0.851
R-HSA-9671555 Signaling by PDGFR in disease 0.369651 0.432
R-HSA-5685942 HDR through Homologous Recombination (HRR) 0.366599 0.436
R-HSA-109581 Apoptosis 0.369425 0.432
R-HSA-417957 P2Y receptors 0.264767 0.577
R-HSA-422475 Axon guidance 0.263287 0.580
R-HSA-9616222 Transcriptional regulation of granulopoiesis 0.335874 0.474
R-HSA-5357801 Programmed Cell Death 0.189531 0.722
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 0.380342 0.420
R-HSA-9675108 Nervous system development 0.234183 0.630
R-HSA-8983711 OAS antiviral response 0.239194 0.621
R-HSA-418038 Nucleotide-like (purinergic) receptors 0.325015 0.488
R-HSA-5218920 VEGFR2 mediated vascular permeability 0.198217 0.703
R-HSA-391903 Eicosanoid ligand-binding receptors 0.347713 0.459
R-HSA-9024446 NR1H2 and NR1H3-mediated signaling 0.178744 0.748
R-HSA-450294 MAP kinase activation 0.329673 0.482
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 0.204402 0.690
R-HSA-9860931 Response of endothelial cells to shear stress 0.313523 0.504
R-HSA-448424 Interleukin-17 signaling 0.384772 0.415
R-HSA-5218859 Regulated Necrosis 0.372680 0.429
R-HSA-844456 The NLRP3 inflammasome 0.336461 0.473
R-HSA-9012852 Signaling by NOTCH3 0.292187 0.534
R-HSA-162599 Late Phase of HIV Life Cycle 0.292767 0.533
R-HSA-70326 Glucose metabolism 0.387491 0.412
R-HSA-9855142 Cellular responses to mechanical stimuli 0.364488 0.438
R-HSA-5362517 Signaling by Retinoic Acid 0.323457 0.490
R-HSA-5619102 SLC transporter disorders 0.211325 0.675
R-HSA-5619115 Disorders of transmembrane transporters 0.306662 0.513
R-HSA-1280215 Cytokine Signaling in Immune system 0.245142 0.611
R-HSA-381038 XBP1(S) activates chaperone genes 0.081353 1.090
R-HSA-9679506 SARS-CoV Infections 0.189582 0.722
R-HSA-8853659 RET signaling 0.167698 0.775
R-HSA-6806834 Signaling by MET 0.191519 0.718
R-HSA-1266695 Interleukin-7 signaling 0.099107 1.004
R-HSA-381070 IRE1alpha activates chaperones 0.096327 1.016
R-HSA-162587 HIV Life Cycle 0.350192 0.456
R-HSA-2028269 Signaling by Hippo 0.313372 0.504
R-HSA-9679504 Translation of Replicase and Assembly of the Replication Transcription Complex 0.325015 0.488
R-HSA-9694676 Translation of Replicase and Assembly of the Replication Transcription Complex 0.380342 0.420
R-HSA-211000 Gene Silencing by RNA 0.332078 0.479
R-HSA-381119 Unfolded Protein Response (UPR) 0.277648 0.557
R-HSA-447115 Interleukin-12 family signaling 0.083763 1.077
R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC 0.390853 0.408
R-HSA-1369062 ABC transporters in lipid homeostasis 0.390853 0.408
R-HSA-3000170 Syndecan interactions 0.390853 0.408
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 0.390853 0.408
R-HSA-5693538 Homology Directed Repair 0.392069 0.407
R-HSA-2219528 PI3K/AKT Signaling in Cancer 0.392069 0.407
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 0.396639 0.402
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 0.396639 0.402
R-HSA-199992 trans-Golgi Network Vesicle Budding 0.396762 0.401
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 0.396762 0.401
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 0.399677 0.398
R-HSA-446728 Cell junction organization 0.399813 0.398
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 0.401186 0.397
R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC 0.401186 0.397
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex 0.401186 0.397
R-HSA-8863678 Neurodegenerative Diseases 0.401186 0.397
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 0.401186 0.397
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 0.402717 0.395
R-HSA-72306 tRNA processing 0.403929 0.394
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 0.410293 0.387
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 0.410293 0.387
R-HSA-174411 Polymerase switching on the C-strand of the telomere 0.411345 0.386
R-HSA-9839394 TGFBR3 expression 0.411345 0.386
R-HSA-9932451 SWI/SNF chromatin remodelers 0.411345 0.386
R-HSA-9932444 ATP-dependent chromatin remodelers 0.411345 0.386
R-HSA-3214842 HDMs demethylate histones 0.411345 0.386
R-HSA-3000157 Laminin interactions 0.411345 0.386
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) 0.414543 0.382
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 0.414823 0.382
R-HSA-9764265 Regulation of CDH1 Expression and Function 0.415363 0.382
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 0.415363 0.382
R-HSA-162909 Host Interactions of HIV factors 0.419343 0.377
R-HSA-69278 Cell Cycle, Mitotic 0.420072 0.377
R-HSA-5689603 UCH proteinases 0.420412 0.376
R-HSA-1980143 Signaling by NOTCH1 0.420412 0.376
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 0.421332 0.375
R-HSA-400042 Adrenaline,noradrenaline inhibits insulin secretion 0.421332 0.375
R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway 0.421332 0.375
R-HSA-2046105 Linoleic acid (LA) metabolism 0.421332 0.375
R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus 0.421332 0.375
R-HSA-9865118 Diseases of branched-chain amino acid catabolism 0.421332 0.375
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway 0.421332 0.375
R-HSA-9678108 SARS-CoV-1 Infection 0.422960 0.374
