Motif 970 (n=1,071)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A2RU30 | TESPA1 | Y358 | ochoa | Protein TESPA1 (Thymocyte-expressed positive selection-associated protein 1) | Required for the development and maturation of T-cells, its function being essential for the late stages of thymocyte development (By similarity). Plays a role in T-cell antigen receptor (TCR)-mediated activation of the ERK and NFAT signaling pathways, possibly by serving as a scaffolding protein that promotes the assembly of the LAT signalosome in thymocytes. May play a role in the regulation of inositol 1,4,5-trisphosphate receptor-mediated Ca(2+) release and mitochondrial Ca(2+) uptake via the mitochondria-associated endoplasmic reticulum membrane (MAM) compartment. {ECO:0000250, ECO:0000269|PubMed:22561606}. |
| A8MPP1 | DDX11L8 | Y202 | ochoa | Putative ATP-dependent DNA helicase DDX11-like protein 8 (EC 5.6.2.-) (DEAD/H box protein 11-like 8) | Putative DNA helicase. {ECO:0000305}. |
| E9PBE3 | None | Y376 | ochoa | BBSome complex member BBS5 | The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly. {ECO:0000256|ARBA:ARBA00054242}. |
| H7C0S8 | None | Y232 | ochoa | Argininosuccinate lyase (Calcitonin gene-related peptide-receptor component protein) (DNA-directed RNA polymerase III subunit RPC9) | Accessory protein for the calcitonin gene-related peptide (CGRP) receptor. It modulates CGRP responsiveness in a variety of tissues. {ECO:0000256|ARBA:ARBA00043924}.; FUNCTION: Catalyzes the reversible cleavage of L-argininosuccinate to fumarate and L-arginine, an intermediate step reaction in the urea cycle mostly providing for hepatic nitrogen detoxification into excretable urea as well as de novo L-arginine synthesis in nonhepatic tissues. Essential regulator of intracellular and extracellular L-arginine pools. As part of citrulline-nitric oxide cycle, forms tissue-specific multiprotein complexes with argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-arginine synthesis while channeling extracellular L-arginine to nitric oxide synthesis pathway. {ECO:0000256|ARBA:ARBA00045522}.; FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. With POLR3H/RPC8 forms a mobile stalk that protrudes from Pol III core and functions primarily in transcription initiation. Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway. {ECO:0000256|ARBA:ARBA00045808}. |
| O00194 | RAB27B | Y122 | ochoa | Ras-related protein Rab-27B (EC 3.6.5.2) (C25KG) | Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion (PubMed:30771381). Plays a role in NTRK2/TRKB axonal anterograde transport by facilitating the association of NTRK2/TRKB with KLC1 (PubMed:21775604). May be involved in targeting uroplakins to urothelial apical membranes (By similarity). {ECO:0000250|UniProtKB:Q8HZJ5, ECO:0000269|PubMed:21775604, ECO:0000269|PubMed:30771381}. |
| O00273 | DFFA | Y27 | ochoa | DNA fragmentation factor subunit alpha (DNA fragmentation factor 45 kDa subunit) (DFF-45) (Inhibitor of CAD) (ICAD) | Inhibitor of the caspase-activated DNase (DFF40). |
| O00308 | WWP2 | Y545 | ochoa | NEDD4-like E3 ubiquitin-protein ligase WWP2 (EC 2.3.2.26) (Atrophin-1-interacting protein 2) (AIP2) (HECT-type E3 ubiquitin transferase WWP2) (WW domain-containing protein 2) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation. {ECO:0000269|PubMed:19274063, ECO:0000269|PubMed:19651900}. |
| O00522 | KRIT1 | Y260 | ochoa | Krev interaction trapped protein 1 (Krev interaction trapped 1) (Cerebral cavernous malformations 1 protein) | Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels. May play a role in the regulation of macroautophagy through the down-regulation of the mTOR pathway (PubMed:26417067). {ECO:0000250|UniProtKB:Q6S5J6, ECO:0000269|PubMed:11741838, ECO:0000269|PubMed:17916086, ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:20616044, ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21633110, ECO:0000269|PubMed:23317506, ECO:0000269|PubMed:26417067}. |
| O00560 | SDCBP | Y50 | ochoa | Syntenin-1 (Melanoma differentiation-associated protein 9) (MDA-9) (Pro-TGF-alpha cytoplasmic domain-interacting protein 18) (TACIP18) (Scaffold protein Pbp1) (Syndecan-binding protein 1) | Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:11498591, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:26539120, ECO:0000303|PubMed:26291527}. |
| O00750 | PIK3C2B | Y228 | ochoa | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (PI3K-C2-beta) (PtdIns-3-kinase C2 subunit beta) (EC 2.7.1.137) (EC 2.7.1.154) (C2-PI3K) (Phosphoinositide 3-kinase-C2-beta) | Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns (PubMed:10805725, PubMed:11533253, PubMed:9830063). Does not phosphorylate PtdIns(4,5)P2 (PubMed:9830063). May be involved in EGF and PDGF signaling cascades (PubMed:10805725). {ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11533253, ECO:0000269|PubMed:9830063}. |
| O14559 | ARHGAP33 | Y406 | psp | Rho GTPase-activating protein 33 (Rho-type GTPase-activating protein 33) (Sorting nexin-26) (Tc10/CDC42 GTPase-activating protein) | May be involved in several stages of intracellular trafficking. Could play an important role in the regulation of glucose transport by insulin. May act as a downstream effector of RHOQ/TC10 in the regulation of insulin-stimulated glucose transport (By similarity). {ECO:0000250}. |
| O14641 | DVL2 | Y275 | psp | Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) | Plays a role in the signal transduction pathways mediated by multiple Wnt genes (PubMed:24616100). Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499, ECO:0000269|PubMed:24616100}. |
| O14744 | PRMT5 | Y304 | psp | Protein arginine N-methyltransferase 5 (PRMT5) (EC 2.1.1.320) (72 kDa ICln-binding protein) (Histone-arginine N-methyltransferase PRMT5) (Jak-binding protein 1) (Shk1 kinase-binding protein 1 homolog) (SKB1 homolog) (SKB1Hs) [Cleaved into: Protein arginine N-methyltransferase 5, N-terminally processed] | Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21081503, PubMed:21258366, PubMed:21917714, PubMed:22269951). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:11747828, PubMed:12411503, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). May methylate the N-terminal region of MBD2 (PubMed:16428440). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity). Methylates histone H3 'Arg-8', which may repress transcription (By similarity). Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21258366, PubMed:21917714). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically methylates NCL (PubMed:21081503). Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (PubMed:19011621). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (By similarity). {ECO:0000250|UniProtKB:Q8CIG8, ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:11152681, ECO:0000269|PubMed:11747828, ECO:0000269|PubMed:12411503, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20421892, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805}. |
| O14874 | BCKDK | Y246 | psp | 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}. |
| O14920 | IKBKB | Y199 | psp | Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK-2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:9346484}. |
| O14939 | PLD2 | Y179 | psp | Phospholipase D2 (PLD 2) (hPLD2) (EC 3.1.4.4) (Choline phosphatase 2) (PLD1C) (Phosphatidylcholine-hydrolyzing phospholipase D2) | Function as phospholipase selective for phosphatidylcholine (PubMed:9582313). May have a role in signal-induced cytoskeletal regulation and/or endocytosis (By similarity). {ECO:0000250|UniProtKB:P97813, ECO:0000269|PubMed:9582313}. |
| O14939 | PLD2 | Y296 | 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}. |
| O15056 | SYNJ2 | Y490 | psp | Synaptojanin-2 (EC 3.1.3.36) (Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 2) | Inositol 5-phosphatase which may be involved in distinct membrane trafficking and signal transduction pathways. May mediate the inhibitory effect of Rac1 on endocytosis. |
| O15231 | ZNF185 | Y581 | ochoa | Zinc finger protein 185 (LIM domain protein ZNF185) (P1-A) | May be involved in the regulation of cellular proliferation and/or differentiation. |
| O15304 | SIVA1 | Y53 | psp | Apoptosis regulatory protein Siva (CD27-binding protein) (CD27BP) | Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits activation of NF-kappa-B and promotes T-cell receptor-mediated apoptosis. {ECO:0000269|PubMed:12011449, ECO:0000269|PubMed:14739602, ECO:0000269|PubMed:15034012, ECO:0000269|PubMed:15958577, ECO:0000269|PubMed:16491128}. |
| O15357 | INPPL1 | Y1135 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (EC 3.1.3.86) (Inositol polyphosphate phosphatase-like protein 1) (INPPL-1) (Protein 51C) (SH2 domain-containing inositol 5'-phosphatase 2) (SH2 domain-containing inositol phosphatase 2) (SHIP-2) | Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:16824732). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:9660833). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (By similarity). Part of a signaling pathway that regulates actin cytoskeleton remodeling (PubMed:11739414, PubMed:12676785). Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation (PubMed:15668240). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956). Regulates cell adhesion and cell spreading (PubMed:12235291). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (PubMed:15735664). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (PubMed:17135240). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (PubMed:12690104). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:11016922). Involved in EGF signaling pathway (PubMed:11349134). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (PubMed:11349134). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (PubMed:11349134). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (PubMed:23273569). {ECO:0000250|UniProtKB:F1PNY0, ECO:0000250|UniProtKB:Q6P549, ECO:0000250|UniProtKB:Q9WVR3, ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12676785, ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15668240, ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:17135240, ECO:0000269|PubMed:21624956, ECO:0000269|PubMed:23273569, ECO:0000269|PubMed:9660833}. |
| O15379 | HDAC3 | Y328 | psp | Histone deacetylase 3 (HD3) (EC 3.5.1.98) (Protein deacetylase HDAC3) (EC 3.5.1.-) (Protein deacylase HDAC3) (EC 3.5.1.-) (RPD3-2) (SMAP45) | Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:21030595, PubMed:21444723, PubMed:23911289, PubMed:25301942, PubMed:28167758, PubMed:28497810, PubMed:32404892, PubMed:22230954). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes, such as N-Cor repressor complex, which activate the histone deacetylase activity (PubMed:23911289, PubMed:22230954). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293, PubMed:35044827). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293). Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290). {ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:22230954, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:32404892, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:38961290}. |
| O15397 | IPO8 | Y598 | ochoa | Importin-8 (Imp8) (Ran-binding protein 8) (RanBP8) | Involved in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, may serve as receptor for nuclear localization signals (NLS) and promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:9214382). In vitro mediates the nuclear import of the signal recognition particle protein SRP19 (PubMed:11682607). May also be involved in cytoplasm-to-nucleus shuttling of a broad spectrum of other cargos, including Argonaute-microRNAs complexes, the JUN protein, RELA/NF-kappa-B p65 subunit, the translation initiation factor EIF4E and a set of receptor-activated mothers against decapentaplegic homolog (SMAD) transcription factors that play a critical role downstream of the large family of transforming growth factor beta and bone morphogenetic protein (BMP) cytokines (Probable). {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9214382, ECO:0000305|PubMed:34010604}. |
| O15492 | RGS16 | Y177 | psp | Regulator of G-protein signaling 16 (RGS16) (A28-RGS14P) (Retinal-specific RGS) (RGS-r) (hRGS-r) (Retinally abundant regulator of G-protein signaling) | Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:11602604, PubMed:18434541). Plays an important role in the phototransduction cascade by regulating the lifetime and effective concentration of activated transducin alpha. May regulate extra and intracellular mitogenic signals (By similarity). {ECO:0000250|UniProtKB:P97428, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:18434541}. |
| O15547 | P2RX6 | Y64 | psp | P2X purinoceptor 6 (P2X6) (ATP receptor) (P2XM) (Purinergic receptor) (Purinergic receptor P2X-like 1) | May act as a modulatory subunit rather than a functional channel. Unlike other P2XRs members, P2RX6 does not seem to form functional homotrimers (PubMed:22378790). P2RX6 requires the presence of P2RX4 or P2RX2 to shuttle it to the plasma membrane where it may form functional heterotrimeric receptors at the plasma membrane (PubMed:22378790). P2RX6 can be translocated to the nucleus and functions as a nuclear regulator of post-transcriptional modifications in neurons (By similarity). {ECO:0000250|UniProtKB:O54803, ECO:0000269|PubMed:22378790}. |
| O43150 | ASAP2 | Y763 | ochoa | Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 (Development and differentiation-enhancing factor 2) (Paxillin-associated protein with ARF GAP activity 3) (PAG3) (Pyk2 C-terminus-associated protein) (PAP) | Activates the small GTPases ARF1, ARF5 and ARF6. Regulates the formation of post-Golgi vesicles and modulates constitutive secretion. Modulates phagocytosis mediated by Fc gamma receptor and ARF6. Modulates PXN recruitment to focal contacts and cell migration. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:10749932, ECO:0000269|PubMed:11304556}. |
| O43463 | SUV39H1 | Y303 | psp | Histone-lysine N-methyltransferase SUV39H1 (EC 2.1.1.355) (Histone H3-K9 methyltransferase 1) (H3-K9-HMTase 1) (Lysine N-methyltransferase 1A) (Position-effect variegation 3-9 homolog) (Suppressor of variegation 3-9 homolog 1) (Su(var)3-9 homolog 1) | Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation. {ECO:0000269|PubMed:14765126, ECO:0000269|PubMed:16449642, ECO:0000269|PubMed:16818776, ECO:0000269|PubMed:16858404, ECO:0000269|PubMed:18004385, ECO:0000269|PubMed:18485871, ECO:0000269|PubMed:30111536}.; FUNCTION: (Microbial infection) Plays a role in defense against mycobacterial infections. Methylates M.tuberculosis HupB on 'Lys-140', probably methylates HupB of M.bovis also. Methylation has an inhibitory effect on mycobacterial growth in the host. Macrophages expressing about 60% SUV39H1 are slightly more susceptible to M.bovis or M.tuberculosis infection. Chaetocin (an inhibitor of this enzyme) increases macrophage survival of M.tuberculosis. This protein inhibits biofilm formation by M.tuberculosis via 'Lys-140' trimethylation. {ECO:0000269|PubMed:29170282}. |
| O43597 | SPRY2 | Y283 | psp | Protein sprouty homolog 2 (Spry-2) | Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity). Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (By similarity). Inhibits CBL/C-CBL-mediated EGFR ubiquitination (PubMed:17974561). {ECO:0000250|UniProtKB:Q9QXV8, ECO:0000269|PubMed:17974561}. |
| O60333 | KIF1B | Y1429 | ochoa | Kinesin-like protein KIF1B (Klp) (EC 5.6.1.3) | Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules. {ECO:0000269|PubMed:16225668}.; FUNCTION: [Isoform 2]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde synaptic vesicle transport along axonal microtubules from the cell body to the presynapse in neuronal cells (By similarity). Functions as a downstream effector in a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells (PubMed:18334619). {ECO:0000250|UniProtKB:Q60575, ECO:0000269|PubMed:18334619}.; FUNCTION: [Isoform 3]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde transport of mitochondria. {ECO:0000269|PubMed:16225668}. |
| O60610 | DIAPH1 | Y424 | ochoa | Protein diaphanous homolog 1 (Diaphanous-related formin-1) (DRF1) | Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (By similarity). {ECO:0000250|UniProtKB:O08808, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24781755, ECO:0000269|PubMed:26912466}. |
| O60658 | PDE8A | Y461 | ochoa | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC 3.1.4.53) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299). {ECO:0000269|PubMed:18983167, ECO:0000269|PubMed:23509299}. |
| O60662 | KLHL41 | Y438 | ochoa | Kelch-like protein 41 (Kel-like protein 23) (Kelch repeat and BTB domain-containing protein 10) (Kelch-related protein 1) (Sarcosin) | Involved in skeletal muscle development and differentiation. Regulates proliferation and differentiation of myoblasts and plays a role in myofibril assembly by promoting lateral fusion of adjacent thin fibrils into mature, wide myofibrils. Required for pseudopod elongation in transformed cells. {ECO:0000250|UniProtKB:A2AUC9}. |
| O60664 | PLIN3 | Y251 | psp | 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}. |
| O60674 | JAK2 | Y813 | psp | Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2) | Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}. |
| O60674 | JAK2 | Y972 | psp | Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2) | Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}. |
| O75167 | PHACTR2 | Y579 | ochoa | Phosphatase and actin regulator 2 | None |
| O75575 | CRCP | Y47 | ochoa | DNA-directed RNA polymerase III subunit RPC9 (RNA polymerase III subunit C9) (Calcitonin gene-related peptide-receptor component protein) (CGRP-RCP) (CGRP-receptor component protein) (CGRPRCP) (HsC17) | DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:20413673, PubMed:33558764, PubMed:34675218). Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. With POLR3H/RPC8 forms a mobile stalk that protrudes from Pol III core and functions primarily in transcription initiation (By similarity) (PubMed:20413673, PubMed:33558764, PubMed:33558766, PubMed:34675218). Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway (PubMed:19609254, PubMed:19631370). {ECO:0000250|UniProtKB:Q9C0Z9, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20413673, ECO:0000269|PubMed:33558764, ECO:0000269|PubMed:33558766, ECO:0000269|PubMed:34675218}.; FUNCTION: Accessory protein for the calcitonin gene-related peptide (CGRP) receptor. It modulates CGRP responsiveness in a variety of tissues. {ECO:0000250|UniProtKB:O35427}. |
| O75665 | OFD1 | Y558 | ochoa | Centriole and centriolar satellite protein OFD1 (Oral-facial-digital syndrome 1 protein) (Protein 71-7A) | Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250|UniProtKB:Q80Z25, ECO:0000269|PubMed:33934390}. |
| O75665 | OFD1 | Y751 | ochoa | Centriole and centriolar satellite protein OFD1 (Oral-facial-digital syndrome 1 protein) (Protein 71-7A) | Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250|UniProtKB:Q80Z25, ECO:0000269|PubMed:33934390}. |
| O75674 | TOM1L1 | Y109 | ochoa | TOM1-like protein 1 (Src-activating and signaling molecule protein) (Target of Myb-like protein 1) | Probable adapter protein involved in signaling pathways. Interacts with the SH2 and SH3 domains of various signaling proteins when it is phosphorylated. May promote FYN activation, possibly by disrupting intramolecular SH3-dependent interactions (By similarity). {ECO:0000250}. |
| O75830 | SERPINI2 | Y184 | ochoa | Serpin I2 (Myoepithelium-derived serine protease inhibitor) (Pancpin) (Pancreas-specific protein TSA2004) (Peptidase inhibitor 14) (PI-14) | None |
| O75874 | IDH1 | Y42 | psp | Isocitrate dehydrogenase [NADP] cytoplasmic (IDH) (IDH1) (EC 1.1.1.42) (Cytosolic NADP-isocitrate dehydrogenase) (IDPc) (NADP(+)-specific ICDH) (Oxalosuccinate decarboxylase) | Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase (PubMed:10521434, PubMed:19935646). Plays a critical role in the generation of NADPH, an important cofactor in many biosynthesis pathways (PubMed:10521434). May act as a corneal epithelial crystallin and may be involved in maintaining corneal epithelial transparency (By similarity). {ECO:0000250|UniProtKB:Q9XSG3, ECO:0000269|PubMed:10521434, ECO:0000269|PubMed:19935646, ECO:0000303|PubMed:10521434}. |
| O75934 | BCAS2 | Y207 | ochoa | Pre-mRNA-splicing factor SPF27 (Breast carcinoma-amplified sequence 2) (DNA amplified in mammary carcinoma 1 protein) (Spliceosome-associated protein SPF 27) | Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR). {ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30705154}. |
| O75955 | FLOT1 | Y223 | ochoa | Flotillin-1 | May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. |
| O94921 | CDK14 | Y146 | ochoa | Cyclin-dependent kinase 14 (EC 2.7.11.22) (Cell division protein kinase 14) (Serine/threonine-protein kinase PFTAIRE-1) (hPFTAIRE1) | Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by mediating the phosphorylation of LRP6 at 'Ser-1490', leading to the activation of the Wnt signaling pathway. Acts as a regulator of cell cycle progression and cell proliferation via its interaction with CCDN3. Phosphorylates RB1 in vitro, however the relevance of such result remains to be confirmed in vivo. May also play a role in meiosis, neuron differentiation and may indirectly act as a negative regulator of insulin-responsive glucose transport. {ECO:0000269|PubMed:16461467, ECO:0000269|PubMed:17517622, ECO:0000269|PubMed:19524571, ECO:0000269|PubMed:20059949}. |
| O94953 | KDM4B | Y200 | ochoa | Lysine-specific demethylase 4B (EC 1.14.11.66) (JmjC domain-containing histone demethylation protein 3B) (Jumonji domain-containing protein 2B) ([histone H3]-trimethyl-L-lysine(9) demethylase 4B) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate (PubMed:16603238, PubMed:28262558). Plays a critical role in the development of the central nervous system (CNS). {ECO:0000250|UniProtKB:Q91VY5, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}. |
| O95171 | SCEL | Y295 | ochoa | Sciellin | May function in the assembly or regulation of proteins in the cornified envelope. The LIM domain may be involved in homotypic or heterotypic associations and may function to localize sciellin to the cornified envelope. |
| O95490 | ADGRL2 | Y1383 | ochoa | Adhesion G protein-coupled receptor L2 (Calcium-independent alpha-latrotoxin receptor 2) (CIRL-2) (Latrophilin homolog 1) (Latrophilin-2) (Lectomedin-1) | Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (By similarity). Following G-protein coupled receptor activation, associates with cell adhesion molecules that are expressed at the surface of adjacent cells to direct synapse specificity. Specifically mediates the establishment of perforant-path synapses on CA1-region pyramidal neurons in the hippocampus. Localizes to postsynaptic spines in excitatory synapses in the S.lacunosum-moleculare and interacts with presynaptic cell adhesion molecules, such as teneurins, promoting synapse formation (By similarity). {ECO:0000250|UniProtKB:Q80TS3, ECO:0000250|UniProtKB:Q8JZZ7}. |