R-HSA-445095 Interaction between L1 and Ankyrins 0.431150 0.365
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 0.431150 0.365
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 0.431150 0.365
R-HSA-416482 G alpha (12/13) signalling events 0.432059 0.364
R-HSA-69481 G2/M Checkpoints 0.437302 0.359
R-HSA-114608 Platelet degranulation 0.437302 0.359
R-HSA-168255 Influenza Infection 0.438079 0.358
R-HSA-77387 Insulin receptor recycling 0.440802 0.356
R-HSA-9638334 Iron assimilation using enterobactin 0.440802 0.356
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 0.440802 0.356
R-HSA-5620971 Pyroptosis 0.440802 0.356
R-HSA-622312 Inflammasomes 0.440802 0.356
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 0.443580 0.353
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 0.443580 0.353
R-HSA-5693607 Processing of DNA double-strand break ends 0.449293 0.347
R-HSA-9006335 Signaling by Erythropoietin 0.450290 0.347
R-HSA-9709570 Impaired BRCA2 binding to RAD51 0.450290 0.347
R-HSA-5656169 Termination of translesion DNA synthesis 0.450290 0.347
R-HSA-199418 Negative regulation of the PI3K/AKT network 0.450634 0.346
R-HSA-9843745 Adipogenesis 0.459451 0.338
R-HSA-68962 Activation of the pre-replicative complex 0.459619 0.338
R-HSA-114452 Activation of BH3-only proteins 0.459619 0.338
R-HSA-8856688 Golgi-to-ER retrograde transport 0.463837 0.334
R-HSA-69275 G2/M Transition 0.464253 0.333
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 0.466229 0.331
R-HSA-390918 Peroxisomal lipid metabolism 0.466229 0.331
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 0.468208 0.330
R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding 0.468789 0.329
R-HSA-162588 Budding and maturation of HIV virion 0.468789 0.329
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 0.468789 0.329
R-HSA-453274 Mitotic G2-G2/M phases 0.471655 0.326
R-HSA-6802957 Oncogenic MAPK signaling 0.471806 0.326
R-HSA-141424 Amplification of signal from the kinetochores 0.477348 0.321
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 0.477348 0.321
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 0.477348 0.321
R-HSA-111465 Apoptotic cleavage of cellular proteins 0.477805 0.321
R-HSA-168898 Toll-like Receptor Cascades 0.482686 0.316
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 0.486668 0.313
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 0.486668 0.313
R-HSA-5675482 Regulation of necroptotic cell death 0.486668 0.313
R-HSA-70268 Pyruvate metabolism 0.488325 0.311
R-HSA-72163 mRNA Splicing - Major Pathway 0.493627 0.307
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis 0.495381 0.305
R-HSA-5696394 DNA Damage Recognition in GG-NER 0.495381 0.305
R-HSA-9768727 Regulation of CDH1 posttranslational processing and trafficking to plasma membra... 0.495381 0.305
R-HSA-114508 Effects of PIP2 hydrolysis 0.495381 0.305
R-HSA-9619665 EGR2 and SOX10-mediated initiation of Schwann cell myelination 0.495381 0.305
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 0.500866 0.300
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding 0.503947 0.298
R-HSA-5696400 Dual Incision in GG-NER 0.503947 0.298
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 0.503947 0.298
R-HSA-9735869 SARS-CoV-1 modulates host translation machinery 0.503947 0.298
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 0.503947 0.298
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 0.503947 0.298
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 0.503947 0.298
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian expression 0.503947 0.298
R-HSA-5205647 Mitophagy 0.503947 0.298
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 0.509842 0.293
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 0.512368 0.290
R-HSA-1500931 Cell-Cell communication 0.512685 0.290
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 0.515128 0.288
R-HSA-156842 Eukaryotic Translation Elongation 0.520377 0.284
R-HSA-432720 Lysosome Vesicle Biogenesis 0.520647 0.283
R-HSA-111933 Calmodulin induced events 0.520647 0.283
R-HSA-111997 CaM pathway 0.520647 0.283
R-HSA-749476 RNA Polymerase III Abortive And Retractive Initiation 0.520647 0.283
R-HSA-163560 Triglyceride catabolism 0.520647 0.283
R-HSA-74158 RNA Polymerase III Transcription 0.520647 0.283
R-HSA-1296072 Voltage gated Potassium channels 0.528785 0.277
R-HSA-4641258 Degradation of DVL 0.528785 0.277
R-HSA-9762114 GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 0.528785 0.277
R-HSA-5689896 Ovarian tumor domain proteases 0.528785 0.277
R-HSA-196757 Metabolism of folate and pterines 0.528785 0.277
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 0.530760 0.275
R-HSA-212165 Epigenetic regulation of gene expression 0.532703 0.274
R-HSA-72172 mRNA Splicing 0.532869 0.273
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 0.536786 0.270
R-HSA-5213460 RIPK1-mediated regulated necrosis 0.536786 0.270
R-HSA-452723 Transcriptional regulation of pluripotent stem cells 0.536786 0.270
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 0.544651 0.264
R-HSA-8953750 Transcriptional Regulation by E2F6 0.544651 0.264
R-HSA-9929356 GSK3B-mediated proteasomal degradation of PD-L1(CD274) 0.544651 0.264
R-HSA-381771 Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) 0.544651 0.264
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 0.544651 0.264
R-HSA-9648002 RAS processing 0.544651 0.264
R-HSA-201556 Signaling by ALK 0.544651 0.264
R-HSA-6807878 COPI-mediated anterograde transport 0.546047 0.263
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 0.546047 0.263
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 0.546047 0.263
R-HSA-9646399 Aggrephagy 0.552384 0.258
R-HSA-9844594 Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 0.552384 0.258
R-HSA-9843743 Transcriptional regulation of brown and beige adipocyte differentiation 0.552384 0.258
R-HSA-3371568 Attenuation phase 0.552384 0.258
R-HSA-1251985 Nuclear signaling by ERBB4 0.552384 0.258
R-HSA-202433 Generation of second messenger molecules 0.552384 0.258
R-HSA-5260271 Diseases of Immune System 0.552384 0.258
R-HSA-5602358 Diseases associated with the TLR signaling cascade 0.552384 0.258
R-HSA-71240 Tryptophan catabolism 0.552384 0.258
R-HSA-5653656 Vesicle-mediated transport 0.555344 0.255
R-HSA-446652 Interleukin-1 family signaling 0.555882 0.255
R-HSA-8957275 Post-translational protein phosphorylation 0.556044 0.255
R-HSA-422356 Regulation of insulin secretion 0.556044 0.255
R-HSA-9609507 Protein localization 0.559840 0.252
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 0.559985 0.252
R-HSA-8853884 Transcriptional Regulation by VENTX 0.559985 0.252
R-HSA-73933 Resolution of Abasic Sites (AP sites) 0.559985 0.252
R-HSA-73817 Purine ribonucleoside monophosphate biosynthesis 0.559985 0.252
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... 0.559985 0.252
R-HSA-5423646 Aflatoxin activation and detoxification 0.559985 0.252
R-HSA-9614085 FOXO-mediated transcription 0.560984 0.251
R-HSA-9730414 MITF-M-regulated melanocyte development 0.563833 0.249
R-HSA-69618 Mitotic Spindle Checkpoint 0.565884 0.247
R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis 0.567458 0.246
R-HSA-5610783 Degradation of GLI2 by the proteasome 0.567458 0.246
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome 0.567458 0.246
R-HSA-9683701 Translation of Structural Proteins 0.567458 0.246
R-HSA-1989781 PPARA activates gene expression 0.567693 0.246
R-HSA-6798695 Neutrophil degranulation 0.571960 0.243
R-HSA-68882 Mitotic Anaphase 0.573903 0.241
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 0.574805 0.240
R-HSA-111996 Ca-dependent events 0.574805 0.240
R-HSA-400508 Incretin synthesis, secretion, and inactivation 0.574805 0.240
R-HSA-165159 MTOR signalling 0.574805 0.240
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 0.575460 0.240
R-HSA-2555396 Mitotic Metaphase and Anaphase 0.577231 0.239
R-HSA-418990 Adherens junctions interactions 0.580545 0.236
R-HSA-1433557 Signaling by SCF-KIT 0.582027 0.235
R-HSA-9006925 Intracellular signaling by second messengers 0.585198 0.233
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 0.588543 0.230
R-HSA-9907900 Proteasome assembly 0.589127 0.230
R-HSA-375280 Amine ligand-binding receptors 0.589127 0.230
R-HSA-5683826 Surfactant metabolism 0.589127 0.230
R-HSA-5619507 Activation of HOX genes during differentiation 0.589795 0.229
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 0.589795 0.229
R-HSA-5696398 Nucleotide Excision Repair 0.594459 0.226
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 0.596106 0.225
R-HSA-774815 Nucleosome assembly 0.596106 0.225
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 0.596106 0.225
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 0.596106 0.225
R-HSA-1489509 DAG and IP3 signaling 0.596106 0.225
R-HSA-5683057 MAPK family signaling cascades 0.598508 0.223
R-HSA-9692914 SARS-CoV-1-host interactions 0.599083 0.223
R-HSA-72165 mRNA Splicing - Minor Pathway 0.602968 0.220
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 0.602968 0.220
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 0.602968 0.220
R-HSA-9839373 Signaling by TGFBR3 0.602968 0.220
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 0.602968 0.220
R-HSA-9660826 Purinergic signaling in leishmaniasis infection 0.602968 0.220
R-HSA-9664424 Cell recruitment (pro-inflammatory response) 0.602968 0.220
R-HSA-9675135 Diseases of DNA repair 0.602968 0.220
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 0.603667 0.219
R-HSA-8953854 Metabolism of RNA 0.603861 0.219
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 0.608212 0.216
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 0.608212 0.216
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 0.608212 0.216
R-HSA-5673001 RAF/MAP kinase cascade 0.608735 0.216
R-HSA-162906 HIV Infection 0.609685 0.215
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 0.612717 0.213
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 0.616345 0.210
R-HSA-202403 TCR signaling 0.617183 0.210
R-HSA-109582 Hemostasis 0.620834 0.207
R-HSA-73893 DNA Damage Bypass 0.622863 0.206
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription 0.622863 0.206
R-HSA-1257604 PIP3 activates AKT signaling 0.625583 0.204