| O95789 | ZMYM6 | Y833 | ochoa | Zinc finger MYM-type protein 6 (Transposon-derived Buster2 transposase-like protein) (Zinc finger protein 258) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| O95865 | DDAH2 | Y207 | psp | Putative hydrolase DDAH2 (EC 3.-.-.-) (DDAHII) (Inactive N(G),N(G)-dimethylarginine dimethylaminohydrolase 2) (DDAH-2) (Inactive dimethylarginine dimethylaminohydrolase 2) (Protein G6a) (S-phase protein) | Putative hydrolase with unknown substrate (Probable). Does not hydrolyze N(G),N(G)-dimethyl-L-arginine (ADMA) which acts as an inhibitor of NOS (PubMed:21493890, PubMed:37296100). In endothelial cells, induces expression of vascular endothelial growth factor (VEGF) via phosphorylation of the transcription factor SP1 by PKA in a process that is independent of NO and NO synthase (By similarity). Similarly, enhances pancreatic insulin secretion through SP1-mediated transcriptional up-regulation of secretagogin/SCGN, an insulin vesicle docking protein (By similarity). Upon viral infection, relocates to mitochondria where it promotes mitochondrial fission through activation of DNM1L leading to the inhibition of innate response activation mediated by MAVS (PubMed:33850055). {ECO:0000250|UniProtKB:Q99LD8, ECO:0000269|PubMed:21493890, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:37296100, ECO:0000305|PubMed:10493931, ECO:0000305|PubMed:21493890, ECO:0000305|PubMed:37296100}. |
| P00519 | ABL1 | Y70 | psp | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P00519 | ABL1 | Y253 | psp | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P00533 | EGFR | Y1092 | ochoa|psp | Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}. |
| P00533 | EGFR | Y1172 | ochoa|psp | Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}. |
| P04075 | ALDOA | Y204 | ochoa | Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) | Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}. |
| P04350 | TUBB4A | Y222 | ochoa | Tubulin beta-4A chain (Tubulin 5 beta) (Tubulin beta-4 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P06241 | FYN | Y213 | ochoa|psp | Tyrosine-protein kinase Fyn (EC 2.7.10.2) (Proto-oncogene Syn) (Proto-oncogene c-Fyn) (Src-like kinase) (SLK) (p59-Fyn) | Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance (PubMed:11536198, PubMed:15489916, PubMed:15557120, PubMed:16387660, PubMed:20100835, PubMed:7568038, PubMed:7822789). Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain (PubMed:15489916). Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions (PubMed:15489916). Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin) (PubMed:17194753). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT (PubMed:14707117, PubMed:15536091). Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage (PubMed:16841086). Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6 (PubMed:14761972, PubMed:18258597, PubMed:19179337). Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein (PubMed:11162638, PubMed:12788081, PubMed:19652227). Involved in reelin signaling by mediating phosphorylation of DAB1 following reelin (RELN)-binding to its receptor (By similarity). Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation (PubMed:22080863). Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation (PubMed:20028775). Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts (PubMed:18056706). CSK maintains LCK and FYN in an inactive form (By similarity). Promotes CD28-induced phosphorylation of VAV1 (PubMed:11005864). In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (By similarity). Can also promote CD244-mediated NK cell activation (PubMed:15713798). {ECO:0000250|UniProtKB:P39688, ECO:0000269|PubMed:11005864, ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11536198, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:14707117, ECO:0000269|PubMed:14761972, ECO:0000269|PubMed:15536091, ECO:0000269|PubMed:15557120, ECO:0000269|PubMed:15713798, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:16841086, ECO:0000269|PubMed:17194753, ECO:0000269|PubMed:18056706, ECO:0000269|PubMed:18258597, ECO:0000269|PubMed:19179337, ECO:0000269|PubMed:19652227, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:7568038, ECO:0000269|PubMed:7822789, ECO:0000303|PubMed:15489916}. |
| P07203 | GPX1 | Y98 | psp | Glutathione peroxidase 1 (GPx-1) (GSHPx-1) (EC 1.11.1.9) (Cellular glutathione peroxidase) (Phospholipid-hydroperoxide glutathione peroxidase GPX1) (EC 1.11.1.12) | Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). In platelets catalyzes the reduction of 12-hydroperoxyeicosatetraenoic acid, the primary product of the arachidonate 12-lipoxygenase pathway (PubMed:11115402). {ECO:0000269|PubMed:11115402, ECO:0000269|PubMed:36608588}. |
| P07437 | TUBB | Y222 | ochoa | Tubulin beta chain (Tubulin beta-5 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P07814 | EPRS1 | Y224 | ochoa | Bifunctional glutamate/proline--tRNA ligase (Bifunctional aminoacyl-tRNA synthetase) (Cell proliferation-inducing gene 32 protein) (Glutamatyl-prolyl-tRNA synthetase) [Includes: Glutamate--tRNA ligase (EC 6.1.1.17) (Glutamyl-tRNA synthetase) (GluRS); Proline--tRNA ligase (EC 6.1.1.15) (Prolyl-tRNA synthetase)] | Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (PubMed:23263184, PubMed:24100331, PubMed:29576217, PubMed:3290852, PubMed:37212275). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3'-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts (PubMed:15479637, PubMed:23071094). Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:28178239, ECO:0000269|PubMed:29576217, ECO:0000269|PubMed:3290852, ECO:0000269|PubMed:37212275}. |
| P07900 | HSP90AA1 | Y61 | ochoa | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| P07947 | YES1 | Y222 | ochoa | Tyrosine-protein kinase Yes (EC 2.7.10.2) (Proto-oncogene c-Yes) (p61-Yes) | Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity (PubMed:26979622). {ECO:0000269|PubMed:11901164, ECO:0000269|PubMed:18479465, ECO:0000269|PubMed:19276087, ECO:0000269|PubMed:21566460, ECO:0000269|PubMed:21713032, ECO:0000269|PubMed:26979622}. |
| P07948 | LYN | Y193 | ochoa | Tyrosine-protein kinase Lyn (EC 2.7.10.2) (Lck/Yes-related novel protein tyrosine kinase) (V-yes-1 Yamaguchi sarcoma viral related oncogene homolog) (p53Lyn) (p56Lyn) | Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration (PubMed:36932076). Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (PubMed:9020138). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:36122175, ECO:0000269|PubMed:36932076, ECO:0000269|PubMed:7687428, ECO:0000269|PubMed:9020138}. |
| P07949 | RET | Y806 | psp | Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment] | Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698). {ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:25242331, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31118272}.; FUNCTION: [Isoform 1]: Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. {ECO:0000269|PubMed:28846099}. |
| P07949 | RET | Y928 | psp | Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment] | Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698). {ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:25242331, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31118272}.; FUNCTION: [Isoform 1]: Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. {ECO:0000269|PubMed:28846099}. |
| P07949 | RET | Y952 | psp | Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment] | Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698). {ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:25242331, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31118272}.; FUNCTION: [Isoform 1]: Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. {ECO:0000269|PubMed:28846099}. |
| P08238 | HSP90AB1 | Y56 | ochoa | Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}. |
| P08559 | PDHA1 | Y289 | ochoa|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}. |
| P08559 | PDHA1 | Y366 | ochoa | 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}. |
| P08559 | PDHA1 | Y369 | ochoa | 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}. |
| P09661 | SNRPA1 | Y117 | 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}. |
| P09769 | FGR | Y208 | ochoa | Tyrosine-protein kinase Fgr (EC 2.7.10.2) (Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog) (Proto-oncogene c-Fgr) (p55-Fgr) (p58-Fgr) (p58c-Fgr) | Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as a negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as a positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity). {ECO:0000250|UniProtKB:P14234, ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}. |
| P09972 | ALDOC | Y204 | ochoa | Fructose-bisphosphate aldolase C (EC 4.1.2.13) (Brain-type aldolase) | None |
| P0DPH7 | TUBA3C | Y224 | ochoa | Tubulin alpha-3C chain (EC 3.6.5.-) (Alpha-tubulin 2) (Alpha-tubulin 3C) (Tubulin alpha-2 chain) [Cleaved into: Detyrosinated tubulin alpha-3C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH8 | TUBA3D | Y224 | ochoa | Tubulin alpha-3D chain (EC 3.6.5.-) (Alpha-tubulin 3D) [Cleaved into: Detyrosinated tubulin alpha-3D chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P10747 | CD28 | Y191 | ochoa|psp | T-cell-specific surface glycoprotein CD28 (TP44) (CD antigen CD28) | Receptor that plays a role in T-cell activation, proliferation, survival and the maintenance of immune homeostasis (PubMed:1650475, PubMed:7568038). Functions not only as an amplifier of TCR signals but delivers unique signals that control intracellular biochemical events that alter the gene expression program of T-cells (PubMed:24665965). Stimulation upon engagement of its cognate ligands CD80 or CD86 increases proliferation and expression of various cytokines in particular IL2 production in both CD4(+) and CD8(+) T-cell subsets (PubMed:1650475, PubMed:35397202). Mechanistically, ligation induces recruitment of protein kinase C-theta/PRKCQ and GRB2 leading to NF-kappa-B activation via both PI3K/Akt-dependent and -independent pathways (PubMed:21964608, PubMed:24665965, PubMed:7568038). In conjunction with TCR/CD3 ligation and CD40L costimulation, enhances the production of IL4 and IL10 in T-cells (PubMed:8617933). {ECO:0000269|PubMed:1650475, ECO:0000269|PubMed:21964608, ECO:0000269|PubMed:24665965, ECO:0000269|PubMed:35397202, ECO:0000269|PubMed:7568038, ECO:0000269|PubMed:8617933}.; FUNCTION: [Isoform 3]: Enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells (PubMed:15067037). {ECO:0000269|PubMed:15067037}. |
| P10912 | GHR | Y534 | psp | Growth hormone receptor (GH receptor) (Somatotropin receptor) [Cleaved into: Growth hormone-binding protein (GH-binding protein) (GHBP) (Serum-binding protein)] | Receptor for pituitary gland growth hormone (GH1) involved in regulating postnatal body growth (PubMed:1549776, PubMed:2825030, PubMed:8943276). On ligand binding, couples to the JAK2/STAT5 pathway (PubMed:1549776, PubMed:15690087, PubMed:2825030, PubMed:8943276). {ECO:0000269|PubMed:1549776, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:2825030, ECO:0000269|PubMed:8943276}.; FUNCTION: [Growth hormone-binding protein]: The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling. {ECO:0000269|PubMed:2825030}.; FUNCTION: [Isoform 2]: Up-regulates the production of the soluble Growth hormone-binding protein form (GHBP) and acts as a negative inhibitor of growth hormone signaling. {ECO:0000269|PubMed:8855247, ECO:0000269|PubMed:9360546}. |
| P11171 | EPB41 | Y222 | ochoa | Protein 4.1 (P4.1) (4.1R) (Band 4.1) (EPB4.1) (Erythrocyte membrane protein band 4.1) | Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}. |
| P11172 | UMPS | Y37 | ochoa | Uridine 5'-monophosphate synthase (UMP synthase) [Includes: Orotate phosphoribosyltransferase (OPRT) (OPRTase) (EC 2.4.2.10); Orotidine 5'-phosphate decarboxylase (ODC) (OMPD) (EC 4.1.1.23) (OMPdecase)] | Bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5'-monophosphate (OMP), and orotidine-5'-monophosphate decarboxylase (ODC), the terminal enzymatic reaction that decarboxylates OMP to uridine monophosphate (UMP). {ECO:0000269|PubMed:18184586, ECO:0000269|PubMed:9042911}. |
| P11217 | PYGM | Y204 | ochoa | Glycogen phosphorylase, muscle form (EC 2.4.1.1) (Myophosphorylase) | Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis. {ECO:0000269|PubMed:8316268}. |
| P11274 | BCR | Y279 | psp | Breakpoint cluster region protein (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-26) | Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:1903516, PubMed:7479768). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:23940119, PubMed:7479768). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119). {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. |
| P11362 | FGFR1 | Y605 | psp | Fibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD antigen CD331) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. {ECO:0000250|UniProtKB:P16092, ECO:0000269|PubMed:10830168, ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19261810, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:20139426, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:8622701, ECO:0000269|PubMed:8663044}. |
| P11362 | FGFR1 | Y677 | psp | Fibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD antigen CD331) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. {ECO:0000250|UniProtKB:P16092, ECO:0000269|PubMed:10830168, ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19261810, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:20139426, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:8622701, ECO:0000269|PubMed:8663044}. |
| P13796 | LCP1 | Y276 | ochoa | Plastin-2 (L-plastin) (LC64P) (Lymphocyte cytosolic protein 1) (LCP-1) | Actin-binding protein (PubMed:16636079, PubMed:17294403, PubMed:28493397). Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28 (PubMed:17294403). Modulates the cell surface expression of IL2RA/CD25 and CD69 (PubMed:17294403). {ECO:0000269|PubMed:16636079, ECO:0000269|PubMed:17294403, ECO:0000269|PubMed:28493397}. |
| P13945 | ADRB3 | Y136 | ochoa | Beta-3 adrenergic receptor (Beta-3 adrenoreceptor) (Beta-3 adrenoceptor) | Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis. |
| P14410 | SI | Y540 | psp | Sucrase-isomaltase, intestinal [Cleaved into: Sucrase (EC 3.2.1.48); Isomaltase (EC 3.2.1.10)] | Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides. {ECO:0000269|PubMed:20356844}. |
| P15391 | CD19 | Y500 | ochoa|psp | B-lymphocyte antigen CD19 (B-lymphocyte surface antigen B4) (Differentiation antigen CD19) (T-cell surface antigen Leu-12) (CD antigen CD19) | Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes (PubMed:29523808). Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:1373518, PubMed:16672701, PubMed:2463100). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:12387743, PubMed:16672701, PubMed:9317126, PubMed:9382888). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:1373518, PubMed:2463100). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:12387743, PubMed:16672701, PubMed:9317126). {ECO:0000250|UniProtKB:P25918, ECO:0000269|PubMed:12387743, ECO:0000269|PubMed:1373518, ECO:0000269|PubMed:16672701, ECO:0000269|PubMed:2463100, ECO:0000269|PubMed:29523808, ECO:0000269|PubMed:9317126, ECO:0000269|PubMed:9382888}. |
| P16333 | NCK1 | Y112 | ochoa | SH2/SH3 adapter protein NCK1 (Cytoplasmic protein NCK1) (NCK adapter protein 1) (Nck-1) (SH2/SH3 adapter protein NCK-alpha) | Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:9430661}. |
| P16410 | CTLA4 | Y201 | psp | Cytotoxic T-lymphocyte protein 4 (Cytotoxic T-lymphocyte-associated antigen 4) (CTLA-4) (CD antigen CD152) | Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28. {ECO:0000269|PubMed:16551244, ECO:0000269|PubMed:1714933}. |
| P16591 | FER | Y199 | ochoa | Tyrosine-protein kinase Fer (EC 2.7.10.2) (Feline encephalitis virus-related kinase FER) (Fujinami poultry sarcoma/Feline sarcoma-related protein Fer) (Proto-oncogene c-Fer) (Tyrosine kinase 3) (p94-Fer) | Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus. {ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:14517306, ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:19738202, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21518868, ECO:0000269|PubMed:22223638, ECO:0000269|PubMed:7623846, ECO:0000269|PubMed:9722593}. |
| P17181 | IFNAR1 | Y466 | psp | Interferon alpha/beta receptor 1 (IFN-R-1) (IFN-alpha/beta receptor 1) (Cytokine receptor class-II member 1) (Cytokine receptor family 2 member 1) (CRF2-1) (Type I interferon receptor 1) | Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:2153461, PubMed:21854986, PubMed:24075985, PubMed:31270247, PubMed:33252644, PubMed:35442418, PubMed:7813427). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:10049744, PubMed:21854986, PubMed:7665574). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (PubMed:21854986, PubMed:32972995, PubMed:7526154, PubMed:7665574, PubMed:7813427). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:19561067, PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427, PubMed:9121453). Can also act independently of IFNAR2: form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity). {ECO:0000250|UniProtKB:P33896, ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:19561067, ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:21854986, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:31270247, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33252644, ECO:0000269|PubMed:35442418, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:9121453}. |
| P19338 | NCL | Y495 | ochoa | Nucleolin (Protein C23) | Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}. |
| P19525 | EIF2AK2 | Y101 | psp | Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) | IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. |
| P20594 | NPR2 | Y808 | psp | Atrial natriuretic peptide receptor 2 (EC 4.6.1.2) (Atrial natriuretic peptide receptor type B) (ANP-B) (ANPR-B) (NPR-B) (Guanylate cyclase B) (GC-B) | Receptor for the C-type natriuretic peptide NPPC/CNP hormone. Has guanylate cyclase activity upon binding of its ligand. May play a role in the regulation of skeletal growth. {ECO:0000269|PubMed:15146390, ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:24001744, ECO:0000269|PubMed:24471569, ECO:0000269|PubMed:26980729}. |
| P21709 | EPHA1 | Y599 | ochoa | Ephrin type-A receptor 1 (hEpha1) (EC 2.7.10.1) (EPH tyrosine kinase) (EPH tyrosine kinase 1) (Erythropoietin-producing hepatoma receptor) (Tyrosine-protein kinase receptor EPH) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217, ECO:0000269|PubMed:20043122}. |
| P21860 | ERBB3 | Y1222 | psp | Receptor tyrosine-protein kinase erbB-3 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-3) (Tyrosine kinase-type cell surface receptor HER3) | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908). {ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:27416908}. |
| P22001 | KCNA3 | Y529 | psp | Potassium voltage-gated channel subfamily A member 3 (HGK5) (HLK3) (HPCN3) (Voltage-gated K(+) channel HuKIII) (Voltage-gated potassium channel subunit Kv1.3) | [Isoform 1]: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. {ECO:0000269|PubMed:36852591}.; FUNCTION: [Isoform 2]: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. {ECO:0000269|PubMed:1373731, ECO:0000269|PubMed:1547020, ECO:0000269|PubMed:1986382, ECO:0000269|PubMed:36852591}.; FUNCTION: [Isoform 3]: Lacks voltage-gated potassium channel activity. {ECO:0000269|PubMed:36852591}. |
| P22455 | FGFR4 | Y390 | psp | Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (CD antigen CD334) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling. {ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:18670643, ECO:0000269|PubMed:20018895, ECO:0000269|PubMed:20683963, ECO:0000269|PubMed:20798051, ECO:0000269|PubMed:20876804, ECO:0000269|PubMed:21653700, ECO:0000269|PubMed:7518429, ECO:0000269|PubMed:7680645, ECO:0000269|PubMed:8663044}. |
| P23528 | CFL1 | Y89 | ochoa | Cofilin-1 (18 kDa phosphoprotein) (p18) (Cofilin, non-muscle isoform) | Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity (PubMed:11812157). In conjunction with the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:15580268). Required for the centralization of the mitotic spindle and symmetric division of zygotes (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization in epithelial cells (PubMed:21834987). Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). Required for neural tube morphogenesis and neural crest cell migration (By similarity). {ECO:0000250|UniProtKB:P18760, ECO:0000269|PubMed:11812157, ECO:0000269|PubMed:15580268, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:23633677}. |
| P23528 | CFL1 | Y140 | ochoa | Cofilin-1 (18 kDa phosphoprotein) (p18) (Cofilin, non-muscle isoform) | Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity (PubMed:11812157). In conjunction with the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:15580268). Required for the centralization of the mitotic spindle and symmetric division of zygotes (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization in epithelial cells (PubMed:21834987). Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). Required for neural tube morphogenesis and neural crest cell migration (By similarity). {ECO:0000250|UniProtKB:P18760, ECO:0000269|PubMed:11812157, ECO:0000269|PubMed:15580268, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:23633677}. |
| P24534 | EEF1B2 | Y182 | ochoa | Elongation factor 1-beta (EF-1-beta) (eEF-1B alpha) | Catalytic subunit of the guanine nucleotide exchange factor (GEF) (eEF1B subcomplex) of the eukaryotic elongation factor 1 complex (eEF1) (By similarity). Stimulates the exchange of GDP for GTP on elongation factor 1A (eEF1A), probably by displacing GDP from the nucleotide binding pocket in eEF1A (By similarity). {ECO:0000250|UniProtKB:P32471}. |
| P24752 | ACAT1 | Y407 | psp | Acetyl-CoA acetyltransferase, mitochondrial (EC 2.3.1.9) (Acetoacetyl-CoA thiolase) (T2) | This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148, PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688, PubMed:7728148, PubMed:9744475). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a major role in ketone body metabolism (PubMed:1715688, PubMed:17371050, PubMed:7728148, PubMed:9744475). {ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:17371050, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. |
| P25090 | FPR2 | Y302 | psp | N-formyl peptide receptor 2 (FMLP-related receptor I) (FMLP-R-I) (Formyl peptide receptor-like 1) (HM63) (Lipoxin A4 receptor) (LXA4 receptor) (RFP) | Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophil chemotactic factors (PubMed:1374236). Binding of FMLP to the receptor causes activation of neutrophils (PubMed:1374236). This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:1374236). The activation of LXA4R could result in an anti-inflammatory outcome counteracting the actions of pro-inflammatory signals such as LTB4 (leukotriene B4) (PubMed:9547339). Receptor for the chemokine-like protein FAM19A5, mediating FAM19A5-stimulated macrophage chemotaxis and the inhibitory effect on TNFSF11/RANKL-induced osteoclast differentiation (By similarity). Acts as a receptor for humanin (PubMed:15465011). {ECO:0000250|UniProtKB:O88536, ECO:0000269|PubMed:1374236, ECO:0000269|PubMed:15465011, ECO:0000269|PubMed:9547339}. |