R-HSA-927802 Nonsense-Mediated Decay (NMD) 0.625995 0.203
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 0.625995 0.203
R-HSA-5684996 MAPK1/MAPK3 signaling 0.628349 0.202
R-HSA-168256 Immune System 0.631024 0.200
R-HSA-73894 DNA Repair 0.632023 0.199
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 0.635572 0.197
R-HSA-3371571 HSF1-dependent transactivation 0.635572 0.197
R-HSA-156584 Cytosolic sulfonation of small molecules 0.635572 0.197
R-HSA-70895 Branched-chain amino acid catabolism 0.635572 0.197
R-HSA-2514856 The phototransduction cascade 0.635572 0.197
R-HSA-5689880 Ub-specific processing proteases 0.637870 0.195
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... 0.638919 0.195
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 0.641335 0.193
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 0.644777 0.191
R-HSA-1221632 Meiotic synapsis 0.647854 0.189
R-HSA-432722 Golgi Associated Vesicle Biogenesis 0.647854 0.189
R-HSA-8956320 Nucleotide biosynthesis 0.647854 0.189
R-HSA-157118 Signaling by NOTCH 0.649526 0.187
R-HSA-72737 Cap-dependent Translation Initiation 0.651491 0.186
R-HSA-72613 Eukaryotic Translation Initiation 0.651491 0.186
R-HSA-373760 L1CAM interactions 0.651491 0.186
R-HSA-9007101 Rab regulation of trafficking 0.655603 0.183
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 0.659723 0.181
R-HSA-418597 G alpha (z) signalling events 0.659723 0.181
R-HSA-8878166 Transcriptional regulation by RUNX2 0.663713 0.178
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER 0.665508 0.177
R-HSA-193648 NRAGE signals death through JNK 0.665508 0.177
R-HSA-109606 Intrinsic Pathway for Apoptosis 0.665508 0.177
R-HSA-75893 TNF signaling 0.665508 0.177
R-HSA-1483166 Synthesis of PA 0.671194 0.173
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 0.671194 0.173
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 0.671668 0.173
R-HSA-73886 Chromosome Maintenance 0.671668 0.173
R-HSA-4839726 Chromatin organization 0.675487 0.170
R-HSA-6782135 Dual incision in TC-NER 0.676784 0.170
R-HSA-9029569 NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... 0.676784 0.170
R-HSA-9772572 Early SARS-CoV-2 Infection Events 0.676784 0.170
R-HSA-9816359 Maternal to zygotic transition (MZT) 0.679471 0.168
R-HSA-421270 Cell-cell junction organization 0.681072 0.167
R-HSA-9033241 Peroxisomal protein import 0.682280 0.166
R-HSA-180786 Extension of Telomeres 0.682280 0.166
R-HSA-352230 Amino acid transport across the plasma membrane 0.682280 0.166
R-HSA-8979227 Triglyceride metabolism 0.682280 0.166
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures 0.682280 0.166
R-HSA-8943724 Regulation of PTEN gene transcription 0.687682 0.163
R-HSA-1660661 Sphingolipid de novo biosynthesis 0.687682 0.163
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 0.687682 0.163
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 0.687682 0.163
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 0.687682 0.163
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 0.687682 0.163
R-HSA-2644603 Signaling by NOTCH1 in Cancer 0.687682 0.163
R-HSA-8939902 Regulation of RUNX2 expression and activity 0.692993 0.159
R-HSA-112043 PLC beta mediated events 0.692993 0.159
R-HSA-1268020 Mitochondrial protein import 0.698213 0.156
R-HSA-9707616 Heme signaling 0.698213 0.156
R-HSA-2262752 Cellular responses to stress 0.700304 0.155
R-HSA-187037 Signaling by NTRK1 (TRKA) 0.701977 0.154
R-HSA-8848021 Signaling by PTK6 0.703346 0.153
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 0.703346 0.153
R-HSA-69615 G1/S DNA Damage Checkpoints 0.703346 0.153
R-HSA-8953897 Cellular responses to stimuli 0.704751 0.152
R-HSA-1234174 Cellular response to hypoxia 0.713351 0.147
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 0.718227 0.144
R-HSA-9958863 SLC-mediated transport of amino acids 0.723020 0.141
R-HSA-112040 G-protein mediated events 0.723020 0.141
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 0.727732 0.138
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 0.727732 0.138
R-HSA-163685 Integration of energy metabolism 0.736564 0.133
R-HSA-9843940 Regulation of endogenous retroelements by KRAB-ZFP proteins 0.736917 0.133
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 0.736917 0.133
R-HSA-5632684 Hedgehog 'on' state 0.741394 0.130
R-HSA-9638482 Metal ion assimilation from the host 0.741394 0.130
R-HSA-9948299 Ribosome-associated quality control 0.743058 0.129
R-HSA-5358351 Signaling by Hedgehog 0.743058 0.129
R-HSA-9924644 Developmental Lineages of the Mammary Gland 0.745794 0.127
R-HSA-9664422 FCGR3A-mediated phagocytosis 0.749415 0.125
R-HSA-9664407 Parasite infection 0.749415 0.125
R-HSA-9664417 Leishmania phagocytosis 0.749415 0.125
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 0.750120 0.125
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 0.752542 0.123
R-HSA-1236394 Signaling by ERBB4 0.754372 0.122
R-HSA-425397 Transport of vitamins, nucleosides, and related molecules 0.754372 0.122
R-HSA-9658195 Leishmania infection 0.756799 0.121
R-HSA-9824443 Parasitic Infection Pathways 0.756799 0.121