| P25101 | EDNRA | Y184 | psp | Endothelin-1 receptor (Endothelin receptor type A) (ET-A) (ETA-R) (hET-AR) | Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3. |
| P25101 | EDNRA | Y389 | psp | Endothelin-1 receptor (Endothelin receptor type A) (ET-A) (ETA-R) (hET-AR) | Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3. |
| P25787 | PSMA2 | Y98 | ochoa | Proteasome subunit alpha type-2 (Macropain subunit C3) (Multicatalytic endopeptidase complex subunit C3) (Proteasome component C3) (Proteasome subunit alpha-2) (alpha-2) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P26010 | ITGB7 | Y753 | psp | Integrin beta-7 (Gut homing receptor beta subunit) | Integrin ITGA4/ITGB7 (alpha-4/beta-7) (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT) (Probable). Integrin ITGA4/ITGB7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract (PubMed:10837471, PubMed:14608374). Also interacts with VCAM1 and fibronectin, an extracellular matrix component (Probable). It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin (Probable). Interactions involve the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin (Probable). Integrin ITGAE/ITGB7 (alpha-E/beta-7, HML-1) is a receptor for E-cadherin (PubMed:10837471). {ECO:0000269|PubMed:10837471, ECO:0000269|PubMed:14608374, ECO:0000305|PubMed:12297042}.; FUNCTION: (Microbial infection) Binds to HIV-1 gp120, thereby allowing the virus to enter GALT, which is thought to be the major trigger of AIDS disease. Interaction would involve a tripeptide L-D-I in HIV-1 gp120. {ECO:0000269|PubMed:18264102}. |
| P27348 | YWHAQ | Y48 | ochoa | 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| P27348 | YWHAQ | Y211 | ochoa | 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| P28066 | PSMA5 | Y26 | ochoa | Proteasome subunit alpha type-5 (Macropain zeta chain) (Multicatalytic endopeptidase complex zeta chain) (Proteasome subunit alpha-5) (alpha-5) (Proteasome zeta chain) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P29317 | EPHA2 | Y735 | ochoa|psp | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P29320 | EPHA3 | Y742 | psp | Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}. |
| P29353 | SHC1 | Y315 | ochoa | SHC-transforming protein 1 (SHC-transforming protein 3) (SHC-transforming protein A) (Src homology 2 domain-containing-transforming protein C1) (SH2 domain protein C1) | Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. {ECO:0000250, ECO:0000269|PubMed:14665640}. |
| P29474 | NOS3 | Y657 | psp | Nitric oxide synthase 3 (EC 1.14.13.39) (Constitutive NOS) (cNOS) (EC-NOS) (NOS type III) (NOSIII) (Nitric oxide synthase, endothelial) (Endothelial NOS) (eNOS) | Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. {ECO:0000269|PubMed:1378832}.; FUNCTION: [Isoform eNOS13C]: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1. |
| P29692 | EEF1D | Y238 | 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). |
| P29803 | PDHA2 | Y287 | ochoa | Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial (EC 1.2.4.1) (PDHE1-A type II) | 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:16436377}. |
| P30047 | GCHFR | Y45 | ochoa | GTP cyclohydrolase 1 feedback regulatory protein (GFRP) (GTP cyclohydrolase I feedback regulatory protein) (p35) | Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1. This inhibition is reversed by L-phenylalanine. {ECO:0000269|PubMed:16778797}. |
| P30411 | BDKRB2 | Y332 | psp | B2 bradykinin receptor (B2R) (BK-2 receptor) | Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:1314587, ECO:0000269|PubMed:1329734}. |
| P30530 | AXL | Y698 | psp | Tyrosine-protein kinase receptor UFO (EC 2.7.10.1) (AXL oncogene) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. {ECO:0000269|PubMed:10403904, ECO:0000269|PubMed:11484958, ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:12490074, ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:15733062, ECO:0000269|PubMed:1656220, ECO:0000269|PubMed:18840707}.; FUNCTION: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828, ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:25277499}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22673088}.; FUNCTION: (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes (PubMed:28076778, PubMed:29379210, PubMed:31311882). Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection (PubMed:28076778). Interferon signaling inhibition occurs via an SOCS1-dependent mechanism (PubMed:29379210). {ECO:0000269|PubMed:28076778, ECO:0000269|PubMed:29379210, ECO:0000269|PubMed:31311882}. |
| P30740 | SERPINB1 | Y166 | ochoa | Leukocyte elastase inhibitor (LEI) (Monocyte/neutrophil elastase inhibitor) (EI) (M/NEI) (Peptidase inhibitor 2) (PI-2) (Serpin B1) | Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis (PubMed:30692621). Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3 (PubMed:11747453, PubMed:30692621). Also acts as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity (PubMed:23269243). During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621). When secreted, promotes the proliferation of beta-cells via its protease inhibitory function (PubMed:26701651). {ECO:0000269|PubMed:11747453, ECO:0000269|PubMed:23269243, ECO:0000269|PubMed:26701651, ECO:0000269|PubMed:30692621}. |
| P31645 | SLC6A4 | Y142 | psp | Sodium-dependent serotonin transporter (SERT) (5HT transporter) (5HTT) (Solute carrier family 6 member 4) | Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity). {ECO:0000250|UniProtKB:P31652, ECO:0000250|UniProtKB:Q60857, ECO:0000269|PubMed:10407194, ECO:0000269|PubMed:12869649, ECO:0000269|PubMed:17506858, ECO:0000269|PubMed:18317590, ECO:0000269|PubMed:21730057, ECO:0000269|PubMed:27049939, ECO:0000269|PubMed:27756841, ECO:0000269|PubMed:34851672}. |
| P31749 | AKT1 | Y326 | psp | RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha) | AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:15526160, PubMed:15861136, PubMed:21432781, PubMed:21620960, PubMed:31204173). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960, PubMed:29343641, PubMed:31204173). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF1 (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (PubMed:30504268). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (PubMed:15861136). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (PubMed:31204173). {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10358075, ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941, ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:18507042, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20471940, ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:30504268, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058, ECO:0000269|PubMed:9829964, ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}. |
| P31946 | YWHAB | Y50 | ochoa | 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}. |
| P31946 | YWHAB | Y213 | ochoa | 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}. |
| P31947 | SFN | Y48 | ochoa | 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}. |
| P35372 | OPRM1 | Y338 | psp | Mu-type opioid receptor (M-OR-1) (MOR-1) (Mu opiate receptor) (Mu opioid receptor) (MOP) (hMOP) | Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity). {ECO:0000250|UniProtKB:P33535, ECO:0000269|PubMed:10529478, ECO:0000269|PubMed:12068084, ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, ECO:0000303|PubMed:19300905}.; FUNCTION: [Isoform 12]: Couples to GNAS and is proposed to be involved in excitatory effects. {ECO:0000269|PubMed:20525224}.; FUNCTION: [Isoform 16]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}.; FUNCTION: [Isoform 17]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}. |
| P35579 | MYH9 | Y754 | ochoa | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P35790 | CHKA | Y197 | psp | Choline kinase alpha (CK) (EC 2.7.1.32) (CHETK-alpha) (Ethanolamine kinase) (EK) (EC 2.7.1.82) | Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:17007874, PubMed:19915674, PubMed:23416529, PubMed:34077757). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:17007874, PubMed:19915674). Has higher activity with choline (PubMed:17007874, PubMed:19915674). May contribute to tumor cell growth (PubMed:19915674). {ECO:0000269|PubMed:17007874, ECO:0000269|PubMed:19915674, ECO:0000269|PubMed:23416529, ECO:0000269|PubMed:34077757}.; FUNCTION: [Isoform 1]: This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation (PubMed:34077757). In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets (PubMed:34077757). Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer (PubMed:34077757). Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets (PubMed:34077757). {ECO:0000269|PubMed:34077757}. |
| P35790 | CHKA | Y333 | psp | Choline kinase alpha (CK) (EC 2.7.1.32) (CHETK-alpha) (Ethanolamine kinase) (EK) (EC 2.7.1.82) | Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:17007874, PubMed:19915674, PubMed:23416529, PubMed:34077757). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:17007874, PubMed:19915674). Has higher activity with choline (PubMed:17007874, PubMed:19915674). May contribute to tumor cell growth (PubMed:19915674). {ECO:0000269|PubMed:17007874, ECO:0000269|PubMed:19915674, ECO:0000269|PubMed:23416529, ECO:0000269|PubMed:34077757}.; FUNCTION: [Isoform 1]: This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation (PubMed:34077757). In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets (PubMed:34077757). Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer (PubMed:34077757). Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets (PubMed:34077757). {ECO:0000269|PubMed:34077757}. |
| P35916 | FLT4 | Y1231 | psp | Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}. |
| P36888 | FLT3 | Y793 | psp | Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135) | Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. {ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:16627759, ECO:0000269|PubMed:18490735, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21067588, ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:21516120, ECO:0000269|PubMed:7507245}. |
| P36897 | TGFBR1 | Y182 | ochoa|psp | TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I) | Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis (PubMed:33914044). The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:33914044, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}. |
| P38117 | ETFB | Y192 | ochoa | Electron transfer flavoprotein subunit beta (Beta-ETF) | Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:15159392, PubMed:15975918, PubMed:25416781). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMP molecule that probably has a purely structural role (PubMed:15159392, PubMed:15975918, PubMed:8962055). {ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:15159392, ECO:0000269|PubMed:15975918, ECO:0000269|PubMed:25416781, ECO:0000269|PubMed:7912128, ECO:0000269|PubMed:8962055, ECO:0000303|PubMed:17941859, ECO:0000305}. |
| P38398 | BRCA1 | Y1522 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P38398 | BRCA1 | Y1552 | psp | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P38919 | EIF4A3 | Y54 | ochoa | Eukaryotic initiation factor 4A-III (eIF-4A-III) (eIF4A-III) (EC 3.6.4.13) (ATP-dependent RNA helicase DDX48) (ATP-dependent RNA helicase eIF4A-3) (DEAD box protein 48) (Eukaryotic initiation factor 4A-like NUK-34) (Eukaryotic translation initiation factor 4A isoform 3) (Nuclear matrix protein 265) (NMP 265) (hNMP 265) [Cleaved into: Eukaryotic initiation factor 4A-III, N-terminally processed] | ATP-dependent RNA helicase (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs (PubMed:16170325, PubMed:16209946, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly (PubMed:22203037). Involved in craniofacial development (PubMed:24360810). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:15034551, ECO:0000269|PubMed:16170325, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16314458, ECO:0000269|PubMed:16923391, ECO:0000269|PubMed:16931718, ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:19033377, ECO:0000269|PubMed:19409878, ECO:0000269|PubMed:20479275, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:24360810, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}. |
| P40189 | IL6ST | Y814 | psp | Interleukin-6 receptor subunit beta (IL-6 receptor subunit beta) (IL-6R subunit beta) (IL-6R-beta) (IL-6RB) (CDw130) (Interleukin-6 signal transducer) (Membrane glycoprotein 130) (gp130) (Oncostatin-M receptor subunit alpha) (CD antigen CD130) | Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways (PubMed:19915009, PubMed:2261637, PubMed:23294003). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:19915009, PubMed:23294003, PubMed:25731159). In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL27RA/WSX1 and CNTFR (PubMed:19386761). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity). {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:19915009, ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:28747427, ECO:0000269|PubMed:30309848}.; FUNCTION: [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:30279168). {ECO:0000269|PubMed:11121117, ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:30279168}. |
| P41597 | CCR2 | Y139 | psp | C-C chemokine receptor type 2 (C-C CKR-2) (CC-CKR-2) (CCR-2) (CCR2) (Monocyte chemoattractant protein 1 receptor) (MCP-1-R) (CD antigen CD192) | Key functional receptor for CCL2 but can also bind CCL7, and CCL12 (PubMed:23408426, PubMed:38157855, PubMed:8048929, PubMed:8146186). Also transduces signaling mediated by CCL13 (PubMed:38157855). Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (PubMed:38157855). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B (PubMed:23938203). Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation (By similarity). Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (By similarity). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity). Mediates the recruitment of macrophages and monocytes to the injury site following brain injury (By similarity). {ECO:0000250|UniProtKB:P51683, ECO:0000269|PubMed:23408426, ECO:0000269|PubMed:23938203, ECO:0000269|PubMed:38157855, ECO:0000269|PubMed:8048929, ECO:0000269|PubMed:8146186, ECO:0000305|PubMed:15995708}.; FUNCTION: (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection. {ECO:0000269|PubMed:9789057}. |
| P41743 | PRKCI | Y430 | psp | Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) | Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}. |
| P42226 | STAT6 | Y829 | ochoa | Signal transducer and activator of transcription 6 (IL-4 Stat) | Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling. {ECO:0000269|PubMed:17210636, ECO:0000269|PubMed:36758835, ECO:0000269|PubMed:36884218}. |
| P42684 | ABL2 | Y116 | psp | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P42684 | ABL2 | Y139 | psp | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P42684 | ABL2 | Y299 | psp | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P43403 | ZAP70 | Y474 | psp | 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}. |
| P45974 | USP5 | Y223 | ochoa | Ubiquitin carboxyl-terminal hydrolase 5 (EC 3.4.19.12) (Deubiquitinating enzyme 5) (Isopeptidase T) (Ubiquitin thioesterase 5) (Ubiquitin-specific-processing protease 5) | Deubiquitinating enzyme that participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. Affects thereby important cellular signaling pathways such as NF-kappa-B, Wnt/beta-catenin, and cytokine production by regulating ubiquitin-dependent protein degradation. Participates in the activation of the Wnt signaling pathway by promoting FOXM1 deubiquitination and stabilization that induces the recruitment of beta-catenin to Wnt target gene promoter (PubMed:26912724). Regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains (PubMed:29567855). Promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein (PubMed:37534934). Affects T-cell biology by stabilizing the inhibitory receptor on T-cells PDC1 (PubMed:37208329). Acts as a negative regulator of autophagy by regulating ULK1 at both protein and mRNA levels (PubMed:37607937). Acts also as a negative regulator of type I interferon production by simultaneously removing both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin chains on the transcription factor IRF3 (PubMed:39761299). Modulates the stability of DNA mismatch repair protein MLH1 and counteracts the effect of the ubiquitin ligase UBR4 (PubMed:39032648). Upon activation by insulin, it gets phosphorylated through mTORC1-mediated phosphorylation to enhance YTHDF1 stability by removing 'Lys-11'-linked polyubiquitination (PubMed:39900921). May also deubiquitinate other substrates such as the calcium channel CACNA1H (By similarity). {ECO:0000250|UniProtKB:P56399, ECO:0000269|PubMed:19098288, ECO:0000269|PubMed:26912724, ECO:0000269|PubMed:29567855, ECO:0000269|PubMed:37208329, ECO:0000269|PubMed:37534934, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:39761299, ECO:0000269|PubMed:39900921}. |
| P46937 | YAP1 | Y391 | ochoa|psp | Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog) | Transcriptional regulator with dual roles as a coactivator and corepressor. Critical downstream regulatory target in the Hippo signaling pathway, crucial for organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The Hippo signaling pathway core involves a kinase cascade featuring STK3/MST2 and STK4/MST1, along with its regulatory partner SAV1, which phosphorylates and activates LATS1/2 in complex with their regulatory protein, MOB1. This activation leads to the phosphorylation and inactivation of the YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Phosphorylation of YAP1 by LATS1/2 prevents its nuclear translocation, thereby regulating the expression of its target genes (PubMed:18158288, PubMed:26598551, PubMed:34404733). The transcriptional regulation of gene expression requires TEAD transcription factors and modulates cell growth, anchorage-independent growth, and induction of epithelial-mesenchymal transition (EMT) (PubMed:18579750). Plays a key role in tissue tension and 3D tissue shape by regulating the cortical actomyosin network, acting via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). It also suppresses ciliogenesis by acting as a transcriptional corepressor of TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, regulates TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). Synergizes with WBP2 to enhance PGR activity (PubMed:16772533). {ECO:0000250|UniProtKB:P46938, ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:25778702, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:30447097, ECO:0000269|PubMed:34404733}.; FUNCTION: [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.; FUNCTION: [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}. |
| P48551 | IFNAR2 | Y269 | psp | Interferon alpha/beta receptor 2 (IFN-R-2) (IFN-alpha binding protein) (IFN-alpha/beta receptor 2) (Interferon alpha binding protein) (Type I interferon receptor 2) | Together with IFNAR1, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:10556041, PubMed:21854986, PubMed:26424569, PubMed:28165510, PubMed:32972995, PubMed:7665574, PubMed:7759950, PubMed:8181059, PubMed:8798579, PubMed:8969169). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:10049744, PubMed:17517919, PubMed:21854986, PubMed:26424569, PubMed:28165510, PubMed:32972995, PubMed:7665574, PubMed:7759950, PubMed:8181059, PubMed:8798579, PubMed:8969169). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:10556041, PubMed:11682488, PubMed:12105218, PubMed:21854986, PubMed:32972995). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (STAT1, STAT2 and STAT) (PubMed:11682488, PubMed:12105218, PubMed:21854986, PubMed:32972995). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:12105218, PubMed:28165510, PubMed:9121453). {ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:10556041, ECO:0000269|PubMed:11682488, ECO:0000269|PubMed:12105218, ECO:0000269|PubMed:17517919, ECO:0000269|PubMed:21854986, ECO:0000269|PubMed:26424569, ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:7759950, ECO:0000269|PubMed:8181059, ECO:0000269|PubMed:8798579, ECO:0000269|PubMed:8969169, ECO:0000269|PubMed:9121453}.; FUNCTION: [Isoform 3]: Potent inhibitor of type I IFN receptor activity. {ECO:0000269|PubMed:7759950}. |
| P49137 | MAPKAPK2 | Y225 | ochoa | MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) | Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}. |
| P49407 | ARRB1 | Y47 | ochoa | Beta-arrestin-1 (Arrestin beta-1) (Non-visual arrestin-2) | Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as a signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as a signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) (By similarity). Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940). {ECO:0000250, ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15611106, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:18337459, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:23886940}. |
| P49795 | RGS19 | Y146 | ochoa | Regulator of G-protein signaling 19 (RGS19) (G-alpha-interacting protein) (GAIP) | Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G-alpha subfamily 1 members, with the order G(i)a3 > G(i)a1 > G(o)a >> G(z)a/G(i)a2. Activity on G(z)-alpha is inhibited by phosphorylation and palmitoylation of the G-protein. |
| P50395 | GDI2 | Y203 | ochoa | Rab GDP dissociation inhibitor beta (Rab GDI beta) (Guanosine diphosphate dissociation inhibitor 2) (GDI-2) | GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking (PubMed:25860027). Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A (PubMed:25860027). {ECO:0000269|PubMed:25860027}. |
| P50452 | SERPINB8 | Y166 | ochoa | Serpin B8 (Cytoplasmic antiproteinase 2) (CAP-2) (CAP2) (Peptidase inhibitor 8) (PI-8) | Has an important role in epithelial desmosome-mediated cell-cell adhesion. {ECO:0000269|PubMed:27476651}. |
| P50453 | SERPINB9 | Y166 | ochoa | Serpin B9 (Cytoplasmic antiproteinase 3) (CAP-3) (CAP3) (Peptidase inhibitor 9) (PI-9) | Granzyme B inhibitor. |
| P50479 | PDLIM4 | Y191 | ochoa | PDZ and LIM domain protein 4 (LIM protein RIL) (Reversion-induced LIM protein) | [Isoform 1]: Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity). {ECO:0000250|UniProtKB:P36202, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:21636573}.; FUNCTION: [Isoform 2]: Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration. {ECO:0000269|PubMed:21636573}. |
| P50990 | CCT8 | Y30 | ochoa | T-complex protein 1 subunit theta (TCP-1-theta) (EC 3.6.1.-) (CCT-theta) (Chaperonin containing T-complex polypeptide 1 subunit 8) (Renal carcinoma antigen NY-REN-15) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P51451 | BLK | Y187 | ochoa | Tyrosine-protein kinase Blk (EC 2.7.10.2) (B lymphocyte kinase) (p55-Blk) | Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). {ECO:0000250|UniProtKB:P16277, ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:8756631}. |
| P51798 | CLCN7 | Y94 | ochoa | H(+)/Cl(-) exchange transporter 7 (Chloride channel 7 alpha subunit) (Chloride channel protein 7) (ClC-7) | Slowly voltage-gated channel mediating the exchange of chloride ions against protons (PubMed:18449189, PubMed:21527911). Functions as antiporter and contributes to the acidification of the lysosome lumen and may be involved in maintaining lysosomal pH (PubMed:18449189, PubMed:21527911, PubMed:31155284). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (By similarity). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity). {ECO:0000250|UniProtKB:P35523, ECO:0000269|PubMed:18449189, ECO:0000269|PubMed:21527911, ECO:0000269|PubMed:31155284}. |
| P51812 | RPS6KA3 | Y580 | ochoa|psp | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
| P52306 | RAP1GDS1 | Y118 | ochoa | Rap1 GTPase-GDP dissociation stimulator 1 (Exchange factor smgGDS) (SMG GDS protein) (SMG P21 stimulatory GDP/GTP exchange protein) | Acts as a GEF (guanine nucleotide exchange factor) for the Rho family of small GTP-binding proteins (G proteins) that stimulates the dissociation of GDP to enable subsequent binding of GTP (PubMed:11948427, PubMed:1549351, PubMed:20709748, PubMed:28630045, PubMed:30190425). Additionally, appears to chaperone the processing and/or trafficking of small GTPases containing a C-terminal polybasic region independently of GEF activity (PubMed:20709748, PubMed:21242305). Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1 and KRAS (PubMed:11948427, PubMed:1549351, PubMed:20709748, PubMed:24415755). Regulates mitochondrial dynamics by controlling RHOT function to promote mitochondrial fission during high calcium conditions (PubMed:27716788). Able to promote the Ca(2+) release from the endoplasmic reticulum via both inositol trisphosphate (Ins3P) and ryanodine sensitive receptors leading to a enhanced mitochondrial Ca(2+) uptake (PubMed:24349085). {ECO:0000269|PubMed:11948427, ECO:0000269|PubMed:1549351, ECO:0000269|PubMed:20709748, ECO:0000269|PubMed:21242305, ECO:0000269|PubMed:24349085, ECO:0000269|PubMed:24415755, ECO:0000269|PubMed:27716788, ECO:0000269|PubMed:28630045, ECO:0000269|PubMed:30190425, ECO:0000305|PubMed:30190425}.; FUNCTION: [Isoform 1]: Acts as a GEF (guanine nucleotide exchange factor) for unprenylated RHOA (PubMed:24415755, PubMed:28630045, PubMed:30190425). Chaperones the entry and passage of small GTPases through the prenylation pathway (PubMed:20709748). Recognizes the last amino acid in the GTPase C-terminal CAAX motif with a preference for 'Leu' over 'Met', indicating involvement in the geranylgeranylation pathway (PubMed:24415755). {ECO:0000269|PubMed:20709748, ECO:0000269|PubMed:24415755, ECO:0000269|PubMed:28630045, ECO:0000269|PubMed:30190425}.; FUNCTION: [Isoform 2]: Acts as a GEF (guanine nucleotide exchange factor) for prenylated RHOA (PubMed:21242305, PubMed:28630045, PubMed:30190425). Acts as a GEF for RHOC (PubMed:21242305). Chaperones the downstream trafficking and/or processing of small newly prenylated GTPases (PubMed:20709748). Escorts RAC1 to the nucleus (PubMed:12551911). {ECO:0000269|PubMed:12551911, ECO:0000269|PubMed:20709748, ECO:0000269|PubMed:21242305, ECO:0000269|PubMed:28630045, ECO:0000269|PubMed:30190425}. |
| P52333 | JAK3 | Y785 | psp | Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK) | Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:20440074, ECO:0000269|PubMed:7662955, ECO:0000269|PubMed:8022485}. |
| P52735 | VAV2 | Y159 | ochoa|psp | Guanine nucleotide exchange factor VAV2 (VAV-2) | Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). {ECO:0000250}. |
| P52895 | AKR1C2 | Y24 | ochoa | Aldo-keto reductase family 1 member C2 (EC 1.-.-.-) (EC 1.1.1.112) (EC 1.1.1.209) (EC 1.1.1.53) (EC 1.1.1.62) (EC 1.3.1.20) (3-alpha-HSD3) (Chlordecone reductase homolog HAKRD) (Dihydrodiol dehydrogenase 2) (DD-2) (DD2) (Dihydrodiol dehydrogenase/bile acid-binding protein) (DD/BABP) (Type III 3-alpha-hydroxysteroid dehydrogenase) (EC 1.1.1.357) | Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (PubMed:14672942). Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:10998348). Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:15929998, PubMed:17034817, PubMed:17442338, PubMed:8573067). Also specifically able to produce 17beta-hydroxy-5alpha-androstan-3-one/5alphaDHT (PubMed:10998348). May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for bile acids (PubMed:8486699). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699, ECO:0000269|PubMed:8573067}. |
| P53004 | BLVRA | Y228 | psp | Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) | Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}. |
| P55317 | FOXA1 | Y429 | psp | 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}. |
| P58335 | ANTXR2 | Y463 | psp | Anthrax toxin receptor 2 (Capillary morphogenesis gene 2 protein) (CMG-2) | Necessary for cellular interactions with laminin and the extracellular matrix. {ECO:0000269|PubMed:11683410, ECO:0000269|PubMed:12973667}.; FUNCTION: (Microbial infection) Receptor for the protective antigen (PA) of B.anthracis (PubMed:12700348, PubMed:15243628, PubMed:15326297). Binding of PA leads to heptamerization of the receptor-PA complex (PubMed:12700348, PubMed:15243628, PubMed:15326297). Upon binding of the PA of B.anthracis, the complex moves to glycosphingolipid-rich lipid rafts, where it is internalized via a clathrin-dependent pathway (PubMed:12551953, PubMed:15337774). In the endosomal membrane, at pH under 7, the complex then rearranges and forms a pore allowing the other components of anthrax toxin to escape to the cytoplasm (PubMed:12551953, PubMed:15337774). {ECO:0000269|PubMed:12551953, ECO:0000269|PubMed:12700348, ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:15337774}. |
| P60709 | ACTB | Y198 | ochoa | Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] | Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}. |
| P60842 | EIF4A1 | Y48 | ochoa | Eukaryotic initiation factor 4A-I (eIF-4A-I) (eIF4A-I) (EC 3.6.4.13) (ATP-dependent RNA helicase eIF4A-1) | ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome (PubMed:20156963). In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. As a result, promotes cell proliferation and growth (PubMed:20156963). {ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291, ECO:0000269|PubMed:20156963}. |
| P61160 | ACTR2 | Y202 | psp | Actin-related protein 2 (Actin-like protein 2) | ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9000076). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9000076). Seems to contact the pointed end of the daughter actin filament (PubMed:9000076). In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation (PubMed:29058690). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:17220302, PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:17220302, ECO:0000269|PubMed:29058690, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9000076}. |
| P61758 | VBP1 | Y112 | ochoa | Prefoldin subunit 3 (HIBBJ46) (von Hippel-Lindau-binding protein 1) (VBP-1) (VHL-binding protein 1) | Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. {ECO:0000269|PubMed:9630229}. |
| P61978 | HNRNPK | Y138 | ochoa | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P61981 | YWHAG | Y49 | ochoa | 14-3-3 protein gamma (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein gamma, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927). {ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:22532927, ECO:0000269|PubMed:29121962, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:36732624}. |
| P61981 | YWHAG | Y216 | ochoa | 14-3-3 protein gamma (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein gamma, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927). {ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:22532927, ECO:0000269|PubMed:29121962, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:36732624}. |
| P62258 | YWHAE | Y49 | ochoa | 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}. |
| P62258 | YWHAE | Y214 | ochoa|psp | 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}. |
| P62736 | ACTA2 | Y200 | ochoa | Actin, aortic smooth muscle (EC 3.6.4.-) (Alpha-actin-2) (Cell growth-inhibiting gene 46 protein) [Cleaved into: Actin, aortic smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P63104 | YWHAZ | Y48 | ochoa | 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}. |
| P63104 | YWHAZ | Y211 | ochoa | 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}. |
| P63261 | ACTG1 | Y198 | ochoa|psp | Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}. |
| P63267 | ACTG2 | Y199 | ochoa | Actin, gamma-enteric smooth muscle (EC 3.6.4.-) (Alpha-actin-3) (Gamma-2-actin) (Smooth muscle gamma-actin) [Cleaved into: Actin, gamma-enteric smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68032 | ACTC1 | Y200 | ochoa | Actin, alpha cardiac muscle 1 (EC 3.6.4.-) (Alpha-cardiac actin) [Cleaved into: Actin, alpha cardiac muscle 1, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68133 | ACTA1 | Y200 | ochoa | Actin, alpha skeletal muscle (EC 3.6.4.-) (Alpha-actin-1) [Cleaved into: Actin, alpha skeletal muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68363 | TUBA1B | Y224 | ochoa | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P68366 | TUBA4A | Y224 | ochoa | Tubulin alpha-4A chain (EC 3.6.5.-) (Alpha-tubulin 1) (Testis-specific alpha-tubulin) (Tubulin H2-alpha) (Tubulin alpha-1 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P68371 | TUBB4B | Y222 | ochoa | Tubulin beta-4B chain (Tubulin beta-2 chain) (Tubulin beta-2C chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P78337 | PITX1 | Y160 | psp | Pituitary homeobox 1 (Hindlimb-expressed homeobox protein backfoot) (Homeobox protein PITX1) (Paired-like homeodomain transcription factor 1) | Sequence-specific transcription factor that binds gene promoters and activates their transcription. May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb. {ECO:0000250|UniProtKB:P56673}. |
| P82094 | TMF1 | Y353 | ochoa | TATA element modulatory factor (TMF) (Androgen receptor coactivator 160 kDa protein) (Androgen receptor-associated protein of 160 kDa) | Potential coactivator of the androgen receptor. Mediates STAT3 degradation. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. This protein binds the HIV-1 TATA element and inhibits transcriptional activation by the TATA-binding protein (TBP). {ECO:0000269|PubMed:10428808, ECO:0000269|PubMed:1409643, ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:17698061}. |
| Q00341 | HDLBP | Y582 | ochoa | Vigilin (High density lipoprotein-binding protein) (HDL-binding protein) | Appears to play a role in cell sterol metabolism. It may function to protect cells from over-accumulation of cholesterol. |
| Q00536 | CDK16 | Y176 | ochoa | Cyclin-dependent kinase 16 (EC 2.7.11.22) (Cell division protein kinase 16) (PCTAIRE-motif protein kinase 1) (Serine/threonine-protein kinase PCTAIRE-1) | Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}. |
| Q00537 | CDK17 | Y203 | ochoa | Cyclin-dependent kinase 17 (EC 2.7.11.22) (Cell division protein kinase 17) (PCTAIRE-motif protein kinase 2) (Serine/threonine-protein kinase PCTAIRE-2) | May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}. |
| Q00610 | CLTC | Y899 | ochoa | Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| Q01082 | SPTBN1 | Y493 | ochoa | Spectrin beta chain, non-erythrocytic 1 (Beta-II spectrin) (Fodrin beta chain) (Spectrin, non-erythroid beta chain 1) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function. {ECO:0000269|PubMed:34211179}. |
| Q01082 | SPTBN1 | Y2039 | ochoa | Spectrin beta chain, non-erythrocytic 1 (Beta-II spectrin) (Fodrin beta chain) (Spectrin, non-erythroid beta chain 1) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function. {ECO:0000269|PubMed:34211179}. |
| Q01201 | RELB | Y293 | ochoa | Transcription factor RelB (I-Rel) | NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function (PubMed:26385063). {ECO:0000269|PubMed:1732739, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:26385063, ECO:0000269|PubMed:7925301, ECO:0000269|PubMed:8441398}. |
| Q01973 | ROR1 | Y786 | ochoa | Inactive tyrosine-protein kinase transmembrane receptor ROR1 (Neurotrophic tyrosine kinase, receptor-related 1) | Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350). Via IGFBP5 ligand, forms a complex with ERBB2 to enhance CREB oncogenic signaling (PubMed:36949068). {ECO:0000269|PubMed:25029443, ECO:0000269|PubMed:27162350, ECO:0000269|PubMed:36949068}. |
| Q04828 | AKR1C1 | Y24 | ochoa | Aldo-keto reductase family 1 member C1 (EC 1.1.1.-) (EC 1.1.1.112) (EC 1.1.1.209) (EC 1.1.1.210) (EC 1.1.1.357) (EC 1.1.1.51) (EC 1.1.1.53) (EC 1.1.1.62) (EC 1.3.1.20) (20-alpha-hydroxysteroid dehydrogenase) (20-alpha-HSD) (EC 1.1.1.149) (Chlordecone reductase homolog HAKRC) (Dihydrodiol dehydrogenase 1) (DD1) (High-affinity hepatic bile acid-binding protein) (HBAB) | Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (PubMed:14672942). Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:10998348). May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for bile acids (PubMed:8486699). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699}. |
| Q04837 | SSBP1 | Y99 | ochoa | Single-stranded DNA-binding protein, mitochondrial (Mt-SSB) (MtSSB) (PWP1-interacting protein 17) | Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA) (PubMed:21953457, PubMed:23290262, PubMed:31550240). In vitro, required to maintain the copy number of mitochondrial DNA (mtDNA) and plays a crucial role during mtDNA replication by stimulating the activity of the replisome components POLG and TWNK at the replication fork (PubMed:12975372, PubMed:15167897, PubMed:21953457, PubMed:26446790, PubMed:31550240). Promotes the activity of the gamma complex polymerase POLG, largely by organizing the template DNA and eliminating secondary structures to favor ss-DNA conformations that facilitate POLG activity (PubMed:21953457, PubMed:26446790, PubMed:31550240). In addition it is able to promote the 5'-3' unwinding activity of the mtDNA helicase TWNK (PubMed:12975372). May also function in mtDNA repair (PubMed:23290262). {ECO:0000269|PubMed:12975372, ECO:0000269|PubMed:15167897, ECO:0000269|PubMed:21953457, ECO:0000269|PubMed:23290262, ECO:0000269|PubMed:26446790, ECO:0000269|PubMed:31550240}. |
| Q04917 | YWHAH | Y49 | ochoa | 14-3-3 protein eta (Protein AS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| Q05513 | PRKCZ | Y428 | psp | Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta) | Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro (PubMed:17313651). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9447975}.; FUNCTION: [Isoform 2]: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance. {ECO:0000250|UniProtKB:Q02956}. |
| Q05655 | PRKCD | Y187 | psp | Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}. |
| Q05655 | PRKCD | Y525 | psp | Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}. |
| Q06210 | GFPT1 | Y553 | ochoa | Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1 (EC 2.6.1.16) (D-fructose-6-phosphate amidotransferase 1) (Glutamine:fructose-6-phosphate amidotransferase 1) (GFAT 1) (GFAT1) (Hexosephosphate aminotransferase 1) | Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (PubMed:26887390). {ECO:0000250|UniProtKB:P47856, ECO:0000269|PubMed:26887390}. |
| Q07157 | TJP1 | Y1059 | ochoa | Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) | TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}. |
| Q08999 | RBL2 | Y408 | ochoa | Retinoblastoma-like protein 2 (130 kDa retinoblastoma-associated protein) (p130) (Retinoblastoma-related protein 2) (RBR-2) (pRb2) | Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor. |
| Q12774 | ARHGEF5 | Y1100 | ochoa | Rho guanine nucleotide exchange factor 5 (Ephexin-3) (Guanine nucleotide regulatory protein TIM) (Oncogene TIM) (Transforming immortalized mammary oncogene) (p60 TIM) | Guanine nucleotide exchange factor which activates Rho GTPases (PubMed:15601624). Strongly activates RHOA (PubMed:15601624). Also strongly activates RHOB, weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ or RAC1 (By similarity). Involved in regulation of cell shape and actin cytoskeletal organization (PubMed:15601624). Plays a role in actin organization by generating a loss of actin stress fibers and the formation of membrane ruffles and filopodia (PubMed:14662653). Required for SRC-induced podosome formation (By similarity). Involved in positive regulation of immature dendritic cell migration (By similarity). {ECO:0000250|UniProtKB:E9Q7D5, ECO:0000269|PubMed:14662653, ECO:0000269|PubMed:15601624}. |
| Q12789 | GTF3C1 | Y1652 | ochoa | General transcription factor 3C polypeptide 1 (TF3C-alpha) (TFIIIC box B-binding subunit) (Transcription factor IIIC 220 kDa subunit) (TFIIIC 220 kDa subunit) (TFIIIC220) (Transcription factor IIIC subunit alpha) | Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element. |
| Q12846 | STX4 | Y251 | ochoa | Syntaxin-4 (Renal carcinoma antigen NY-REN-31) | Plasma membrane t-SNARE that mediates docking of transport vesicles (By similarity). Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane (By similarity). In neurons, recruited at neurite tips to membrane domains rich in the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) which promotes neurite tip surface expression of the dopamine transporter SLC6A3/DAT by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity). Together with STXB3 and VAMP2, may also play a role in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes and in docking of synaptic vesicles at presynaptic active zones (By similarity). Required for normal hearing (PubMed:36355422). {ECO:0000250|UniProtKB:P70452, ECO:0000250|UniProtKB:Q08850, ECO:0000269|PubMed:36355422}. |
| Q12866 | MERTK | Y749 | psp | Tyrosine-protein kinase Mer (EC 2.7.10.1) (Proto-oncogene c-Mer) (Receptor tyrosine kinase MerTK) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment (PubMed:32640697). Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:32640697}. |
| Q12879 | GRIN2A | Y1325 | psp | Glutamate receptor ionotropic, NMDA 2A (GluN2A) (Glutamate [NMDA] receptor subunit epsilon-1) (N-methyl D-aspartate receptor subtype 2A) (NMDAR2A) (NR2A) (hNR2A) | Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:20890276, PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:28242877, PubMed:36117210, PubMed:38538865, PubMed:8768735). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:27288002, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28182669, PubMed:29644724, PubMed:38307912, PubMed:8768735). NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761). Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte (By similarity). {ECO:0000250|UniProtKB:P35436, ECO:0000250|UniProtKB:P35438, ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23933818, ECO:0000269|PubMed:23933819, ECO:0000269|PubMed:23933820, ECO:0000269|PubMed:24504326, ECO:0000269|PubMed:26875626, ECO:0000269|PubMed:26919761, ECO:0000269|PubMed:27288002, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28105280, ECO:0000269|PubMed:28126851, ECO:0000269|PubMed:28182669, ECO:0000269|PubMed:28242877, ECO:0000269|PubMed:29644724, ECO:0000269|PubMed:36117210, ECO:0000269|PubMed:38307912, ECO:0000269|PubMed:38538865, ECO:0000269|PubMed:8768735}. |
| Q12888 | TP53BP1 | Y522 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q13114 | TRAF3 | Y116 | psp | TNF receptor-associated factor 3 (EC 2.3.2.27) (CD40 receptor-associated factor 1) (CRAF1) (CD40-binding protein) (CD40BP) (LMP1-associated protein 1) (LAP1) (RING-type E3 ubiquitin transferase TRAF3) | Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed:33148796, PubMed:33608556). In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome (PubMed:25847972, PubMed:27980081). Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance (PubMed:27438768). Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20185819, ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:32562145, ECO:0000269|PubMed:33148796, ECO:0000269|PubMed:33608556, ECO:0000269|PubMed:34011520}. |
| Q13507 | TRPC3 | Y122 | psp | Short transient receptor potential channel 3 (TrpC3) (Transient receptor protein 3) (TRP-3) (hTrp-3) (hTrp3) | Forms a receptor-activated non-selective calcium permeant cation channel (PubMed:29726814, PubMed:30139744, PubMed:35051376, PubMed:9417057, PubMed:9930701, PubMed:10611319). {ECO:0000269|PubMed:10611319, ECO:0000269|PubMed:29726814, ECO:0000269|PubMed:30139744, ECO:0000269|PubMed:35051376, ECO:0000269|PubMed:9417057, ECO:0000269|PubMed:9930701}.; FUNCTION: [Isoform 2]: Forms a receptor-activated non-selective calcium permeant cation channel. May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. {ECO:0000269|PubMed:8646775}. |
| Q13507 | TRPC3 | Y299 | psp | Short transient receptor potential channel 3 (TrpC3) (Transient receptor protein 3) (TRP-3) (hTrp-3) (hTrp3) | Forms a receptor-activated non-selective calcium permeant cation channel (PubMed:29726814, PubMed:30139744, PubMed:35051376, PubMed:9417057, PubMed:9930701, PubMed:10611319). {ECO:0000269|PubMed:10611319, ECO:0000269|PubMed:29726814, ECO:0000269|PubMed:30139744, ECO:0000269|PubMed:35051376, ECO:0000269|PubMed:9417057, ECO:0000269|PubMed:9930701}.; FUNCTION: [Isoform 2]: Forms a receptor-activated non-selective calcium permeant cation channel. May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. {ECO:0000269|PubMed:8646775}. |
| Q13523 | PRP4K | Y140 | ochoa | Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) | Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}. |
| Q13576 | IQGAP2 | Y1071 | ochoa | Ras GTPase-activating-like protein IQGAP2 | Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin. |
| Q13885 | TUBB2A | Y222 | ochoa | Tubulin beta-2A chain (Tubulin beta class IIa) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q14126 | DSG2 | Y979 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14126 | DSG2 | Y1013 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14192 | FHL2 | Y236 | psp | Four and a half LIM domains protein 2 (FHL-2) (LIM domain protein DRAL) (Skeletal muscle LIM-protein 3) (SLIM-3) | May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation. Negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes (PubMed:28717008). {ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:16652157, ECO:0000269|PubMed:18853468, ECO:0000269|PubMed:28717008}. |
| Q14240 | EIF4A2 | Y49 | ochoa | Eukaryotic initiation factor 4A-II (eIF-4A-II) (eIF4A-II) (EC 3.6.4.13) (ATP-dependent RNA helicase eIF4A-2) | ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. |
| Q14289 | PTK2B | Y834 | ochoa | Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) | Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. |
| Q14289 | PTK2B | Y906 | psp | Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) | Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. |