R-HSA-397014 Muscle contraction 0.758398 0.120
R-HSA-71403 Citric acid cycle (TCA cycle) 0.758553 0.120
R-HSA-3000171 Non-integrin membrane-ECM interactions 0.758553 0.120
R-HSA-9694635 Translation of Structural Proteins 0.766702 0.115
R-HSA-383280 Nuclear Receptor transcription pathway 0.770673 0.113
R-HSA-4086400 PCP/CE pathway 0.770673 0.113
R-HSA-5619084 ABC transporter disorders 0.770673 0.113
R-HSA-191273 Cholesterol biosynthesis 0.770673 0.113
R-HSA-1266738 Developmental Biology 0.772322 0.112
R-HSA-199977 ER to Golgi Anterograde Transport 0.773509 0.112
R-HSA-9659379 Sensory processing of sound 0.774577 0.111
R-HSA-449147 Signaling by Interleukins 0.776311 0.110
R-HSA-166520 Signaling by NTRKs 0.776374 0.110
R-HSA-69242 S Phase 0.776374 0.110
R-HSA-9758941 Gastrulation 0.779208 0.108
R-HSA-9679191 Potential therapeutics for SARS 0.782011 0.107
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 0.782187 0.107
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 0.787523 0.104
R-HSA-9707564 Cytoprotection by HMOX1 0.789541 0.103
R-HSA-8878171 Transcriptional regulation by RUNX1 0.792140 0.101
R-HSA-74160 Gene expression (Transcription) 0.792280 0.101
R-HSA-1500620 Meiosis 0.796648 0.099
R-HSA-5687128 MAPK6/MAPK4 signaling 0.796648 0.099
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 0.800111 0.097
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 0.803516 0.095
R-HSA-390466 Chaperonin-mediated protein folding 0.806862 0.093
R-HSA-5633007 Regulation of TP53 Activity 0.808364 0.092
R-HSA-3247509 Chromatin modifying enzymes 0.809606 0.092
R-HSA-156902 Peptide chain elongation 0.810152 0.091
R-HSA-9645723 Diseases of programmed cell death 0.810152 0.091
R-HSA-212436 Generic Transcription Pathway 0.810798 0.091
R-HSA-112310 Neurotransmitter release cycle 0.816565 0.088
R-HSA-202424 Downstream TCR signaling 0.816565 0.088
R-HSA-73884 Base Excision Repair 0.816565 0.088
R-HSA-2467813 Separation of Sister Chromatids 0.818089 0.087
R-HSA-983169 Class I MHC mediated antigen processing & presentation 0.821121 0.086
R-HSA-391251 Protein folding 0.825783 0.083
R-HSA-9772573 Late SARS-CoV-2 Infection Events 0.825783 0.083
R-HSA-9837999 Mitochondrial protein degradation 0.831670 0.080
R-HSA-1474290 Collagen formation 0.831670 0.080
R-HSA-9824446 Viral Infection Pathways 0.831696 0.080
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 0.834538 0.079
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 0.834538 0.079
R-HSA-72689 Formation of a pool of free 40S subunits 0.837358 0.077
R-HSA-72764 Eukaryotic Translation Termination 0.837358 0.077
R-HSA-1643685 Disease 0.837730 0.077
R-HSA-9909648 Regulation of PD-L1(CD274) expression 0.838374 0.077
R-HSA-5607764 CLEC7A (Dectin-1) signaling 0.840130 0.076
R-HSA-1296071 Potassium Channels 0.840130 0.076
R-HSA-8957322 Metabolism of steroids 0.840194 0.076
R-HSA-157579 Telomere Maintenance 0.842856 0.074
R-HSA-8878159 Transcriptional regulation by RUNX3 0.842856 0.074
R-HSA-112316 Neuronal System 0.842950 0.074
R-HSA-382556 ABC-family proteins mediated transport 0.850756 0.070
R-HSA-5610787 Hedgehog 'off' state 0.850756 0.070
R-HSA-2408557 Selenocysteine synthesis 0.853301 0.069
R-HSA-9009391 Extra-nuclear estrogen signaling 0.853301 0.069
R-HSA-9842860 Regulation of endogenous retroelements 0.855802 0.068
R-HSA-2559580 Oxidative Stress Induced Senescence 0.855802 0.068
R-HSA-192823 Viral mRNA Translation 0.858261 0.066
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 0.860678 0.065
R-HSA-111885 Opioid Signalling 0.860678 0.065
R-HSA-416476 G alpha (q) signalling events 0.864460 0.063
R-HSA-69239 Synthesis of DNA 0.869942 0.061
R-HSA-5663205 Infectious disease 0.870918 0.060
R-HSA-69002 DNA Replication Pre-Initiation 0.874342 0.058
R-HSA-72766 Translation 0.884314 0.053
R-HSA-5628897 TP53 Regulates Metabolic Genes 0.888604 0.051
R-HSA-389948 Co-inhibition by PD-1 0.889063 0.051
R-HSA-2029485 Role of phospholipids in phagocytosis 0.890505 0.050
R-HSA-948021 Transport to the Golgi and subsequent modification 0.892054 0.050
R-HSA-1483206 Glycerophospholipid biosynthesis 0.893521 0.049
R-HSA-1592230 Mitochondrial biogenesis 0.894211 0.049
R-HSA-2980736 Peptide hormone metabolism 0.894211 0.049
R-HSA-9759194 Nuclear events mediated by NFE2L2 0.901253 0.045
R-HSA-2132295 MHC class II antigen presentation 0.904596 0.044
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 0.909401 0.041
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 0.909401 0.041
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 0.909401 0.041
R-HSA-69206 G1/S Transition 0.909401 0.041
R-HSA-73857 RNA Polymerase II Transcription 0.911509 0.040
R-HSA-8951664 Neddylation 0.918107 0.037
R-HSA-1474165 Reproduction 0.918300 0.037
R-HSA-5576891 Cardiac conduction 0.919696 0.036
R-HSA-9824439 Bacterial Infection Pathways 0.921866 0.035
R-HSA-168249 Innate Immune System 0.928421 0.032
R-HSA-6807070 PTEN Regulation 0.931237 0.031
R-HSA-418594 G alpha (i) signalling events 0.935493 0.029
R-HSA-2871837 FCERI mediated NF-kB activation 0.937997 0.028
R-HSA-453279 Mitotic G1 phase and G1/S transition 0.940100 0.027
R-HSA-2187338 Visual phototransduction 0.941125 0.026