| Q14517 | FAT1 | Y4242 | ochoa | Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form] | [Protocadherin Fat 1]: Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. {ECO:0000250}. |
| Q15052 | ARHGEF6 | Y719 | ochoa | Rho guanine nucleotide exchange factor 6 (Alpha-Pix) (COOL-2) (PAK-interacting exchange factor alpha) (Rac/Cdc42 guanine nucleotide exchange factor 6) | Acts as a RAC1 guanine nucleotide exchange factor (GEF). |
| Q15118 | PDK1 | Y244 | psp | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (EC 2.7.11.2) (Pyruvate dehydrogenase kinase isoform 1) (PDH kinase 1) | Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2 (PubMed:7499431, PubMed:18541534, PubMed:22195962, PubMed:26942675, PubMed:17683942). This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate (PubMed:18541534, PubMed:22195962, PubMed:26942675). Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia (PubMed:18541534, PubMed:22195962, PubMed:26942675). {ECO:0000269|PubMed:17683942, ECO:0000269|PubMed:18541534, ECO:0000269|PubMed:22195962, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:7499431}. |
| Q15303 | ERBB4 | Y1188 | psp | Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)] | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}. |
| Q15303 | ERBB4 | Y1221 | psp | Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)] | Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}. |
| Q15418 | RPS6KA1 | Y576 | ochoa | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q15785 | TOMM34 | Y230 | ochoa | Mitochondrial import receptor subunit TOM34 (hTom34) (Translocase of outer membrane 34 kDa subunit) | Plays a role in the import of cytosolically synthesized preproteins into mitochondria. Binds the mature portion of precursor proteins. Interacts with cellular components, and possesses weak ATPase activity. May be a chaperone-like protein that helps to keep newly synthesized precursors in an unfolded import compatible state. {ECO:0000269|PubMed:10101285, ECO:0000269|PubMed:11913975, ECO:0000269|PubMed:9324309}. |
| Q15811 | ITSN1 | Y1208 | ochoa | Intersectin-1 (SH3 domain-containing protein 1A) (SH3P17) | Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery (PubMed:11584276, PubMed:29887380). Acts as a guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex (PubMed:11584276). Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits (PubMed:29887380). Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (By similarity). Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2 (PubMed:22648170). Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways. In chromaffin cells, required for normal exocytosis of catecholamines. Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones (By similarity). Inhibits ARHGAP31 activity toward RAC1 (PubMed:11744688). {ECO:0000250|UniProtKB:Q9WVE9, ECO:0000250|UniProtKB:Q9Z0R4, ECO:0000269|PubMed:11584276, ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:29887380}.; FUNCTION: [Isoform 1]: Plays a role in synaptic vesicle endocytosis in brain neurons. {ECO:0000250|UniProtKB:Q9Z0R4}. |
| Q16181 | SEPTIN7 | Y319 | ochoa|psp | Septin-7 (CDC10 protein homolog) | Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Required for normal progress through mitosis. Involved in cytokinesis. Required for normal association of CENPE with the kinetochore. Plays a role in ciliogenesis and collective cell movements. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). {ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18460473, ECO:0000305|PubMed:25588830}. |
| Q16595 | FXN | Y118 | psp | Frataxin, mitochondrial (EC 1.16.3.1) (Friedreich ataxia protein) (Fxn) [Cleaved into: Frataxin intermediate form (i-FXN); Frataxin(56-210) (m56-FXN); Frataxin(78-210) (d-FXN) (m78-FXN); Frataxin mature form (Frataxin(81-210)) (m81-FXN); Extramitochondrial frataxin] | [Frataxin mature form]: Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:12785837, PubMed:24971490). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:24971490). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (PubMed:29576242). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity (PubMed:15641778). May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems (PubMed:11823441, PubMed:12755598). May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation (PubMed:15247478). May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (PubMed:15123683, PubMed:16239244). {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000269|PubMed:11823441, ECO:0000269|PubMed:12755598, ECO:0000269|PubMed:12785837, ECO:0000269|PubMed:15123683, ECO:0000269|PubMed:15247478, ECO:0000269|PubMed:15641778, ECO:0000269|PubMed:16239244, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:29576242}.; FUNCTION: [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1 (PubMed:20053667). May be involved in the cytoplasmic iron-sulfur protein biogenesis (PubMed:16091420). May contribute to oxidative stress resistance and overall cell survival (PubMed:16608849). {ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}. |
| Q16644 | MAPKAPK3 | Y204 | ochoa | MAP kinase-activated protein kinase 3 (MAPK-activated protein kinase 3) (MAPKAP kinase 3) (MAPKAP-K3) (MAPKAPK-3) (MK-3) (EC 2.7.11.1) (Chromosome 3p kinase) (3pK) | Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}. |
| Q2NKX8 | ERCC6L | Y867 | ochoa | DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) | DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}. |
| Q49AG3 | ZBED5 | Y476 | ochoa | Zinc finger BED domain-containing protein 5 (Transposon-derived Buster1 transposase-like protein) | None |
| Q53EZ4 | CEP55 | Y284 | ochoa | Centrosomal protein of 55 kDa (Cep55) (Up-regulated in colon cancer 6) | Plays a role in mitotic exit and cytokinesis (PubMed:16198290, PubMed:17853893). Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis (PubMed:17853893). Not required for microtubule nucleation (PubMed:16198290). Plays a role in the development of the brain and kidney (PubMed:28264986). {ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:28264986}. |
| Q58FF6 | HSP90AB4P | Y32 | ochoa | Putative heat shock protein HSP 90-beta 4 | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q58FF7 | HSP90AB3P | Y56 | ochoa | Putative heat shock protein HSP 90-beta-3 (Heat shock protein 90-beta c) (Heat shock protein 90Bc) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q58FF8 | HSP90AB2P | Y56 | ochoa | Putative heat shock protein HSP 90-beta 2 (Heat shock protein 90-beta b) (Heat shock protein 90Bb) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q5JTD0 | TJAP1 | Y352 | ochoa | Tight junction-associated protein 1 (Protein incorporated later into tight junctions) (Tight junction protein 4) | Plays a role in regulating the structure of the Golgi apparatus. {ECO:0000250|UniProtKB:Q9DCD5}. |
| Q5K651 | SAMD9 | Y164 | ochoa | Sterile alpha motif domain-containing protein 9 (SAM domain-containing protein 9) | Double-stranded nucleic acid binding that acts as an antiviral factor by playing an essential role in the formation of cytoplasmic antiviral granules (PubMed:25428864, PubMed:28157624). May play a role in the inflammatory response to tissue injury and the control of extra-osseous calcification, acting as a downstream target of TNF-alpha signaling. Involved in the regulation of EGR1, in coordination with RGL2. May be involved in endosome fusion. {ECO:0000269|PubMed:16960814, ECO:0000269|PubMed:18094730, ECO:0000269|PubMed:21160498, ECO:0000269|PubMed:24029230, ECO:0000269|PubMed:25428864, ECO:0000269|PubMed:28157624}. |
| Q5MJ10 | SPANXN2 | Y55 | ochoa | Sperm protein associated with the nucleus on the X chromosome N2 (Nuclear-associated protein SPAN-Xn2) (SPANX-N2) (SPANX family member N2) | None |
| Q5T6F2 | UBAP2 | Y840 | ochoa | Ubiquitin-associated protein 2 (UBAP-2) (RNA polymerase II degradation factor UBAP2) | Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). May promote the degradation of ANXA2 (PubMed:27121050). {ECO:0000269|PubMed:27121050, ECO:0000269|PubMed:35633597}. |
| Q5TCX8 | MAP3K21 | Y669 | ochoa | Mitogen-activated protein kinase kinase kinase 21 (EC 2.7.11.25) (Mitogen-activated protein kinase kinase kinase MLK4) (Mixed lineage kinase 4) | Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1 pathways. {ECO:0000269|PubMed:21602844}. |
| Q5THJ4 | VPS13D | Y1705 | ochoa | Intermembrane lipid transfer protein VPS13D (Vacuolar protein sorting-associated protein 13D) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Functions in promoting mitochondrial clearance by mitochondrial autophagy (mitophagy), also possibly by positively regulating mitochondrial fission (PubMed:29307555, PubMed:29604224). Mitophagy plays an important role in regulating cell health and mitochondrial size and homeostasis. {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:29307555, ECO:0000269|PubMed:29604224}. |
| Q5VT52 | RPRD2 | Y962 | ochoa | Regulation of nuclear pre-mRNA domain-containing protein 2 | None |
| Q63HR2 | TNS2 | Y626 | ochoa | Tensin-2 (EC 3.1.3.48) (C1 domain-containing phosphatase and tensin homolog) (C1-TEN) (Tensin-like C1 domain-containing phosphatase) | Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin (PubMed:15817639, PubMed:23401856). Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain (PubMed:30092354). In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy (PubMed:23401856, PubMed:30092354). Negatively regulates PI3K-AKT pathway activation (PubMed:15817639, PubMed:23401856, PubMed:30092354). Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex (PubMed:28955049). Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria (PubMed:28955049). Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix (PubMed:20069572). {ECO:0000250|UniProtKB:Q8CGB6, ECO:0000269|PubMed:15817639, ECO:0000269|PubMed:20069572, ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:28955049, ECO:0000269|PubMed:30092354}. |
| Q68CZ2 | TNS3 | Y780 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q6NUN9 | ZNF746 | Y137 | psp | Zinc finger protein 746 (Parkin-interacting substrate) (PARIS) | Transcription repressor that specifically binds to the 5'-TATTTT[T/G]-3' consensus sequence on promoters and repress transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death. {ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:31856708}. |
| Q6P1R3 | MSANTD2 | Y427 | ochoa | Myb/SANT-like DNA-binding domain-containing protein 2 | None |
| Q6PEY2 | TUBA3E | Y224 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q6PIY7 | TENT2 | Y58 | ochoa | Poly(A) RNA polymerase GLD2 (hGLD-2) (EC 2.7.7.19) (PAP-associated domain-containing protein 4) (Terminal nucleotidyltransferase 2) (Terminal uridylyltransferase 2) (TUTase 2) | Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail (PubMed:15070731, PubMed:31792053). In contrast to the canonical nuclear poly(A) RNA polymerase, it only adds poly(A) to selected cytoplasmic mRNAs (PubMed:15070731). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Adds a single nucleotide to the 3' end of specific miRNAs, monoadenylation stabilizes and prolongs the activity of some but not all miRNAs (PubMed:23200856, PubMed:31792053). {ECO:0000269|PubMed:15070731, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:23200856, ECO:0000269|PubMed:31792053}. |
| Q6UUV7 | CRTC3 | Y58 | ochoa | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UX68 | XKR5 | Y487 | psp | XK-related protein 5 | None |
| Q6XZF7 | DNMBP | Y429 | ochoa | Dynamin-binding protein (Scaffold protein Tuba) | Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells (PubMed:17015620, PubMed:19767742). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (PubMed:20479467). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (By similarity). {ECO:0000250|UniProtKB:E2RP94, ECO:0000250|UniProtKB:Q6TXD4, ECO:0000269|PubMed:17015620, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20479467}. |
| Q6ZV73 | FGD6 | Y748 | ochoa | FYVE, RhoGEF and PH domain-containing protein 6 (Zinc finger FYVE domain-containing protein 24) | May activate CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. May play a role in regulating the actin cytoskeleton and cell shape (By similarity). {ECO:0000250}. |
| Q71U36 | TUBA1A | Y224 | ochoa | Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 3) (Tubulin B-alpha-1) (Tubulin alpha-3 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q7L591 | DOK3 | Y381 | ochoa | Docking protein 3 (Downstream of tyrosine kinase 3) | DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK3 is a negative regulator of JNK signaling in B-cells through interaction with INPP5D/SHIP1. May modulate ABL1 function (By similarity). {ECO:0000250}. |
| Q7Z2W4 | ZC3HAV1 | Y410 | ochoa | Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13) (ARTD13) (Inactive Poly [ADP-ribose] polymerase 13) (PARP13) (Zinc finger CCCH domain-containing protein 2) (Zinc finger antiviral protein) (ZAP) | Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}. |
| Q7Z6Z7 | HUWE1 | Y3214 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q86U86 | PBRM1 | Y366 | ochoa | Protein polybromo-1 (hPB1) (BRG1-associated factor 180) (BAF180) (Polybromo-1D) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation. {ECO:0000269|PubMed:21248752, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q86V48 | LUZP1 | Y414 | ochoa | Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) | F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}. |
| Q8IUQ4 | SIAH1 | Y100 | psp | E3 ubiquitin-protein ligase SIAH1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase SIAH1) (Seven in absentia homolog 1) (Siah-1) (Siah-1a) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:28546513, PubMed:32430360, PubMed:33591310, PubMed:9334332, PubMed:9858595). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443). Confers constitutive instability to HIPK2 through proteasomal degradation (PubMed:18536714, PubMed:33591310). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Has some overlapping function with SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (PubMed:28546513, PubMed:32430360). {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}. |
| Q8IWB9 | TEX2 | Y299 | ochoa | Testis-expressed protein 2 (Transmembrane protein 96) | During endoplasmic reticulum (ER) stress or when cellular ceramide levels increase, may induce contacts between the ER and medial-Golgi complex to facilitate non-vesicular transport of ceramides from the ER to the Golgi complex where they are converted to complex sphingolipids, preventing toxic ceramide accumulation. {ECO:0000269|PubMed:28011845}. |
| Q8IX03 | WWC1 | Y128 | ochoa | Protein KIBRA (HBeAg-binding protein 3) (Kidney and brain protein) (KIBRA) (WW domain-containing protein 1) | Regulator of the Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway (PubMed:24682284). Enhances phosphorylation of LATS1 and YAP1 and negatively regulates cell proliferation and organ growth due to a suppression of the transcriptional activity of YAP1, the major effector of the Hippo pathway (PubMed:24682284). Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and function in the regulation of Hippo signaling pathway (PubMed:20159598). Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation (PubMed:16684779). Regulates collagen-stimulated activation of the ERK/MAPK cascade (PubMed:18190796). Modulates directional migration of podocytes (PubMed:18596123). Plays a role in cognition and memory performance (PubMed:18672031). Plays an important role in regulating AMPA-selective glutamate receptors (AMPARs) trafficking underlying synaptic plasticity and learning (By similarity). {ECO:0000250|UniProtKB:Q5SXA9, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:24682284}. |
| Q8IX12 | CCAR1 | Y192 | psp | Cell division cycle and apoptosis regulator protein 1 (Cell cycle and apoptosis regulatory protein 1) (CARP-1) (Death inducer with SAP domain) | Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation (By similarity). May be involved in apoptosis signaling in the presence of the reinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation (PubMed:12816952). In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells (PubMed:23887938). {ECO:0000250|UniProtKB:Q8CH18, ECO:0000269|PubMed:12816952, ECO:0000269|PubMed:23887938, ECO:0000269|PubMed:24245781}. |
| Q8IXQ6 | PARP9 | Y495 | ochoa | Protein mono-ADP-ribosyltransferase PARP9 (EC 2.4.2.-) (ADP-ribosyltransferase diphtheria toxin-like 9) (ARTD9) (B aggressive lymphoma protein) (Poly [ADP-ribose] polymerase 9) (PARP-9) | ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses (PubMed:16809771, PubMed:23230272, PubMed:26479788, PubMed:27796300). Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) (PubMed:28525742). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones (PubMed:28525742). During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (PubMed:23230272). Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272, PubMed:28525742). In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ); the complex function is negatively modulated by PARP9 activity (PubMed:28525742). Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (By similarity). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation (PubMed:27796300). Also suppresses PARP14-mediated STAT6 ADP-ribosylation (PubMed:27796300). {ECO:0000250|UniProtKB:Q8CAS9, ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28525742}. |
| Q8IY22 | CMIP | Y752 | ochoa | C-Maf-inducing protein (c-Mip) (Truncated c-Maf-inducing protein) (Tc-Mip) | Plays a role in T-cell signaling pathway. Isoform 2 may play a role in T-helper 2 (Th2) signaling pathway and seems to represent the first proximal signaling protein that links T-cell receptor-mediated signal to the activation of c-Maf Th2 specific factor. {ECO:0000269|PubMed:12939343, ECO:0000269|PubMed:15128042}. |
| Q8IZ21 | PHACTR4 | Y647 | ochoa | Phosphatase and actin regulator 4 | Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway (By similarity). {ECO:0000250}. |
| Q8N3F8 | MICALL1 | Y203 | ochoa | MICAL-like protein 1 (Molecule interacting with Rab13) (MIRab13) | Lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, acts as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation (PubMed:19864458, PubMed:20801876, PubMed:23596323, PubMed:34100897). Involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking (PubMed:21795389). Alternatively, regulates slow endocytic recycling of endocytosed proteins back to the plasma membrane (PubMed:19864458). Also involved in cargo protein delivery to the plasma membrane (PubMed:34100897). Plays a role in ciliogenesis coordination, recruits EHD1 to primary cilium where it is anchored to the centriole through interaction with tubulins (PubMed:31615969). May indirectly play a role in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q8BGT6, ECO:0000269|PubMed:19864458, ECO:0000269|PubMed:20801876, ECO:0000269|PubMed:21795389, ECO:0000269|PubMed:23596323, ECO:0000269|PubMed:31615969, ECO:0000269|PubMed:34100897}. |
| Q8N4C8 | MINK1 | Y987 | ochoa | Misshapen-like kinase 1 (EC 2.7.11.1) (GCK family kinase MiNK) (MAPK/ERK kinase kinase kinase 6) (MEK kinase kinase 6) (MEKKK 6) (Misshapen/NIK-related kinase) (Mitogen-activated protein kinase kinase kinase kinase 6) | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking (PubMed:10708748, PubMed:16337592). Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons (By similarity). Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1 (PubMed:18930710, PubMed:21690388). Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1 (By similarity). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000250|UniProtKB:F1LP90, ECO:0000250|UniProtKB:Q9JM52, ECO:0000269|PubMed:10708748, ECO:0000269|PubMed:16337592, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. |
| Q8N4X5 | AFAP1L2 | Y307 | ochoa | Actin filament-associated protein 1-like 2 (AFAP1-like protein 2) | May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269|PubMed:17412687}. |
| Q8N4X5 | AFAP1L2 | Y359 | ochoa | Actin filament-associated protein 1-like 2 (AFAP1-like protein 2) | May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269|PubMed:17412687}. |
| Q8N6P7 | IL22RA1 | Y251 | psp | Interleukin-22 receptor subunit alpha-1 (IL-22 receptor subunit alpha-1) (IL-22R-alpha-1) (IL-22RA1) (Cytokine receptor class-II member 9) (Cytokine receptor family 2 member 9) (CRF2-9) (ZcytoR11) | Component of the receptor for IL20, IL22 and IL24. Component of IL22 receptor formed by IL22RA1 and IL10RB enabling IL22 signaling via JAK/STAT pathways. IL22 also induces activation of MAPK1/MAPK3 and Akt kinases pathways. Component of one of the receptor for IL20 and IL24 formed by IL22RA1 and IL20RB also signaling through STATs activation. Mediates IL24 antiangiogenic activity as well as IL24 inhibitory effect on endothelial cell tube formation and differentiation. {ECO:0000269|PubMed:11035029, ECO:0000269|PubMed:11564763, ECO:0000269|PubMed:11706020, ECO:0000269|PubMed:12351624, ECO:0000269|PubMed:12941841, ECO:0000269|PubMed:17204547}. |
| Q8NAF0 | ZNF579 | Y57 | ochoa | Zinc finger protein 579 | May be involved in transcriptional regulation. |
| Q8ND04 | SMG8 | Y309 | ochoa | Nonsense-mediated mRNA decay factor SMG8 (Amplified in breast cancer gene 2 protein) (Protein smg-8 homolog) | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG9 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required to mediate the recruitment of SMG1 to the ribosome:SURF complex and to suppress SMG1 kinase activity until the ribosome:SURF complex locates the exon junction complex (EJC). Acts as a regulator of kinase activity. {ECO:0000269|PubMed:19417104}. |
| Q8NF50 | DOCK8 | Y1285 | ochoa | Dedicator of cytokinesis protein 8 | Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:22461490, PubMed:28028151). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (By similarity). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing (PubMed:25762780). {ECO:0000250|UniProtKB:Q8C147, ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:25762780, ECO:0000269|PubMed:28028151}. |
| Q8NG06 | TRIM58 | Y392 | psp | E3 ubiquitin-protein ligase TRIM58 (EC 2.3.2.27) (Protein BIA2) (RING-type E3 ubiquitin transferase TRIM58) (Tripartite motif-containing protein 58) | E3 ubiquitin ligase induced during late erythropoiesis. Directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. May participate in the erythroblast enucleation process through regulation of nuclear polarization. {ECO:0000269|PubMed:25241935}. |
| Q8TDX7 | NEK7 | Y201 | ochoa | Serine/threonine-protein kinase Nek7 (EC 2.7.11.34) (Never in mitosis A-related kinase 7) (NimA-related protein kinase 7) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:19941817, PubMed:31409757). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:19941817, PubMed:26522158, PubMed:31409757). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502, PubMed:39173637). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502, PubMed:39173637). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953). {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132, ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158, ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:31409757, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637}. |