R-HSA-9856651 MITF-M-dependent gene expression 0.944095 0.025
R-HSA-9755511 KEAP1-NFE2L2 pathway 0.945052 0.025
R-HSA-1428517 Aerobic respiration and respiratory electron transport 0.946865 0.024
R-HSA-69306 DNA Replication 0.946916 0.024
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 0.947824 0.023
R-HSA-388841 Regulation of T cell activation by CD28 family 0.950072 0.022
R-HSA-9711097 Cellular response to starvation 0.951306 0.022
R-HSA-597592 Post-translational protein modification 0.952108 0.021
R-HSA-877300 Interferon gamma signaling 0.952139 0.021
R-HSA-9006936 Signaling by TGFB family members 0.952959 0.021
R-HSA-9734767 Developmental Cell Lineages 0.954846 0.020
R-HSA-1280218 Adaptive Immune System 0.955690 0.020
R-HSA-2408522 Selenoamino acid metabolism 0.956099 0.019
R-HSA-9711123 Cellular response to chemical stress 0.957987 0.019
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 0.961100 0.017
R-HSA-418555 G alpha (s) signalling events 0.961766 0.017
R-HSA-5621481 C-type lectin receptors (CLRs) 0.961766 0.017
R-HSA-611105 Respiratory electron transport 0.966123 0.015
R-HSA-2559583 Cellular Senescence 0.967275 0.014
R-HSA-3700989 Transcriptional Regulation by TP53 0.967323 0.014
R-HSA-8868773 rRNA processing in the nucleus and cytosol 0.971503 0.013
R-HSA-1483257 Phospholipid metabolism 0.971646 0.012
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 0.973620 0.012
R-HSA-428157 Sphingolipid metabolism 0.977245 0.010
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 0.978019 0.010
R-HSA-9640148 Infection with Enterobacteria 0.978019 0.010
R-HSA-112315 Transmission across Chemical Synapses 0.981260 0.008
R-HSA-392499 Metabolism of proteins 0.981807 0.008
R-HSA-388396 GPCR downstream signalling 0.983639 0.007
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell 0.986234 0.006
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 0.986470 0.006
R-HSA-72312 rRNA processing 0.986932 0.006
R-HSA-15869 Metabolism of nucleotides 0.987808 0.005
R-HSA-202733 Cell surface interactions at the vascular wall 0.988018 0.005
R-HSA-156580 Phase II - Conjugation of compounds 0.988427 0.005
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 0.988435 0.005
R-HSA-372790 Signaling by GPCR 0.993487 0.003
R-HSA-425407 SLC-mediated transmembrane transport 0.993982 0.003
R-HSA-8978868 Fatty acid metabolism 0.994841 0.002
R-HSA-446203 Asparagine N-linked glycosylation 0.995909 0.002
R-HSA-1474244 Extracellular matrix organization 0.997667 0.001
R-HSA-500792 GPCR ligand binding 0.998284 0.001
R-HSA-196854 Metabolism of vitamins and cofactors 0.998689 0.001
R-HSA-71291 Metabolism of amino acids and derivatives 0.998881 0.000
R-HSA-211859 Biological oxidations 0.999165 0.000
R-HSA-5668914 Diseases of metabolism 0.999573 0.000
R-HSA-556833 Metabolism of lipids 0.999925 0.000
R-HSA-382551 Transport of small molecules 0.999996 0.000
R-HSA-9709957 Sensory Perception 1.000000 0.000
R-HSA-1430728 Metabolism 1.000000 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
HIPK2HIPK2 0.761 0.261 1 0.862
HIPK4HIPK4 0.760 0.216 1 0.844
CDK19CDK19 0.760 0.256 1 0.866
CLK3CLK3 0.760 0.173 1 0.865
CDK18CDK18 0.758 0.263 1 0.869
CDK8CDK8 0.757 0.249 1 0.876
SRPK1SRPK1 0.757 0.139 -3 0.475
DYRK2DYRK2 0.756 0.254 1 0.892
PRKD1PRKD1 0.755 0.149 -3 0.570
KISKIS 0.754 0.197 1 0.899
JNK2JNK2 0.754 0.298 1 0.870
CDK7CDK7 0.752 0.224 1 0.895
CDK5CDK5 0.750 0.253 1 0.901
P38GP38G 0.750 0.270 1 0.835
ERK5ERK5 0.749 0.174 1 0.889
JNK3JNK3 0.749 0.288 1 0.879
P38BP38B 0.749 0.266 1 0.894
CDK13CDK13 0.749 0.240 1 0.881
HIPK1HIPK1 0.748 0.237 1 0.896
CDK3CDK3 0.747 0.238 1 0.852
P38DP38D 0.746 0.271 1 0.851
P38AP38A 0.745 0.263 1 0.916
ERK1ERK1 0.745 0.243 1 0.889
CDK9CDK9 0.744 0.251 1 0.884
CLK2CLK2 0.744 0.149 -3 0.454
HIPK3HIPK3 0.744 0.264 1 0.877
CDK12CDK12 0.744 0.237 1 0.866
DYRK4DYRK4 0.744 0.248 1 0.876
CDK1CDK1 0.743 0.219 1 0.876
NLKNLK 0.743 0.187 1 0.877
CDKL5CDKL5 0.742 0.076 -3 0.488
COTCOT 0.742 -0.028 2 0.857
CDK17CDK17 0.742 0.234 1 0.835
SRPK2SRPK2 0.740 0.079 -3 0.404
CLK1CLK1 0.740 0.147 -3 0.449
MTORMTOR 0.739 0.046 1 0.728
PRKD2PRKD2 0.738 0.033 -3 0.500
CDC7CDC7 0.738 0.021 1 0.705
DYRK1ADYRK1A 0.738 0.191 1 0.884
PIM3PIM3 0.738 -0.002 -3 0.510
MAKMAK 0.737 0.174 -2 0.576
CDK16CDK16 0.736 0.238 1 0.844
DYRK1BDYRK1B 0.736 0.217 1 0.878
PRPKPRPK 0.735 0.052 -1 0.397
ICKICK 0.734 0.095 -3 0.522
CLK4CLK4 0.733 0.101 -3 0.451
MOSMOS 0.732 0.009 1 0.746
SKMLCKSKMLCK 0.732 0.058 -2 0.682
CDKL1CDKL1 0.732 0.019 -3 0.483
PRP4PRP4 0.731 0.165 -3 0.551
NDR2NDR2 0.730 -0.042 -3 0.517
SRPK3SRPK3 0.729 0.067 -3 0.431
NEK6NEK6 0.729 0.034 -2 0.642
AURCAURC 0.728 0.006 -2 0.477
NUAK2NUAK2 0.728 0.044 -3 0.503
RSK2RSK2 0.728 -0.008 -3 0.469
MARK4MARK4 0.728 0.069 4 0.827
IKKBIKKB 0.728 -0.081 -2 0.573
CDK2CDK2 0.727 0.168 1 0.879
ATRATR 0.726 0.031 1 0.700
DYRK3DYRK3 0.726 0.147 1 0.878
MAPKAPK3MAPKAPK3 0.726 0.008 -3 0.503
CDK10CDK10 0.725 0.194 1 0.881
PIM1PIM1 0.725 -0.003 -3 0.466
ULK2ULK2 0.725 -0.016 2 0.784
CDK14CDK14 0.725 0.199 1 0.882
CHAK2CHAK2 0.725 0.005 -1 0.354
JNK1JNK1 0.725 0.232 1 0.856
RSK3RSK3 0.725 -0.004 -3 0.476