| Q8TF62 | ATP8B4 | Y1164 | ochoa | Probable phospholipid-transporting ATPase IM (EC 7.6.2.1) (ATPase class I type 8B member 4) (P4-ATPase flippase complex alpha subunit ATP8B4) | Component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules (Probable). {ECO:0000305}. |
| Q8WVP7 | LMBR1 | Y32 | ochoa | Limb region 1 protein homolog (Differentiation-related gene 14 protein) | Putative membrane receptor. |
| Q8WVP7 | LMBR1 | Y36 | ochoa | Limb region 1 protein homolog (Differentiation-related gene 14 protein) | Putative membrane receptor. |
| Q8WYB5 | KAT6B | Y878 | psp | Histone acetyltransferase KAT6B (EC 2.3.1.48) (Histone acetyltransferase MOZ2) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4) (MYST-4) (Monocytic leukemia zinc finger protein-related factor) | Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. {ECO:0000269|PubMed:10497217, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:16387653}. |
| Q92523 | CPT1B | Y449 | ochoa | Carnitine O-palmitoyltransferase 1, muscle isoform (CPT1-M) (EC 2.3.1.21) (Carnitine O-palmitoyltransferase I, muscle isoform) (CPT I) (CPTI-M) (Carnitine palmitoyltransferase 1B) (Carnitine palmitoyltransferase I-like protein) | Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. {ECO:0000250|UniProtKB:Q63704}. |
| Q92556 | ELMO1 | Y48 | psp | Engulfment and cell motility protein 1 (Protein ced-12 homolog) | Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1. {ECO:0000269|PubMed:11595183, ECO:0000269|PubMed:12134158}. |
| Q92785 | DPF2 | Y172 | ochoa | Zinc finger protein ubi-d4 (Apoptosis response zinc finger protein) (BRG1-associated factor 45D) (BAF45D) (D4, zinc and double PHD fingers family 2) (Protein requiem) | Plays an active role in transcriptional regulation by binding modified histones H3 and H4 (PubMed:27775714, PubMed:28533407). Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells (PubMed:28533407). Might also have a role in the development and maturation of lymphoid cells (By similarity). Involved in the regulation of non-canonical NF-kappa-B pathway (PubMed:20460684). {ECO:0000250|UniProtKB:Q61103, ECO:0000269|PubMed:20460684, ECO:0000269|PubMed:27775714, ECO:0000269|PubMed:28533407}. |
| Q92793 | CREBBP | Y659 | psp | CREB-binding protein (Histone lysine acetyltransferase CREBBP) (EC 2.3.1.48) (Protein lactyltransferas CREBBP) (EC 2.3.1.-) (Protein-lysine acetyltransferase CREBBP) (EC 2.3.1.-) | Acetylates histones, giving a specific tag for transcriptional activation (PubMed:21131905, PubMed:24616510). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:24207024, PubMed:28790157, PubMed:30540930, PubMed:35675826, PubMed:9707565). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as lactoyl-CoA, and is able to mediate protein lactylation (PubMed:38128537). Catalyzes lactylation of MRE11 in response to DNA damage, thereby promoting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38128537). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:35675826, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9707565}. |
| Q92995 | USP13 | Y708 | psp | Ubiquitin carboxyl-terminal hydrolase 13 (EC 3.4.19.12) (Deubiquitinating enzyme 13) (Isopeptidase T-3) (ISOT-3) (Ubiquitin thioesterase 13) (Ubiquitin-specific-processing protease 13) | Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response (PubMed:21571647, PubMed:32772043, PubMed:33592542). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy (PubMed:32101753). Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB (PubMed:32772043). In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1 (PubMed:33592542). Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion (PubMed:36585612). Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1 (PubMed:23940278, PubMed:28534493). {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:32101753, ECO:0000269|PubMed:32772043, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:36585612}. |
| Q96A65 | EXOC4 | Y247 | ochoa | Exocyst complex component 4 (Exocyst complex component Sec8) | Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. {ECO:0000250|UniProtKB:Q62824}. |
| Q96AE4 | FUBP1 | Y58 | ochoa|psp | Far upstream element-binding protein 1 (FBP) (FUSE-binding protein 1) (DNA helicase V) (hDH V) | Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription. {ECO:0000269|PubMed:8125259}. |
| Q96B67 | ARRDC3 | Y394 | ochoa | Arrestin domain-containing protein 3 (TBP-2-like inducible membrane protein) (TLIMP) | Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors (PubMed:20559325, PubMed:21982743, PubMed:23208550). Plays a role in NEDD4-mediated ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2 degradation (PubMed:20559325, PubMed:23208550). May recruit NEDD4 to ADRB2 (PubMed:20559325). Alternatively, may function as adapter protein that does not play a major role in recruiting NEDD4 to ADRB2, but rather plays a role in a targeting ADRB2 to endosomes (PubMed:23208550). {ECO:0000269|PubMed:20559325, ECO:0000269|PubMed:23208550}. |
| Q96BY6 | DOCK10 | Y1854 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96DL1 | NXPE2 | Y155 | ochoa | NXPE family member 2 (Protein FAM55B) | None |
| Q96FC9 | DDX11 | Y202 | ochoa | ATP-dependent DNA helicase DDX11 (EC 5.6.2.3) (CHL1-related protein 1) (hCHLR1) (DEAD/H-box protein 11) (DNA 5'-3' helicase DDX11) (Keratinocyte growth factor-regulated gene 2 protein) (KRG-2) | DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis (PubMed:10648783, PubMed:21854770, PubMed:23797032, PubMed:26089203, PubMed:26503245). Its double-stranded DNA helicase activity requires either a minimal 5'-single-stranded tail length of approximately 15 nt (flap substrates) or 10 nt length single-stranded gapped DNA substrates of a partial duplex DNA structure for helicase loading and translocation along DNA in a 5' to 3' direction (PubMed:10648783, PubMed:18499658, PubMed:22102414). The helicase activity is capable of displacing duplex regions up to 100 bp, which can be extended up to 500 bp by the replication protein A (RPA) or the cohesion CTF18-replication factor C (Ctf18-RFC) complex activities (PubMed:18499658). Also shows ATPase- and helicase activities on substrates that mimic key DNA intermediates of replication, repair and homologous recombination reactions, including forked duplex, anti-parallel G-quadruplex and three-stranded D-loop DNA molecules (PubMed:22102414, PubMed:26503245). Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage (PubMed:23797032). Recruited with TIMELESS factor upon DNA-replication stress response at DNA replication fork to preserve replication fork progression, and hence ensure DNA replication fidelity (PubMed:26503245). Also cooperates with TIMELESS factor during DNA replication to regulate proper sister chromatid cohesion and mitotic chromosome segregation (PubMed:17105772, PubMed:18499658, PubMed:20124417, PubMed:23116066, PubMed:23797032). Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner; and hence it may contribute in Okazaki fragment processing at DNA replication fork during lagging strand DNA synthesis (PubMed:18499658). Its ability to function at DNA replication fork is modulated by its binding to long non-coding RNA (lncRNA) cohesion regulator non-coding RNA DDX11-AS1/CONCR, which is able to increase both DDX11 ATPase activity and binding to DNA replicating regions (PubMed:27477908). Also plays a role in heterochromatin organization (PubMed:21854770). Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (PubMed:26089203). Plays a role in embryonic development and prevention of aneuploidy (By similarity). Involved in melanoma cell proliferation and survival (PubMed:23116066). Associates with chromatin at DNA replication fork regions (PubMed:27477908). Binds to single- and double-stranded DNAs (PubMed:18499658, PubMed:22102414, PubMed:9013641). {ECO:0000250|UniProtKB:Q6AXC6, ECO:0000269|PubMed:10648783, ECO:0000269|PubMed:17105772, ECO:0000269|PubMed:18499658, ECO:0000269|PubMed:20124417, ECO:0000269|PubMed:21854770, ECO:0000269|PubMed:22102414, ECO:0000269|PubMed:23116066, ECO:0000269|PubMed:23797032, ECO:0000269|PubMed:26089203, ECO:0000269|PubMed:26503245, ECO:0000269|PubMed:27477908}.; FUNCTION: (Microbial infection) Required for bovine papillomavirus type 1 regulatory protein E2 loading onto mitotic chromosomes during DNA replication for the viral genome to be maintained and segregated. {ECO:0000269|PubMed:17189189}. |
| Q96II8 | LRCH3 | Y490 | ochoa | DISP complex protein LRCH3 (Leucine-rich repeat and calponin homology domain-containing protein 3) | As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. {ECO:0000269|PubMed:29467281}. |
| Q96J84 | KIRREL1 | Y721 | ochoa | Kin of IRRE-like protein 1 (Kin of irregular chiasm-like protein 1) (Nephrin-like protein 1) | Required for proper function of the glomerular filtration barrier. It is involved in the maintenance of a stable podocyte architecture with interdigitating foot processes connected by specialized cell-cell junctions, known as the slit diaphragm (PubMed:31472902). It is a signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:31472902}. |
| Q96JB2 | COG3 | Y407 | ochoa | Conserved oligomeric Golgi complex subunit 3 (COG complex subunit 3) (Component of oligomeric Golgi complex 3) (Vesicle-docking protein SEC34 homolog) (p94) | Involved in ER-Golgi transport (PubMed:11929878). Also involved in retrograde (Golgi to ER) transport (PubMed:37711075). {ECO:0000269|PubMed:11929878, ECO:0000269|PubMed:37711075}. |
| Q96JJ3 | ELMO2 | Y48 | ochoa | Engulfment and cell motility protein 2 (Protein ced-12 homolog A) (hCed-12A) | Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1. {ECO:0000269|PubMed:11595183, ECO:0000269|PubMed:11703939, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:27476657}. |
| Q96L92 | SNX27 | Y346 | ochoa | Sorting nexin-27 | Involved in the retrograde transport from endosome to plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins. Following internalization, endocytosed transmembrane proteins are delivered to early endosomes and recycled to the plasma membrane instead of being degraded in lysosomes. SNX27 specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C-terminus: following interaction with target transmembrane proteins, associates with the retromer complex, preventing entry into the lysosomal pathway, and promotes retromer-tubule based plasma membrane recycling. SNX27 also binds with the WASH complex. Interacts with membranes containing phosphatidylinositol-3-phosphate (PtdIns(3P)). May participate in establishment of natural killer cell polarity. Recruits CYTIP to early endosomes. {ECO:0000269|PubMed:17351151, ECO:0000269|PubMed:20733053, ECO:0000269|PubMed:21300787, ECO:0000269|PubMed:21303929, ECO:0000269|PubMed:21602791, ECO:0000269|PubMed:21926430, ECO:0000269|PubMed:22411990, ECO:0000269|PubMed:23563491}. |
| Q96L93 | KIF16B | Y1079 | ochoa | Kinesin-like protein KIF16B (Sorting nexin-23) | Plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation. Regulates the plus end motility of early endosomes and the balance between recycling and degradation of receptors such as EGF receptor (EGFR) and FGF receptor (FGFR). Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. {ECO:0000269|PubMed:15882625}. |
| Q96Q40 | CDK15 | Y114 | ochoa | Cyclin-dependent kinase 15 (EC 2.7.11.22) (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein) (Cell division protein kinase 15) (Serine/threonine-protein kinase ALS2CR7) (Serine/threonine-protein kinase PFTAIRE-2) | Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at 'Thr-34'. {ECO:0000269|PubMed:24866247}. |
| Q96T37 | RBM15 | Y546 | ochoa | RNA-binding protein 15 (One-twenty two protein 1) (RNA-binding motif protein 15) | RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:27602518). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (By similarity). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (PubMed:27602518). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (By similarity). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (PubMed:26575292). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (By similarity). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (By similarity). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (PubMed:17001072, PubMed:19786495). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (PubMed:17001072, PubMed:19786495). May be implicated in HOX gene regulation (PubMed:11344311). {ECO:0000250|UniProtKB:Q0VBL3, ECO:0000269|PubMed:17001072, ECO:0000269|PubMed:19786495, ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:27602518, ECO:0000305|PubMed:11344311}. |
| Q99504 | EYA3 | Y237 | psp | Protein phosphatase EYA3 (EC 3.1.3.48) (Eyes absent homolog 3) | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye. {ECO:0000250|UniProtKB:P97480, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884}. |
| Q99541 | PLIN2 | Y232 | psp | Perilipin-2 (Adipophilin) (Adipose differentiation-related protein) (ADRP) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets. {ECO:0000269|PubMed:34077757}. |
| Q99650 | OSMR | Y837 | ochoa|psp | Oncostatin-M-specific receptor subunit beta (Interleukin-31 receptor subunit beta) (IL-31 receptor subunit beta) (IL-31R subunit beta) (IL-31R-beta) (IL-31RB) | Associates with IL31RA to form the IL31 receptor. Binds IL31 to activate STAT3 and possibly STAT1 and STAT5. Capable of transducing OSM-specific signaling events. {ECO:0000269|PubMed:15184896, ECO:0000269|PubMed:8999038}. |
| Q99704 | DOK1 | Y146 | psp | Docking protein 1 (Downstream of tyrosine kinase 1) (p62(dok)) (pp62) | DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3. {ECO:0000269|PubMed:18156175}. |
| Q99959 | PKP2 | Y261 | ochoa | Plakophilin-2 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297). {ECO:0000250|UniProtKB:F1M7L9, ECO:0000250|UniProtKB:Q9CQ73, ECO:0000269|PubMed:18662195, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:22781308, ECO:0000269|PubMed:23884246, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:28169297, ECO:0000269|PubMed:34368962, ECO:0000269|PubMed:35959657}. |
| Q9BQ90 | KLHDC3 | Y193 | ochoa | Kelch domain-containing protein 3 (Testis intracellular mediator protein) | Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29775578, PubMed:29779948). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29775578, PubMed:29779948). The CRL2(KLHDC3) complex specifically recognizes proteins with a glycine (Gly) at the C-terminus, leading to their ubiquitination and degradation: recognizes the C-terminal -Arg-(Xaa)n-Arg-Gly, -Arg-(Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly degrons (PubMed:29775578, PubMed:29779948). The CRL2(KLHDC3) complex mediates ubiquitination and degradation of truncated SELENOV and SEPHS2 selenoproteins produced by failed UGA/Sec decoding, which end with a glycine (PubMed:26138980). May be involved in meiotic recombination process (PubMed:12606021). {ECO:0000269|PubMed:12606021, ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:29779948}. |
| Q9BQE3 | TUBA1C | Y224 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9BTC0 | DIDO1 | Y1700 | 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}. |
| Q9BUB5 | MKNK1 | Y60 | ochoa | MAP kinase-interacting serine/threonine-protein kinase 1 (EC 2.7.11.1) (MAP kinase signal-integrating kinase 1) (MAPK signal-integrating kinase 1) (Mnk1) | May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. {ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:15350534, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9878069}. |
| Q9BVA1 | TUBB2B | Y222 | ochoa | Tubulin beta-2B chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:23001566, PubMed:26732629, PubMed:28013290). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910). {ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:23001566, ECO:0000269|PubMed:26732629, ECO:0000269|PubMed:28013290}. |
| Q9BWW4 | SSBP3 | Y25 | psp | Single-stranded DNA-binding protein 3 (Sequence-specific single-stranded-DNA-binding protein) | May be involved in transcription regulation of the alpha 2(I) collagen gene where it binds to the single-stranded polypyrimidine sequences in the promoter region. {ECO:0000250}. |
| Q9C0B0 | UNK | Y412 | ochoa | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9GZV5 | WWTR1 | Y305 | psp | WW domain-containing transcription regulator protein 1 (Transcriptional coactivator with PDZ-binding motif) | Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:11118213, PubMed:18227151, PubMed:23911299). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18227151). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (PubMed:19010321). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (PubMed:18568018). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (PubMed:18227151, PubMed:18568018). {ECO:0000269|PubMed:11118213, ECO:0000269|PubMed:18227151, ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:19010321, ECO:0000269|PubMed:23911299}. |
| Q9H008 | LHPP | Y158 | ochoa | Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (hLHPP) (EC 3.1.3.-) (EC 3.6.1.1) | Phosphatase that hydrolyzes imidodiphosphate, 3-phosphohistidine and 6-phospholysine. Has broad substrate specificity and can also hydrolyze inorganic diphosphate, but with lower efficiency (By similarity). {ECO:0000250}. |
| Q9H1Y3 | OPN3 | Y140 | psp | Opsin-3 (Encephalopsin) (Panopsin) | G-protein coupled receptor which selectively activates G proteins via ultraviolet A (UVA) light-mediated activation in the skin (PubMed:28842328, PubMed:31097585, PubMed:31380578). Binds both 11-cis retinal and all-trans retinal (PubMed:31097585). Regulates melanogenesis in melanocytes via inhibition of alpha-MSH-induced MC1R-mediated cAMP signaling, modulation of calcium flux, regulation of CAMK2 phosphorylation, and subsequently phosphorylation of CREB, p38, ERK and MITF in response to blue light (PubMed:28842328, PubMed:31097585). Plays a role in melanocyte survival through regulation of intracellular calcium levels and subsequent BCL2/RAF1 signaling (PubMed:31730232). Additionally regulates apoptosis via cytochrome c release and subsequent activation of the caspase cascade (PubMed:31730232). Required for TYR and DCT blue light-induced complex formation in melanocytes (PubMed:28842328). Involved in keratinocyte differentiation in response to blue-light (PubMed:30168605). Required for the UVA-mediated induction of calcium and mitogen-activated protein kinase signaling resulting in the expression of MMP1, MMP2, MMP3, MMP9 and TIMP1 in dermal fibroblasts (PubMed:31380578). Plays a role in light-mediated glucose uptake, mitochondrial respiration and fatty acid metabolism in brown adipocyte tissues (By similarity). May be involved in photorelaxation of airway smooth muscle cells, via blue-light dependent GPCR signaling pathways (By similarity). {ECO:0000250|UniProtKB:Q9WUK7, ECO:0000269|PubMed:28842328, ECO:0000269|PubMed:30168605, ECO:0000269|PubMed:31097585, ECO:0000269|PubMed:31380578, ECO:0000269|PubMed:31730232}. |
| Q9H204 | MED28 | Y64 | psp | Mediator of RNA polymerase II transcription subunit 28 (Endothelial-derived protein 1) (Mediator complex subunit 28) (Merlin and Grb2-interacting cytoskeletal protein) (Magicin) (Tumor angiogenesis marker EG-1) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May be part of a complex containing NF2/merlin that participates in cellular signaling to the actin cytoskeleton downstream of tyrosine kinase signaling pathways. {ECO:0000269|PubMed:15467741}. |
| Q9H3R0 | KDM4C | Y201 | ochoa | Lysine-specific demethylase 4C (EC 1.14.11.66) (Gene amplified in squamous cell carcinoma 1 protein) (GASC-1 protein) (JmjC domain-containing histone demethylation protein 3C) (Jumonji domain-containing protein 2C) ([histone H3]-trimethyl-L-lysine(9) demethylase 4C) | Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}. |
| Q9H6B4 | CLMP | Y333 | ochoa | CXADR-like membrane protein (Adipocyte adhesion molecule) (Coxsackie- and adenovirus receptor-like membrane protein) (CAR-like membrane protein) | May be involved in the cell-cell adhesion. May play a role in adipocyte differentiation and development of obesity. Is required for normal small intestine development. {ECO:0000269|PubMed:14573622, ECO:0000269|PubMed:15563274, ECO:0000269|PubMed:22155368}. |
| Q9H706 | GAREM1 | Y74 | ochoa | GRB2-associated and regulator of MAPK protein 1 (GRB2-associated and regulator of MAPK1) | [Isoform 1]: Acts as an adapter protein that plays a role in intracellular signaling cascades triggered either by the cell surface activated epidermal growth factor receptor and/or cytoplasmic protein tyrosine kinases. Promotes activation of the MAPK/ERK signaling pathway. Plays a role in the regulation of cell proliferation. {ECO:0000269|PubMed:19509291}. |
| Q9H792 | PEAK1 | Y1215 | ochoa | Inactive tyrosine-protein kinase PEAK1 (Pseudopodium-enriched atypical kinase 1) (Sugen kinase 269) (Tyrosine-protein kinase SgK269) | Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics (PubMed:20534451, PubMed:23105102, PubMed:35687021). Acts as a scaffold for mediating EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654, ECO:0000269|PubMed:35687021}. |
| Q9H9R9 | DBNDD1 | Y116 | ochoa | Dysbindin domain-containing protein 1 | None |
| Q9HCK1 | ZDBF2 | Y531 | ochoa | DBF4-type zinc finger-containing protein 2 | None |
| Q9HCK8 | CHD8 | Y2208 | ochoa | Chromodomain-helicase-DNA-binding protein 8 (CHD-8) (EC 3.6.4.-) (ATP-dependent helicase CHD8) (Helicase with SNF2 domain 1) | ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL. {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692, ECO:0000269|PubMed:28533432, ECO:0000269|PubMed:36537238}. |
| Q9NQ84 | GPRC5C | Y370 | ochoa | G-protein coupled receptor family C group 5 member C (Retinoic acid-induced gene 3 protein) (RAIG-3) | This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways. {ECO:0000250}. |
| Q9NQU5 | PAK6 | Y566 | psp | Serine/threonine-protein kinase PAK 6 (EC 2.7.11.1) (PAK-5) (p21-activated kinase 6) (PAK-6) | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Also inhibits ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}. |
| Q9NQW8 | CNGB3 | Y545 | psp | Cyclic nucleotide-gated channel beta-3 (CNG channel beta-3) (Cone photoreceptor cGMP-gated channel subunit beta) (Cyclic nucleotide-gated cation channel beta-3) (Cyclic nucleotide-gated cation channel modulatory subunit) | Pore-forming subunit of the cone cyclic nucleotide-gated channel. Mediates cone photoresponses at bright light converting transient changes in intracellular cGMP levels into electrical signals. In the dark, cGMP levels are high and keep the channel open enabling a steady inward current carried by Na(+) and Ca(2+) ions that leads to membrane depolarization and neurotransmitter release from synaptic terminals. Upon photon absorption cGMP levels decline leading to channel closure and membrane hyperpolarization that ultimately slows neurotransmitter release and signals the presence of light, the end point of the phototransduction cascade. Conducts cGMP- and cAMP-gated ion currents, with permeability for monovalent and divalent cations. {ECO:0000269|PubMed:10888875, ECO:0000269|PubMed:12815043, ECO:0000269|PubMed:34969976, ECO:0000269|PubMed:37463923}. |
| Q9NTG7 | SIRT3 | Y226 | psp | NAD-dependent protein deacetylase sirtuin-3, mitochondrial (hSIRT3) (EC 2.3.1.286) (NAD-dependent protein delactylase sirtuin-3) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 3) (SIR2-like protein 3) | NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:19535340, PubMed:23283301, PubMed:24121500, PubMed:24252090). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090, PubMed:38146092). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA, MRPL12 and the ATP synthase subunit ATP5PO (PubMed:16788062, PubMed:18680753, PubMed:19535340, PubMed:24121500, PubMed:24252090, PubMed:38146092). Contributes to the regulation of the cellular energy metabolism (PubMed:24252090). Important for regulating tissue-specific ATP levels (PubMed:18794531). In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription (PubMed:23283301). Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation (By similarity). Regulates hepatic lipogenesis (By similarity). Uses NAD(+) substrate imported by SLC25A47, triggering downstream activation of PRKAA1/AMPK-alpha signaling cascade that ultimately downregulates sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance (By similarity). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating delactylation of proteins, such as CCNE2 and 'Lys-16' of histone H4 (H4K16la) (PubMed:36896611, PubMed:37720100). {ECO:0000250|UniProtKB:Q8R104, ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852, ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:24121500, ECO:0000269|PubMed:24252090, ECO:0000269|PubMed:36896611, ECO:0000269|PubMed:37720100, ECO:0000269|PubMed:38146092}. |
| Q9NTZ6 | RBM12 | Y526 | ochoa | RNA-binding protein 12 (RNA-binding motif protein 12) (SH3/WW domain anchor protein in the nucleus) (SWAN) | None |
| Q9NV06 | DCAF13 | Y401 | ochoa | DDB1- and CUL4-associated factor 13 (WD repeat and SOF domain-containing protein 1) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Participates in the 18S rRNA processing in growing oocytes, being essential for oocyte nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) transition (PubMed:30283081). {ECO:0000269|PubMed:30283081, ECO:0000269|PubMed:34516797}.; FUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that plays a key role in embryo preimplantation and is required for normal meiotic cycle progression in oocytes (PubMed:16949367, PubMed:30111536, PubMed:31492966). Acts as a maternal factor that regulates oocyte and zygotic chromatin tightness during maternal to zygotic transition (By similarity). Also involved in the transformation of the endometrium into the decidua, known as decidualization, providing a solid foundation for implantation of blastocysts (PubMed:35932979). Recognizes the histone methyltransferases SUV39H1 and SUV39H2 and directs them to polyubiquitination and proteasomal degradation, which facilitates the H3K9me3 removal and early zygotic gene expression, essential steps for progressive genome reprogramming and the establishment of pluripotency during preimplantation embryonic development (PubMed:30111536). Supports the spindle assembly and chromosome condensation during oocyte meiotic division by targeting the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation (PubMed:31492966). Targets PMP22 for polyubiquitination and proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:Q6PAC3, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:30111536, ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:35932979}. |
| Q9NVU0 | POLR3E | Y26 | ochoa | DNA-directed RNA polymerase III subunit RPC5 (RNA polymerase III subunit C5) (DNA-directed RNA polymerase III 80 kDa polypeptide) | DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:12391170, PubMed:20413673, PubMed:35637192). Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Assembles with POLR3D/RPC4 forming a subcomplex that binds the Pol III core. Enables recruitment of Pol III at transcription initiation site and drives transcription initiation from both type 2 and type 3 DNA promoters. Required for efficient transcription termination and reinitiation (By similarity) (PubMed:12391170, PubMed:20413673, PubMed:35637192). Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway (PubMed:19609254, PubMed:19631370). {ECO:0000250|UniProtKB:P36121, ECO:0000269|PubMed:12391170, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20413673, ECO:0000269|PubMed:35637192}. |
| Q9NVU0 | POLR3E | Y30 | ochoa | DNA-directed RNA polymerase III subunit RPC5 (RNA polymerase III subunit C5) (DNA-directed RNA polymerase III 80 kDa polypeptide) | DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:12391170, PubMed:20413673, PubMed:35637192). Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Assembles with POLR3D/RPC4 forming a subcomplex that binds the Pol III core. Enables recruitment of Pol III at transcription initiation site and drives transcription initiation from both type 2 and type 3 DNA promoters. Required for efficient transcription termination and reinitiation (By similarity) (PubMed:12391170, PubMed:20413673, PubMed:35637192). Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway (PubMed:19609254, PubMed:19631370). {ECO:0000250|UniProtKB:P36121, ECO:0000269|PubMed:12391170, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20413673, ECO:0000269|PubMed:35637192}. |
| Q9NVX0 | HAUS2 | Y210 | ochoa | HAUS augmin-like complex subunit 2 (Centrosomal protein of 27 kDa) (Cep27) | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. {ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q9NY65 | TUBA8 | Y224 | ochoa | Tubulin alpha-8 chain (EC 3.6.5.-) (Alpha-tubulin 8) (Tubulin alpha chain-like 2) [Cleaved into: Dephenylalaninated tubulin alpha-8 chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9P0J1 | PDP1 | Y94 | psp | [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial (PDP 1) (EC 3.1.3.43) (Protein phosphatase 2C) (Pyruvate dehydrogenase phosphatase catalytic subunit 1) (PDPC 1) | Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA. {ECO:0000269|PubMed:15554715, ECO:0000305|PubMed:15855260}. |
| Q9P0J1 | PDP1 | Y381 | psp | [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial (PDP 1) (EC 3.1.3.43) (Protein phosphatase 2C) (Pyruvate dehydrogenase phosphatase catalytic subunit 1) (PDPC 1) | Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA. {ECO:0000269|PubMed:15554715, ECO:0000305|PubMed:15855260}. |
| Q9UBP9 | GULP1 | Y77 | psp | PTB domain-containing engulfment adapter protein 1 (Cell death protein 6 homolog) (PTB domain adapter protein CED-6) (Protein GULP) | May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. Modulates cellular glycosphingolipid and cholesterol transport. May play a role in the internalization and endosomal trafficking of various LRP1 ligands, such as PSAP. Increases cellular levels of GTP-bound ARF6. {ECO:0000269|PubMed:10574763, ECO:0000269|PubMed:10574771, ECO:0000269|PubMed:16497666, ECO:0000269|PubMed:17398097}. |
| Q9UGK3 | STAP2 | Y22 | psp | Signal-transducing adaptor protein 2 (STAP-2) (Breast tumor kinase substrate) (BRK substrate) | Substrate of protein kinase PTK6. May play a regulatory role in the acute-phase response in systemic inflammation and may modulate STAT3 activity. {ECO:0000269|PubMed:10980601}. |
| Q9UGK3 | STAP2 | Y250 | ochoa|psp | Signal-transducing adaptor protein 2 (STAP-2) (Breast tumor kinase substrate) (BRK substrate) | Substrate of protein kinase PTK6. May play a regulatory role in the acute-phase response in systemic inflammation and may modulate STAT3 activity. {ECO:0000269|PubMed:10980601}. |
| Q9UGP4 | LIMD1 | Y179 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UK17 | KCND3 | Y108 | psp | A-type voltage-gated potassium channel KCND3 (Potassium voltage-gated channel subfamily D member 3) (Voltage-gated potassium channel subunit Kv4.3) | Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). In cardiomyocytes, may generate the transient outward potassium current I(To) (By similarity). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). Channel properties are modulated by interactions with regulatory subunits (PubMed:17187064, PubMed:34997220). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:17187064, PubMed:34997220). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (PubMed:34997220). {ECO:0000250|UniProtKB:Q62897, ECO:0000269|PubMed:10200233, ECO:0000269|PubMed:17187064, ECO:0000269|PubMed:21349352, ECO:0000269|PubMed:22457051, ECO:0000269|PubMed:23280837, ECO:0000269|PubMed:23280838, ECO:0000269|PubMed:34997220, ECO:0000269|PubMed:9843794}. |
| Q9UKW4 | VAV3 | Y164 | psp | Guanine nucleotide exchange factor VAV3 (VAV-3) | Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1. Binds physically to the nucleotide-free states of those GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). May be important for integrin-mediated signaling, at least in some cell types. In osteoclasts, along with SYK tyrosine kinase, required for signaling through integrin alpha-v/beta-1 (ITAGV-ITGB1), a crucial event for osteoclast proper cytoskeleton organization and function. This signaling pathway involves RAC1, but not RHO, activation. Necessary for proper wound healing. In the course of wound healing, required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Responsible for integrin beta-2 (ITGB2)-mediated macrophage adhesion and, to a lesser extent, contributes to beta-3 (ITGB3)-mediated adhesion. Does not affect integrin beta-1 (ITGB1)-mediated adhesion (By similarity). {ECO:0000250}. |
| Q9ULZ3 | PYCARD | Y137 | psp | Apoptosis-associated speck-like protein containing a CARD (hASC) (Caspase recruitment domain-containing protein 5) (PYD and CARD domain-containing protein) (Target of methylation-induced silencing 1) | Functions as a key mediator in apoptosis and inflammation (PubMed:11103777, PubMed:12646168, PubMed:15030775, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMed:19494289, PubMed:21487011, PubMed:24630722, PubMed:25847972, PubMed:30674671, PubMed:34678144, PubMed:36050480). Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner (PubMed:11103777, PubMed:12646168). Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3 (PubMed:14730312, PubMed:16964285). Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes (NLRP1, NLRP2, NLRP3, NLRP6, AIM2 and probably IFI16) which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:15030775, PubMed:16982856, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMed:21487011, PubMed:23530044, PubMed:24630722, PubMed:25847972, PubMed:29440442, PubMed:30674671, PubMed:33980849, PubMed:34678144, PubMed:34706239). Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death (PubMed:24630722). The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions (PubMed:14499617, PubMed:19234215, PubMed:24630722). Clustered PYCARD nucleates the formation of caspase-1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization (PubMed:24630722). In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1 (PubMed:17349957). In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation (PubMed:16964285). May be involved in RIGI-triggered pro-inflammatory responses and inflammasome activation (PubMed:19915568). In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8 (PubMed:19158675, PubMed:19158676). In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form (PubMed:22732093). Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways (PubMed:12486103, PubMed:16585594). For regulation of NF-kappa-B activating and inhibiting functions have been reported (PubMed:12486103). Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK (PubMed:12486103, PubMed:16585594). Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing (PubMed:16585594). Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590). {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:19915568, ECO:0000269|PubMed:21487011, ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:23530044, ECO:0000269|PubMed:24630722, ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:33980849, ECO:0000269|PubMed:34678144, ECO:0000269|PubMed:34706239, ECO:0000269|PubMed:36050480}.; FUNCTION: [Isoform 2]: May have a regulating effect on the function as inflammasome adapter. {ECO:0000269|PubMed:19759850, ECO:0000269|PubMed:20482797}.; FUNCTION: [Isoform 3]: Seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. {ECO:0000269|PubMed:20482797}. |
| Q9ULZ3 | PYCARD | Y146 | psp | Apoptosis-associated speck-like protein containing a CARD (hASC) (Caspase recruitment domain-containing protein 5) (PYD and CARD domain-containing protein) (Target of methylation-induced silencing 1) | Functions as a key mediator in apoptosis and inflammation (PubMed:11103777, PubMed:12646168, PubMed:15030775, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMed:19494289, PubMed:21487011, PubMed:24630722, PubMed:25847972, PubMed:30674671, PubMed:34678144, PubMed:36050480). Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner (PubMed:11103777, PubMed:12646168). Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3 (PubMed:14730312, PubMed:16964285). Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes (NLRP1, NLRP2, NLRP3, NLRP6, AIM2 and probably IFI16) which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:15030775, PubMed:16982856, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMed:21487011, PubMed:23530044, PubMed:24630722, PubMed:25847972, PubMed:29440442, PubMed:30674671, PubMed:33980849, PubMed:34678144, PubMed:34706239). Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death (PubMed:24630722). The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions (PubMed:14499617, PubMed:19234215, PubMed:24630722). Clustered PYCARD nucleates the formation of caspase-1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization (PubMed:24630722). In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1 (PubMed:17349957). In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation (PubMed:16964285). May be involved in RIGI-triggered pro-inflammatory responses and inflammasome activation (PubMed:19915568). In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8 (PubMed:19158675, PubMed:19158676). In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form (PubMed:22732093). Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways (PubMed:12486103, PubMed:16585594). For regulation of NF-kappa-B activating and inhibiting functions have been reported (PubMed:12486103). Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK (PubMed:12486103, PubMed:16585594). Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing (PubMed:16585594). Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590). {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:19915568, ECO:0000269|PubMed:21487011, ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:23530044, ECO:0000269|PubMed:24630722, ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:33980849, ECO:0000269|PubMed:34678144, ECO:0000269|PubMed:34706239, ECO:0000269|PubMed:36050480}.; FUNCTION: [Isoform 2]: May have a regulating effect on the function as inflammasome adapter. {ECO:0000269|PubMed:19759850, ECO:0000269|PubMed:20482797}.; FUNCTION: [Isoform 3]: Seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. {ECO:0000269|PubMed:20482797}. |
| Q9UM73 | ALK | Y1507 | psp | ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) | Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}. |
| Q9UN70 | PCDHGC3 | Y761 | ochoa | Protocadherin gamma-C3 (PCDH-gamma-C3) (Protocadherin-2) (Protocadherin-43) (PC-43) | Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. |
| Q9UPV0 | CEP164 | Y203 | ochoa | Centrosomal protein of 164 kDa (Cep164) | Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1. {ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:23348840}. |
| Q9UQE7 | SMC3 | Y228 | ochoa | Structural maintenance of chromosomes protein 3 (SMC protein 3) (SMC-3) (Basement membrane-associated chondroitin proteoglycan) (Bamacan) (Chondroitin sulfate proteoglycan 6) (Chromosome-associated polypeptide) (hCAP) | Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement. {ECO:0000269|PubMed:11076961, ECO:0000269|PubMed:19907496}. |
| Q9UQE7 | SMC3 | Y669 | ochoa | Structural maintenance of chromosomes protein 3 (SMC protein 3) (SMC-3) (Basement membrane-associated chondroitin proteoglycan) (Bamacan) (Chondroitin sulfate proteoglycan 6) (Chromosome-associated polypeptide) (hCAP) | Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement. {ECO:0000269|PubMed:11076961, ECO:0000269|PubMed:19907496}. |
| Q9Y281 | CFL2 | Y82 | ochoa | Cofilin-2 (Cofilin, muscle isoform) | Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. Its F-actin depolymerization activity is regulated by association with CSPR3 (PubMed:19752190). It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere (By similarity). {ECO:0000250|UniProtKB:P45591, ECO:0000269|PubMed:19752190}. |
| Q9Y281 | CFL2 | Y89 | ochoa | Cofilin-2 (Cofilin, muscle isoform) | Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. Its F-actin depolymerization activity is regulated by association with CSPR3 (PubMed:19752190). It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere (By similarity). {ECO:0000250|UniProtKB:P45591, ECO:0000269|PubMed:19752190}. |
| Q9Y283 | INVS | Y845 | ochoa | Inversin (Inversion of embryo turning homolog) (Nephrocystin-2) | Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:15852005, ECO:0000269|PubMed:18371931}. |
| Q9Y2L6 | FRMD4B | Y674 | ochoa | FERM domain-containing protein 4B (GRP1-binding protein GRSP1) | Member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling. May function as a scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex. Plays a redundant role with FRMD4A in epithelial polarization. {ECO:0000250|UniProtKB:Q920B0}. |
| Q9Y2X7 | GIT1 | Y284 | psp | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y2Z0 | SUGT1 | Y317 | ochoa | Protein SGT1 homolog (Protein 40-6-3) (Sgt1) (Suppressor of G2 allele of SKP1 homolog) | May play a role in ubiquitination and subsequent proteasomal degradation of target proteins. |
| Q9Y4C1 | KDM3A | Y1101 | psp | Lysine-specific demethylase 3A (EC 1.14.11.65) (JmjC domain-containing histone demethylation protein 2A) (Jumonji domain-containing protein 1A) ([histone H3]-dimethyl-L-lysine(9) demethylase 3A) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1. {ECO:0000269|PubMed:16603237, ECO:0000269|PubMed:28262558}. |
| Q9Y4D7 | PLXND1 | Y1673 | ochoa | Plexin-D1 | Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E. Plays an important role in cell-cell signaling, and in regulating the migration of a wide spectrum of cell types. Regulates the migration of thymocytes in the medulla. Regulates endothelial cell migration. Plays an important role in ensuring the specificity of synapse formation. Required for normal development of the heart and vasculature (By similarity). Mediates anti-angiogenic signaling in response to SEMA3E. {ECO:0000250, ECO:0000269|PubMed:20385769}. |
| Q9Y4H2 | IRS2 | Y766 | 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}. |
| Q9Y5X2 | SNX8 | Y95 | psp | Sorting nexin-8 | May be involved in several stages of intracellular trafficking. May play a role in intracellular protein transport from early endosomes to the trans-Golgi network. {ECO:0000269|PubMed:19782049}. |
| Q9Y5X2 | SNX8 | Y126 | psp | Sorting nexin-8 | May be involved in several stages of intracellular trafficking. May play a role in intracellular protein transport from early endosomes to the trans-Golgi network. {ECO:0000269|PubMed:19782049}. |
| Q9Y6D9 | MAD1L1 | Y427 | ochoa | Mitotic spindle assembly checkpoint protein MAD1 (Mitotic arrest deficient 1-like protein 1) (MAD1-like protein 1) (Mitotic checkpoint MAD1 protein homolog) (HsMAD1) (hMAD1) (Tax-binding protein 181) | Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:10049595, PubMed:20133940, PubMed:29162720). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (PubMed:29162720). {ECO:0000269|PubMed:10049595, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:36322655}.; FUNCTION: [Isoform 3]: Sequesters MAD2L1 in the cytoplasm preventing its function as an activator of the mitotic spindle assembly checkpoint (SAC) resulting in SAC impairment and chromosomal instability in hepatocellular carcinomas. {ECO:0000269|PubMed:19010891}. |
| Q9Y6J8 | STYXL1 | Y73 | ochoa | Serine/threonine/tyrosine-interacting-like protein 1 (Dual specificity phosphatase inhibitor MK-STYX) (Dual specificity protein phosphatase 24) (Inactive dual specificity protein phosphatase MK-STYX) (Map kinase phosphatase-like protein MK-STYX) | Catalytically inactive phosphatase (PubMed:20180778, PubMed:23163895). By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules (PubMed:20180778, PubMed:23163895). Does not act by protecting the dephosphorylation of G3BP1 at 'Ser-149' (PubMed:23163895). Inhibits PTPMT1 phosphatase activity (PubMed:24709986). By inhibiting PTPMT1, positively regulates intrinsic apoptosis (PubMed:21262771). May play a role in the formation of neurites during neuronal development (PubMed:29250526). {ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:21262771, ECO:0000269|PubMed:23163895, ECO:0000269|PubMed:24709986, ECO:0000269|PubMed:29250526}. |
| Q9Y6M1 | IGF2BP2 | Y40 | ochoa | Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2 mRNA-binding protein 2) (IMP-2) (Hepatocellular carcinoma autoantigen p62) (IGF-II mRNA-binding protein 2) (VICKZ family member 2) | RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (PubMed:29476152). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs (PubMed:9891060). Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (PubMed:29476152). {ECO:0000250, ECO:0000269|PubMed:23640942, ECO:0000269|PubMed:29476152, ECO:0000269|PubMed:9891060}. |
| Q9Y6N7 | ROBO1 | Y1476 | ochoa | Roundabout homolog 1 (Deleted in U twenty twenty) (H-Robo-1) | Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10102268, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). May be required for lung development (By similarity). {ECO:0000250|UniProtKB:O89026, ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:24560577, ECO:0000269|PubMed:26529257, ECO:0000305}. |
| Q9Y6X2 | PIAS3 | Y430 | ochoa | E3 SUMO-protein ligase PIAS3 (EC 2.3.2.-) (E3 SUMO-protein transferase PIAS3) (Protein inhibitor of activated STAT protein 3) | Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678, PubMed:9388184). Sumoylates CCAR2 which promotes its interaction with SIRT1 (PubMed:25406032). Diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus (PubMed:24651376). {ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:25406032, ECO:0000269|PubMed:9388184}. |
| P50454 | SERPINH1 | Y135 | Sugiyama | Serpin H1 (47 kDa heat shock protein) (Arsenic-transactivated protein 3) (AsTP3) (Cell proliferation-inducing gene 14 protein) (Collagen-binding protein) (Colligin) (Rheumatoid arthritis-related antigen RA-A47) | Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen. |