TSSK1TSSK1 0.724 0.074 -3 0.548
DSTYKDSTYK 0.724 -0.027 2 0.877
P90RSKP90RSK 0.724 -0.014 -3 0.477
WNK1WNK1 0.723 0.033 -2 0.706
PDHK4PDHK4 0.723 -0.091 1 0.712
TSSK2TSSK2 0.723 0.097 -5 0.795
CAMK1BCAMK1B 0.723 -0.021 -3 0.512
MAPKAPK2MAPKAPK2 0.723 -0.010 -3 0.460
IKKAIKKA 0.723 -0.045 -2 0.572
TBK1TBK1 0.723 -0.047 1 0.579
ERK2ERK2 0.722 0.186 1 0.884
CAMK2DCAMK2D 0.722 0.013 -3 0.522
BMPR2BMPR2 0.721 -0.109 -2 0.647
MNK2MNK2 0.721 0.016 -2 0.605
AMPKA1AMPKA1 0.721 0.013 -3 0.528
PDHK1PDHK1 0.721 -0.045 1 0.689
IKKEIKKE 0.720 -0.058 1 0.571
PRKD3PRKD3 0.720 0.018 -3 0.480
RAF1RAF1 0.719 -0.105 1 0.679
BMPR1BBMPR1B 0.719 0.030 1 0.683
AMPKA2AMPKA2 0.719 0.018 -3 0.502
CDK6CDK6 0.719 0.211 1 0.875
HUNKHUNK 0.719 0.048 2 0.817
NDR1NDR1 0.719 -0.062 -3 0.504
MOKMOK 0.718 0.148 1 0.888
GCN2GCN2 0.718 -0.123 2 0.803
CAMLCKCAMLCK 0.718 -0.008 -2 0.638
QSKQSK 0.718 0.035 4 0.805
MLK2MLK2 0.718 0.021 2 0.828
MST4MST4 0.717 -0.038 2 0.843
PKACBPKACB 0.717 -0.011 -2 0.491
PKN3PKN3 0.717 -0.044 -3 0.501
NEK7NEK7 0.717 -0.057 -3 0.509
NEK9NEK9 0.717 0.010 2 0.843
NIKNIK 0.716 -0.033 -3 0.527
DAPK2DAPK2 0.716 -0.006 -3 0.523
PKCBPKCB 0.716 0.023 2 0.739
PAK6PAK6 0.716 0.026 -2 0.524
GRK1GRK1 0.716 -0.060 -2 0.565
ULK1ULK1 0.716 -0.036 -3 0.503
CDK4CDK4 0.716 0.210 1 0.859
GRK5GRK5 0.715 -0.115 -3 0.501
CAMK2GCAMK2G 0.715 -0.071 2 0.796
PKN2PKN2 0.715 -0.030 -3 0.511
NIM1NIM1 0.715 0.002 3 0.739
PKCDPKCD 0.715 -0.021 2 0.778
PKACGPKACG 0.715 -0.050 -2 0.538
PAK1PAK1 0.714 -0.012 -2 0.592
AKT2AKT2 0.714 0.004 -3 0.411
BCKDKBCKDK 0.714 -0.095 -1 0.351
LATS2LATS2 0.714 -0.053 -5 0.666
PAK3PAK3 0.714 -0.009 -2 0.595
SMG1SMG1 0.714 0.004 1 0.653
P70S6KBP70S6KB 0.713 -0.045 -3 0.466
SGK3SGK3 0.713 0.016 -3 0.480
IRE1IRE1 0.713 0.004 1 0.655
MPSK1MPSK1 0.713 0.106 1 0.728
FAM20CFAM20C 0.712 0.020 2 0.597
NEK2NEK2 0.712 0.054 2 0.822
TGFBR2TGFBR2 0.711 -0.098 -2 0.545
MASTLMASTL 0.711 -0.090 -2 0.609
MLK1MLK1 0.711 -0.091 2 0.807
PKG2PKG2 0.710 -0.021 -2 0.494
BRSK1BRSK1 0.710 0.015 -3 0.489
CAMK2ACAMK2A 0.710 -0.013 2 0.784
SIKSIK 0.710 -0.001 -3 0.448
MSK2MSK2 0.709 -0.045 -3 0.467
MARK3MARK3 0.709 0.039 4 0.756
PKCZPKCZ 0.709 -0.006 2 0.781
ERK7ERK7 0.708 0.098 2 0.536
RSK4RSK4 0.708 -0.040 -3 0.438
RIPK3RIPK3 0.708 -0.106 3 0.705
NUAK1NUAK1 0.708 -0.022 -3 0.462
PRKXPRKX 0.708 -0.035 -3 0.401
MSK1MSK1 0.708 -0.028 -3 0.468
MLK3MLK3 0.708 -0.035 2 0.743
DNAPKDNAPK 0.707 0.024 1 0.580
MELKMELK 0.707 -0.035 -3 0.494
MNK1MNK1 0.707 -0.026 -2 0.606
TGFBR1TGFBR1 0.707 -0.023 -2 0.582
PKCAPKCA 0.707 -0.021 2 0.724
PIM2PIM2 0.705 -0.017 -3 0.443
PKACAPKACA 0.704 -0.019 -2 0.457
GSK3AGSK3A 0.704 0.083 4 0.457
VRK2VRK2 0.704 0.027 1 0.757
SSTKSSTK 0.704 0.078 4 0.790
QIKQIK 0.704 -0.044 -3 0.496
ATMATM 0.704 -0.055 1 0.634
BRSK2BRSK2 0.704 -0.007 -3 0.502
MARK2MARK2 0.704 0.025 4 0.730
GRK7GRK7 0.703 -0.047 1 0.653
GRK6GRK6 0.703 -0.106 1 0.684
PKRPKR 0.703 -0.034 1 0.696
PKCGPKCG 0.703 -0.042 2 0.732
ALK4ALK4 0.703 -0.048 -2 0.606
TLK2TLK2 0.703 -0.006 1 0.625
LATS1LATS1 0.703 -0.058 -3 0.522
DCAMKL1DCAMKL1 0.703 -0.007 -3 0.494
CAMK2BCAMK2B 0.703 -0.055 2 0.767
CHK1CHK1 0.702 -0.041 -3 0.504
PHKG1PHKG1 0.702 -0.050 -3 0.504
AURBAURB 0.702 -0.047 -2 0.467
PINK1PINK1 0.702 0.009 1 0.794
CK1ECK1E 0.702 -0.034 -3 0.300
TTBK2TTBK2 0.702 -0.089 2 0.737
WNK3WNK3 0.702 -0.169 1 0.649
GRK4GRK4 0.701 -0.143 -2 0.591
YSK4YSK4 0.700 -0.065 1 0.614
ANKRD3ANKRD3 0.699 -0.134 1 0.701
MAPKAPK5MAPKAPK5 0.699 -0.051 -3 0.438
DLKDLK 0.699 -0.189 1 0.673
AKT3AKT3 0.699 -0.002 -3 0.394
CHAK1CHAK1 0.698 -0.059 2 0.790
PKCHPKCH 0.698 -0.038 2 0.718
RIPK1RIPK1 0.697 -0.170 1 0.654
MEK1MEK1 0.697 -0.066 2 0.845
AKT1AKT1 0.697 -0.026 -3 0.429
MYLK4MYLK4 0.697 -0.051 -2 0.580
ACVR2BACVR2B 0.697 -0.067 -2 0.568
LKB1LKB1 0.697 0.075 -3 0.533
NEK5NEK5 0.697 0.021 1 0.680
IRE2IRE2 0.696 -0.053 2 0.722
SBKSBK 0.696 0.021 -3 0.341
BUB1BUB1 0.696 0.068 -5 0.738
CK1G1CK1G1 0.696 -0.027 -3 0.291
MLK4MLK4 0.696 -0.081 2 0.721
GSK3BGSK3B 0.695 0.045 4 0.450
ACVR2AACVR2A 0.695 -0.080 -2 0.550
PAK2PAK2 0.694 -0.079 -2 0.567
MST3MST3 0.694 -0.001 2 0.835
CAMK4CAMK4 0.694 -0.137 -3 0.478
AURAAURA 0.694 -0.058 -2 0.436
ALK2ALK2 0.694 -0.071 -2 0.571
MARK1MARK1 0.694 -0.016 4 0.776
PKCTPKCT 0.694 -0.022 2 0.728
SGK1SGK1 0.693 -0.005 -3 0.367
WNK4WNK4 0.693 -0.015 -2 0.703
PAK5PAK5 0.692 -0.035 -2 0.463
PLK1PLK1 0.691 -0.127 -2 0.547
BRAFBRAF 0.691 -0.033 -4 0.764
GRK2GRK2 0.691 -0.072 -2 0.522
CK1DCK1D 0.691 -0.051 -3 0.270
PBKPBK 0.690 0.078 1 0.735
PAK4PAK4 0.690 -0.019 -2 0.459
TAO3TAO3 0.690 -0.051 1 0.656
MEKK2MEKK2 0.690 -0.041 2 0.810
BMPR1ABMPR1A 0.689 -0.049 1 0.652
IRAK4IRAK4 0.689 -0.052 1 0.647
TNIKTNIK 0.689 0.059 3 0.850
CAMKK2CAMKK2 0.688 0.005 -2 0.561
PKCIPKCI 0.688 -0.026 2 0.741
PLK4PLK4 0.688 -0.075 2 0.622
PERKPERK 0.688 -0.105 -2 0.586
MEKK1MEKK1 0.688 -0.083 1 0.655
MEKK6MEKK6 0.688 0.082 1 0.658
HRIHRI 0.687 -0.109 -2 0.615
MEK5MEK5 0.687 -0.103 2 0.825
P70S6KP70S6K 0.687 -0.064 -3 0.413
CK1A2CK1A2 0.686 -0.053 -3 0.266
CAMKK1CAMKK1 0.686 -0.045 -2 0.558
HGKHGK 0.686 0.036 3 0.841
PKCEPKCE 0.686 -0.019 2 0.717
PASKPASK 0.685 -0.061 -3 0.520
DRAK1DRAK1 0.685 -0.103 1 0.626
PLK3PLK3 0.685 -0.110 2 0.755
ZAKZAK 0.685 -0.104 1 0.615
SNRKSNRK 0.684 -0.105 2 0.662
DCAMKL2DCAMKL2 0.684 -0.054 -3 0.493
TLK1TLK1 0.684 -0.065 -2 0.614
PKN1PKN1 0.684 -0.023 -3 0.436
GAKGAK 0.683 -0.005 1 0.776
PDK1PDK1 0.683 -0.017 1 0.652
CAMK1DCAMK1D 0.683 -0.060 -3 0.412
NEK4NEK4 0.683 0.014 1 0.637
CK2A2CK2A2 0.683 -0.028 1 0.599
CAMK1GCAMK1G 0.682 -0.090 -3 0.436
PHKG2PHKG2 0.682 -0.070 -3 0.474
SMMLCKSMMLCK 0.681 -0.070 -3 0.486
GRK3GRK3 0.681 -0.076 -2 0.486
DAPK3DAPK3 0.681 -0.044 -3 0.478
KHS1KHS1 0.680 0.029 1 0.634
CHK2CHK2 0.680 -0.037 -3 0.386
NEK1NEK1 0.680 0.025 1 0.645
TAO2TAO2 0.680 -0.059 2 0.840
MINKMINK 0.680 -0.005 1 0.637
MAP3K15MAP3K15 0.680 0.020 1 0.611
HPK1HPK1 0.680 -0.014 1 0.648
GCKGCK 0.679 -0.050 1 0.660
NEK11NEK11 0.679 -0.065 1 0.646
EEF2KEEF2K 0.678 0.007 3 0.814
MEKK3MEKK3 0.677 -0.178 1 0.657
LRRK2LRRK2 0.676 -0.045 2 0.838
MRCKBMRCKB 0.676 -0.047 -3 0.435
LOKLOK 0.676 -0.047 -2 0.576
CAMK1ACAMK1A 0.676 -0.042 -3 0.404
ROCK2ROCK2 0.676 -0.038 -3 0.481
MST2MST2 0.675 -0.084 1 0.658
IRAK1IRAK1 0.675 -0.136 -1 0.315
KHS2KHS2 0.675 -0.002 1 0.650
PKG1PKG1 0.675 -0.047 -2 0.440
HASPINHASPIN 0.674 -0.003 -1 0.282
DAPK1DAPK1 0.674 -0.047 -3 0.462
CK2A1CK2A1 0.672 -0.032 1 0.577
TAK1TAK1 0.672 -0.085 1 0.652
NEK3NEK3 0.672 -0.008 1 0.615
BIKEBIKE 0.671 0.063 1 0.720
NEK8NEK8 0.670 -0.150 2 0.806
YSK1YSK1 0.670 -0.021 2 0.814
VRK1VRK1 0.669 -0.063 2 0.817
AAK1AAK1 0.668 0.096 1 0.668
TTBK1TTBK1 0.668 -0.135 2 0.646
DMPK1DMPK1 0.668 -0.029 -3 0.447
SLKSLK 0.667 -0.102 -2 0.529
MYO3BMYO3B 0.667 0.025 2 0.824
CRIKCRIK 0.666 -0.031 -3 0.436
MEK2MEK2 0.665 -0.073 2 0.822
PDHK3_TYRPDHK3_TYR 0.665 0.093 4 0.888
CK1ACK1A 0.664 -0.047 -3 0.207
MRCKAMRCKA 0.664 -0.088 -3 0.437
STK33STK33 0.663 -0.089 2 0.621
OSR1OSR1 0.662 -0.057 2 0.809
PLK2PLK2 0.661 -0.092 -3 0.443
MST1MST1 0.661 -0.129 1 0.634
ROCK1ROCK1 0.660 -0.056 -3 0.447
LIMK2_TYRLIMK2_TYR 0.659 0.085 -3 0.560
PKMYT1_TYRPKMYT1_TYR 0.659 0.094 3 0.811
ASK1ASK1 0.656 -0.006 1 0.597
MAP2K4_TYRMAP2K4_TYR 0.655 -0.011 -1 0.388
TAO1TAO1 0.654 -0.058 1 0.575
TESK1_TYRTESK1_TYR 0.654 -0.038 3 0.844
MYO3AMYO3A 0.654 -0.033 1 0.629
MAP2K6_TYRMAP2K6_TYR 0.652 -0.026 -1 0.386
TTKTTK 0.651 -0.098 -2 0.557
TNNI3K_TYRTNNI3K_TYR 0.649 0.115 1 0.689
MAP2K7_TYRMAP2K7_TYR 0.648 -0.129 2 0.846
RIPK2RIPK2 0.647 -0.205 1 0.578
EPHA6EPHA6 0.647 -0.005 -1 0.349
BMPR2_TYRBMPR2_TYR 0.647 -0.084 -1 0.356
PDHK4_TYRPDHK4_TYR 0.646 -0.124 2 0.851
ABL2ABL2 0.645 -0.015 -1 0.338
LIMK1_TYRLIMK1_TYR 0.645 -0.043 2 0.845
PDHK1_TYRPDHK1_TYR 0.645 -0.100 -1 0.365
ABL1ABL1 0.644 -0.018 -1 0.339
EPHB4EPHB4 0.643 -0.055 -1 0.334
TXKTXK 0.641 -0.045 1 0.707
YANK3YANK3 0.641 -0.066 2 0.406
ROS1ROS1 0.641 -0.038 3 0.728
PINK1_TYRPINK1_TYR 0.641 -0.163 1 0.707
TYRO3TYRO3 0.640 -0.068 3 0.754
JAK2JAK2 0.639 -0.039 1 0.652
RETRET 0.639 -0.111 1 0.653
ALPHAK3ALPHAK3 0.639 -0.114 -1 0.327
FGRFGR 0.639 -0.064 1 0.737
TNK2TNK2 0.638 -0.014 3 0.710
TYK2TYK2 0.638 -0.082 1 0.646
LCKLCK 0.637 -0.049 -1 0.341
CSF1RCSF1R 0.637 -0.055 3 0.746
DDR1DDR1 0.637 -0.037 4 0.798
BLKBLK 0.636 -0.031 -1 0.333
STLK3STLK3 0.636 -0.113 1 0.584
JAK1JAK1 0.635 0.011 1 0.590
FERFER 0.635 -0.102 1 0.728
YES1YES1 0.635 -0.087 -1 0.349
HCKHCK 0.635 -0.081 -1 0.339
MST1RMST1R 0.635 -0.123 3 0.765
TNK1TNK1 0.634 -0.032 3 0.740
ITKITK 0.633 -0.089 -1 0.320
SRMSSRMS 0.632 -0.090 1 0.701
MERTKMERTK 0.630 -0.066 3 0.720
BMXBMX 0.630 -0.081 -1 0.281
JAK3JAK3 0.629 -0.113 1 0.629
NEK10_TYRNEK10_TYR 0.629 -0.059 1 0.536
EPHB3EPHB3 0.628 -0.102 -1 0.330
CK1G3CK1G3 0.628 -0.083 -3 0.173
EPHB1EPHB1 0.628 -0.110 1 0.696
EPHA4EPHA4 0.627 -0.090 2 0.747
AXLAXL 0.626 -0.098 3 0.722
INSRRINSRR 0.626 -0.111 3 0.696
EPHB2EPHB2 0.625 -0.114 -1 0.318
KITKIT 0.625 -0.112 3 0.746
WEE1_TYRWEE1_TYR 0.624 -0.098 -1 0.314
FYNFYN 0.624 -0.083 -1 0.321
DDR2DDR2 0.623 -0.007 3 0.681
TECTEC 0.623 -0.119 -1 0.292
FGFR2FGFR2 0.623 -0.121 3 0.743
PTK6PTK6 0.623 -0.127 -1 0.316
PDGFRBPDGFRB 0.622 -0.150 3 0.757
PTK2BPTK2B 0.622 -0.049 -1 0.342
METMET 0.622 -0.108 3 0.736
KDRKDR 0.621 -0.119 3 0.710
FGFR1FGFR1 0.621 -0.103 3 0.708
ALKALK 0.621 -0.086 3 0.661
LTKLTK 0.620 -0.091 3 0.686
BTKBTK 0.620 -0.177 -1 0.306
NTRK3NTRK3 0.619 -0.093 -1 0.332
EPHA1EPHA1 0.619 -0.088 3 0.717
TEKTEK 0.618 -0.142 3 0.686
EPHA7EPHA7 0.618 -0.104 2 0.753
LYNLYN 0.616 -0.118 3 0.669
INSRINSR 0.616 -0.092 3 0.680
MATKMATK 0.616 -0.109 -1 0.292
FLT3FLT3 0.615 -0.179 3 0.750
SRCSRC 0.615 -0.094 -1 0.323
PDGFRAPDGFRA 0.613 -0.173 3 0.756
EPHA3EPHA3 0.613 -0.133 2 0.722
FRKFRK 0.613 -0.128 -1 0.335
CSKCSK 0.612 -0.093 2 0.760
NTRK1NTRK1 0.612 -0.180 -1 0.339
FGFR3FGFR3 0.611 -0.142 3 0.714
YANK2YANK2 0.609 -0.077 2 0.421
NTRK2NTRK2 0.609 -0.175 3 0.689
FLT1FLT1 0.609 -0.182 -1 0.315
ERBB2ERBB2 0.607 -0.174 1 0.605
PTK2PTK2 0.607 -0.090 -1 0.297
EPHA8EPHA8 0.607 -0.130 -1 0.299
CK1G2CK1G2 0.607 -0.096 -3 0.234
EGFREGFR 0.606 -0.108 1 0.526
EPHA5EPHA5 0.606 -0.142 2 0.728
FGFR4FGFR4 0.605 -0.116 -1 0.310
SYKSYK 0.604 -0.120 -1 0.299
FLT4FLT4 0.601 -0.193 3 0.699
MUSKMUSK 0.599 -0.118 1 0.525
IGF1RIGF1R 0.598 -0.117 3 0.614
EPHA2EPHA2 0.596 -0.135 -1 0.280
ZAP70ZAP70 0.595 -0.082 -1 0.282
ERBB4ERBB4 0.593 -0.099 1 0.559
FESFES 0.592 -0.124 -1 0.281