| A1X283 | SH3PXD2B | Y855 | Sugiyama | SH3 and PX domain-containing protein 2B (Adapter protein HOFI) (Factor for adipocyte differentiation 49) (Tyrosine kinase substrate with four SH3 domains) | Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. Plays a role in mitotic clonal expansion during the immediate early stage of adipocyte differentiation (By similarity). {ECO:0000250, ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}. |
| O15146 | MUSK | Y570 | Sugiyama | Muscle, skeletal receptor tyrosine-protein kinase (EC 2.7.10.1) (Muscle-specific tyrosine-protein kinase receptor) (MuSK) (Muscle-specific kinase receptor) | Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:25537362}. |
| O15146 | MUSK | Y751 | Sugiyama | Muscle, skeletal receptor tyrosine-protein kinase (EC 2.7.10.1) (Muscle-specific tyrosine-protein kinase receptor) (MuSK) (Muscle-specific kinase receptor) | Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:25537362}. |
| O43390 | HNRNPR | Y136 | Sugiyama | Heterogeneous nuclear ribonucleoprotein R (hnRNP R) | Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus. |
| O60506 | SYNCRIP | Y133 | Sugiyama | Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) (Glycine- and tyrosine-rich RNA-binding protein) (GRY-RBP) (NS1-associated protein 1) (Synaptotagmin-binding, cytoplasmic RNA-interacting protein) | Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; seems not to be essential for GAIT complex function. {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:11134005, ECO:0000269|PubMed:11352648, ECO:0000269|PubMed:11574476, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:23071094}. |
| O75817 | POP7 | Y20 | Sugiyama | Ribonuclease P protein subunit p20 (RNaseP protein p20) (Ribonucleases P/MRP protein subunit POP7 homolog) (hPOP7) | Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:30454648, PubMed:9630247). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465). {ECO:0000269|PubMed:28115465, ECO:0000269|PubMed:30454648, ECO:0000269|PubMed:9630247}. |
| P00966 | ASS1 | Y359 | Sugiyama | Argininosuccinate synthase (EC 6.3.4.5) (Citrulline--aspartate ligase) | One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues. {ECO:0000305|PubMed:18473344, ECO:0000305|PubMed:27287393, ECO:0000305|PubMed:8792870}. |
| P13796 | LCP1 | Y462 | Sugiyama | Plastin-2 (L-plastin) (LC64P) (Lymphocyte cytosolic protein 1) (LCP-1) | Actin-binding protein (PubMed:16636079, PubMed:17294403, PubMed:28493397). Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28 (PubMed:17294403). Modulates the cell surface expression of IL2RA/CD25 and CD69 (PubMed:17294403). {ECO:0000269|PubMed:16636079, ECO:0000269|PubMed:17294403, ECO:0000269|PubMed:28493397}. |
| P13797 | PLS3 | Y465 | Sugiyama | Plastin-3 (T-fimbrin) (T-plastin) | Actin-bundling protein. |
| P14625 | HSP90B1 | Y652 | Sugiyama | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P22314 | UBA1 | Y873 | Sugiyama | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
| P30101 | PDIA3 | Y467 | Sugiyama | Protein disulfide-isomerase A3 (EC 5.3.4.1) (58 kDa glucose-regulated protein) (58 kDa microsomal protein) (p58) (Disulfide isomerase ER-60) (Endoplasmic reticulum resident protein 57) (ER protein 57) (ERp57) (Endoplasmic reticulum resident protein 60) (ER protein 60) (ERp60) | Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone (PubMed:11825568, PubMed:16193070, PubMed:27897272, PubMed:36104323, PubMed:7487104). Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity (PubMed:35948544, PubMed:36104323). {ECO:0000269|PubMed:11825568, ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:27897272, ECO:0000269|PubMed:35948544, ECO:0000269|PubMed:36104323, ECO:0000269|PubMed:7487104}. |
| P33316 | DUT | Y167 | Sugiyama | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase) | Catalyzes the cleavage of 2'-deoxyuridine 5'-triphosphate (dUTP) into 2'-deoxyuridine 5'-monophosphate (dUMP) and inorganic pyrophosphate and through its action efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo thymidylate biosynthesis (PubMed:17880943, PubMed:8631816, PubMed:8805593). Inhibits peroxisome proliferator-activated receptor (PPAR) activity by binding of its N-terminal to PPAR, preventing the latter's dimerization with retinoid X receptor (By similarity). Essential for embryonic development (By similarity). {ECO:0000250|UniProtKB:P70583, ECO:0000250|UniProtKB:Q9CQ43, ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593}. |
| P43034 | PAFAH1B1 | Y24 | Sugiyama | Platelet-activating factor acetylhydrolase IB subunit beta (Lissencephaly-1 protein) (LIS-1) (PAF acetylhydrolase 45 kDa subunit) (PAF-AH 45 kDa subunit) (PAF-AH alpha) (PAFAH alpha) | Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (PubMed:22956769). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (By similarity). {ECO:0000250|UniProtKB:P43033, ECO:0000250|UniProtKB:P63005, ECO:0000269|PubMed:15173193, ECO:0000269|PubMed:22956769}. |
| P43490 | NAMPT | Y188 | Sugiyama | Nicotinamide phosphoribosyltransferase (NAmPRTase) (Nampt) (EC 2.4.2.12) (Pre-B-cell colony-enhancing factor 1) (Pre-B cell-enhancing factor) (Visfatin) | Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity). {ECO:0000250|UniProtKB:Q99KQ4, ECO:0000269|PubMed:24130902}. |
| P52948 | NUP98 | Y741 | Sugiyama | Nuclear pore complex protein Nup98-Nup96 (EC 3.4.21.-) [Cleaved into: Nuclear pore complex protein Nup98 (98 kDa nucleoporin) (Nucleoporin Nup98) (Nup98); Nuclear pore complex protein Nup96 (96 kDa nucleoporin) (Nucleoporin Nup96) (Nup96)] | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC (PubMed:33097660). May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:33097660}.; FUNCTION: (Microbial infection) Interacts with HIV-1 capsid protein P24 and nucleocapsid protein P7 and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change Asn-74-Asp is reduced (in vitro) (PubMed:23523133). {ECO:0000269|PubMed:23523133}. |
| P52948 | NUP98 | Y848 | Sugiyama | Nuclear pore complex protein Nup98-Nup96 (EC 3.4.21.-) [Cleaved into: Nuclear pore complex protein Nup98 (98 kDa nucleoporin) (Nucleoporin Nup98) (Nup98); Nuclear pore complex protein Nup96 (96 kDa nucleoporin) (Nucleoporin Nup96) (Nup96)] | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC (PubMed:33097660). May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:33097660}.; FUNCTION: (Microbial infection) Interacts with HIV-1 capsid protein P24 and nucleocapsid protein P7 and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change Asn-74-Asp is reduced (in vitro) (PubMed:23523133). {ECO:0000269|PubMed:23523133}. |
| P53396 | ACLY | Y652 | Sugiyama | ATP-citrate synthase (EC 2.3.3.8) (ATP-citrate (pro-S-)-lyase) (ACL) (Citrate cleavage enzyme) | Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism. {ECO:0000269|PubMed:10653665, ECO:0000269|PubMed:1371749, ECO:0000269|PubMed:19286649, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:39881208, ECO:0000269|PubMed:9116495}. |
| P54577 | YARS1 | Y204 | Sugiyama | Tyrosine--tRNA ligase, cytoplasmic (EC 6.1.1.1) (Tyrosyl-tRNA synthetase) (TyrRS) [Cleaved into: Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed] | Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949). Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949). {ECO:0000269|PubMed:25533949, ECO:0000305|PubMed:16429158, ECO:0000305|PubMed:9162081}. |
| P61353 | RPL27 | Y85 | Sugiyama | Large ribosomal subunit protein eL27 (60S ribosomal protein L27) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs (PubMed:25424902). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25424902, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| Q08J23 | NSUN2 | Y52 | Sugiyama | RNA cytosine C(5)-methyltransferase NSUN2 (EC 2.1.1.-) (Myc-induced SUN domain-containing protein) (Misu) (NOL1/NOP2/Sun domain family member 2) (Substrate of AIM1/Aurora kinase B) (mRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-) (tRNA cytosine C(5)-methyltransferase) (EC 2.1.1.-, EC 2.1.1.203) (tRNA methyltransferase 4 homolog) (hTrm4) | RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847). {ECO:0000250|UniProtKB:Q1HFZ0, ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:22995836, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31199786, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969, ECO:0000269|PubMed:34556860}. |
| Q13601 | KRR1 | Y287 | Sugiyama | KRR1 small subunit processome component homolog (HIV-1 Rev-binding protein 2) (KRR-R motif-containing protein 1) (Rev-interacting protein 1) (Rip-1) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. {ECO:0000269|PubMed:34516797}. |
| Q14974 | KPNB1 | Y529 | Sugiyama | Importin subunit beta-1 (Importin-90) (Karyopherin subunit beta-1) (Nuclear factor p97) (Pore targeting complex 97 kDa subunit) (PTAC97) | Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). Acting autonomously, serves itself as NLS receptor (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:24699649, PubMed:7615630, PubMed:9687515). Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607, PubMed:9687515). In association with IPO7, mediates the nuclear import of H1 histone (PubMed:10228156). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (By similarity). Imports MRTFA, SNAI1 and PRKCI into the nucleus (PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649). {ECO:0000250|UniProtKB:P70168, ECO:0000269|PubMed:10228156, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:19386897, ECO:0000269|PubMed:20818336, ECO:0000269|PubMed:24699649, ECO:0000269|PubMed:7615630, ECO:0000269|PubMed:9687515}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000269|PubMed:16704975, ECO:0000269|PubMed:9405152, ECO:0000269|PubMed:9891055}. |
| Q16763 | UBE2S | Y141 | Sugiyama | Ubiquitin-conjugating enzyme E2 S (EC 2.3.2.23) (E2 ubiquitin-conjugating enzyme S) (E2-EPF) (Ubiquitin carrier protein S) (Ubiquitin-conjugating enzyme E2-24 kDa) (Ubiquitin-conjugating enzyme E2-EPF5) (Ubiquitin-protein ligase S) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:19820702, PubMed:19822757, PubMed:22496338, PubMed:27259151). Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis (PubMed:19820702, PubMed:19822757, PubMed:27259151, PubMed:27910872). Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit (PubMed:19820702, PubMed:19822757, PubMed:27259151). Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as an E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A (PubMed:16819549). In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination (PubMed:20061386, PubMed:20622874). {ECO:0000269|PubMed:16819549, ECO:0000269|PubMed:19820702, ECO:0000269|PubMed:19822757, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22496338, ECO:0000269|PubMed:27259151, ECO:0000269|PubMed:27910872}. |
| Q96HE7 | ERO1A | Y73 | Sugiyama | ERO1-like protein alpha (ERO1-L) (ERO1-L-alpha) (EC 1.8.4.-) (Endoplasmic oxidoreductin-1-like protein) (Endoplasmic reticulum oxidoreductase alpha) (Oxidoreductin-1-L-alpha) | Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. Required for the proper folding of immunoglobulins (PubMed:29858230). Plays an important role in ER stress-induced, CHOP-dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1. Involved in the release of the unfolded cholera toxin from reduced P4HB/PDI in case of infection by V.cholerae, thereby playing a role in retrotranslocation of the toxin. {ECO:0000269|PubMed:10671517, ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:11707400, ECO:0000269|PubMed:12403808, ECO:0000269|PubMed:18833192, ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:23027870, ECO:0000269|PubMed:29858230}. |
| Q99543 | DNAJC2 | Y274 | Sugiyama | DnaJ homolog subfamily C member 2 (M-phase phosphoprotein 11) (Zuotin-related factor 1) [Cleaved into: DnaJ homolog subfamily C member 2, N-terminally processed] | Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation. {ECO:0000269|PubMed:15802566, ECO:0000269|PubMed:16002468, ECO:0000269|PubMed:21179169}. |
| Q9BS40 | LXN | Y20 | Sugiyama | Latexin (Endogenous carboxypeptidase inhibitor) (ECI) (Protein MUM) (Tissue carboxypeptidase inhibitor) (TCI) | Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4. May play a role in inflammation. {ECO:0000269|PubMed:15738388}. |
| P29322 | EPHA8 | Y756 | Sugiyama | Ephrin type-A receptor 8 (EC 2.7.10.1) (EPH- and ELK-related kinase) (EPH-like kinase 3) (EK3) (hEK3) (Tyrosine-protein kinase receptor EEK) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity). {ECO:0000250}. |
| O43781 | DYRK3 | Y32 | Sugiyama | Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC 2.7.12.1) (Regulatory erythroid kinase) (REDK) | Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:29634919, PubMed:9748265). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}. |
| O15230 | LAMA5 | Y823 | Sugiyama | Laminin subunit alpha-5 (Laminin-10 subunit alpha) (Laminin-11 subunit alpha) (Laminin-15 subunit alpha) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Plays a role in the regulation of skeletogenesis, through a mechanism that involves integrin-mediated signaling and PTK2B/PYK2 (PubMed:33242826). {ECO:0000269|PubMed:33242826}. |
| O75083 | WDR1 | Y98 | Sugiyama | WD repeat-containing protein 1 (Actin-interacting protein 1) (AIP1) (NORI-1) | Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (PubMed:15629458, PubMed:27557945, PubMed:29751004). Enhances cofilin-mediated actin severing (By similarity). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (PubMed:18494608). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance (By similarity). Involved in megakaryocyte maturation and platelet shedding. Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (By similarity). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (PubMed:25792565). {ECO:0000250|UniProtKB:O88342, ECO:0000250|UniProtKB:Q9W7F2, ECO:0000269|PubMed:15629458, ECO:0000269|PubMed:18494608, ECO:0000269|PubMed:25792565, ECO:0000269|PubMed:27557945, ECO:0000269|PubMed:29751004}. |
| P02786 | TFRC | Y152 | Sugiyama | Transferrin receptor protein 1 (TR) (TfR) (TfR1) (Trfr) (T9) (p90) (CD antigen CD71) [Cleaved into: Transferrin receptor protein 1, serum form (sTfR)] | Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity). {ECO:0000250|UniProtKB:Q62351, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus. {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.; FUNCTION: (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762, ECO:0000269|PubMed:36779763}.; FUNCTION: (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762}. |
| Q9NVR5 | DNAAF2 | Y697 | Sugiyama | Protein kintoun (Dynein assembly factor 2, axonemal) | Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment. {ECO:0000255|HAMAP-Rule:MF_03069}. |
| Q5BKZ1 | ZNF326 | Y93 | Sugiyama | DBIRD complex subunit ZNF326 (Zinc finger protein 326) (Zinc finger protein interacting with mRNPs and DBC1) | Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions. May play a role in neuronal differentiation and is able to bind DNA and activate expression in vitro. {ECO:0000269|PubMed:22446626}. |
| Q86W56 | PARG | Y832 | Sugiyama | Poly(ADP-ribose) glycohydrolase (EC 3.2.1.143) | Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose) (PubMed:15450800, PubMed:21892188, PubMed:23102699, PubMed:23474714, PubMed:33186521, PubMed:34019811, PubMed:34321462). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers (PubMed:23102699, PubMed:23481255). It is however unable to cleave the ester bond between the terminal ADP-ribose and ADP-ribosylated residues, leaving proteins that are mono-ADP-ribosylated (PubMed:21892188, PubMed:23474714, PubMed:33186521). Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG (PubMed:23102699, PubMed:34019811). Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress (PubMed:24906880). Responsible for the prevalence of mono-ADP-ribosylated proteins in cells, thanks to its ability to degrade poly(ADP-ribose) without cleaving the terminal protein-ribose bond (PubMed:33186521). Required for retinoid acid-dependent gene transactivation, probably by removing poly(ADP-ribose) from histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters (PubMed:23102699). Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000269|PubMed:15450800, ECO:0000269|PubMed:21892188, ECO:0000269|PubMed:23102699, ECO:0000269|PubMed:23474714, ECO:0000269|PubMed:23481255, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34321462}. |
| P00519 | ABL1 | Y93 | Sugiyama | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P23396 | RPS3 | Y34 | Sugiyama | Small ribosomal subunit protein uS3 (40S ribosomal protein S3) (EC 4.2.99.18) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:8706699). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:8706699). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (PubMed:15707971). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Has also been shown to bind with similar affinity to intact and damaged DNA (PubMed:18610840). Stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571). Enhances the uracil excision activity of UNG1 (PubMed:18973764). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (PubMed:18045535). Represses its own translation by binding to its cognate mRNA (PubMed:20217897). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408). {ECO:0000269|PubMed:14706345, ECO:0000269|PubMed:14988002, ECO:0000269|PubMed:15518571, ECO:0000269|PubMed:15707971, ECO:0000269|PubMed:17049931, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:18610840, ECO:0000269|PubMed:18973764, ECO:0000269|PubMed:19656744, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:22510408, ECO:0000269|PubMed:23131551, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:23911537, ECO:0000269|PubMed:7775413, ECO:0000269|PubMed:8706699}. |
| P31947 | SFN | Y213 | Sugiyama | 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}. |
| P43490 | NAMPT | Y195 | Sugiyama | Nicotinamide phosphoribosyltransferase (NAmPRTase) (Nampt) (EC 2.4.2.12) (Pre-B-cell colony-enhancing factor 1) (Pre-B cell-enhancing factor) (Visfatin) | Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity). {ECO:0000250|UniProtKB:Q99KQ4, ECO:0000269|PubMed:24130902}. |
| P48163 | ME1 | Y208 | Sugiyama | NADP-dependent malic enzyme (NADP-ME) (EC 1.1.1.40) (Malic enzyme 1) | Catalyzes the oxidative decarboxylation of (S)-malate in the presence of NADP(+) and divalent metal ions, and decarboxylation of oxaloacetate. {ECO:0000269|PubMed:7622060, ECO:0000269|PubMed:7757881, ECO:0000269|PubMed:8187880, ECO:0000269|PubMed:8804575}. |
| P53621 | COPA | Y391 | Sugiyama | Coatomer subunit alpha (Alpha-coat protein) (Alpha-COP) (HEP-COP) (HEPCOP) [Cleaved into: Xenin (Xenopsin-related peptide); Proxenin] | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}.; FUNCTION: Xenin stimulates exocrine pancreatic secretion. It inhibits pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic secretion and to affect small and large intestinal motility. In the gut, xenin interacts with the neurotensin receptor. |
| P53675 | CLTCL1 | Y921 | Sugiyama | Clathrin heavy chain 2 (Clathrin heavy chain on chromosome 22) (CLH-22) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network (By similarity). {ECO:0000250}. |
| P55072 | VCP | Y203 | Sugiyama | Transitional endoplasmic reticulum ATPase (TER ATPase) (EC 3.6.4.6) (15S Mg(2+)-ATPase p97 subunit) (Valosin-containing protein) (VCP) | Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Involved in clearance process by mediating G3BP1 extraction from stress granules (PubMed:29804830, PubMed:34739333). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042605, PubMed:23042607). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (PubMed:35013556). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:P23787, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:35013556}. |
| P63010 | AP2B1 | Y524 | Sugiyama | AP-2 complex subunit beta (AP105B) (Adaptor protein complex AP-2 subunit beta) (Adaptor-related protein complex 2 subunit beta) (Beta-2-adaptin) (Beta-adaptin) (Clathrin assembly protein complex 2 beta large chain) (Plasma membrane adaptor HA2/AP2 adaptin beta subunit) | Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly. {ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:14985334, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:19033387, ECO:0000269|PubMed:23676497}. |
| Q00610 | CLTC | Y921 | Sugiyama | Clathrin heavy chain 1 (Clathrin heavy chain on chromosome 17) (CLH-17) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating (By similarity). {ECO:0000250|UniProtKB:P49951, ECO:0000269|PubMed:15858577, ECO:0000269|PubMed:16968737, ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| Q10567 | AP1B1 | Y524 | Sugiyama | AP-1 complex subunit beta-1 (Adaptor protein complex AP-1 subunit beta-1) (Adaptor-related protein complex 1 subunit beta-1) (Beta-1-adaptin) (Beta-adaptin 1) (Clathrin assembly protein complex 1 beta large chain) (Golgi adaptor HA1/AP1 adaptin beta subunit) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes (PubMed:31630791). The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. {ECO:0000269|PubMed:31630791}. |
| Q13242 | SRSF9 | Y35 | Sugiyama | Serine/arginine-rich splicing factor 9 (Pre-mRNA-splicing factor SRp30C) (Splicing factor, arginine/serine-rich 9) | Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:10196175, ECO:0000269|PubMed:11875052, ECO:0000269|PubMed:12024014, ECO:0000269|PubMed:12604611, ECO:0000269|PubMed:15009090, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:15695522, ECO:0000269|PubMed:7556075}. |
| Q6P1L8 | MRPL14 | Y51 | Sugiyama | Large ribosomal subunit protein uL14m (39S ribosomal protein L14, mitochondrial) (L14mt) (MRP-L14) (39S ribosomal protein L32, mitochondrial) (L32mt) (MRP-L32) | Forms part of 2 intersubunit bridges in the assembled ribosome. Upon binding to MALSU1 intersubunit bridge formation is blocked, preventing ribosome formation and repressing translation (Probable). {ECO:0000305|PubMed:22829778}. |
| Q6P2Q9 | PRPF8 | Y871 | Sugiyama | Pre-mRNA-processing-splicing factor 8 (220 kDa U5 snRNP-specific protein) (PRP8 homolog) (Splicing factor Prp8) (p220) | Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome (PubMed:10411133, PubMed:11971955, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154, PubMed:30728453). Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome. Functions as a scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site. {ECO:0000269|PubMed:10411133, ECO:0000269|PubMed:11971955, ECO:0000269|PubMed:20595234, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000303|PubMed:15840809}. |
| Q709C8 | VPS13C | Y310 | Sugiyama | Intermembrane lipid transfer protein VPS13C (Vacuolar protein sorting-associated protein 13C) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential (PubMed:26942284). Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization (PubMed:26942284). {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:26942284}. |
| Q93009 | USP7 | Y243 | SIGNOR | Ubiquitin carboxyl-terminal hydrolase 7 (EC 3.4.19.12) (Deubiquitinating enzyme 7) (Herpesvirus-associated ubiquitin-specific protease) (Ubiquitin thioesterase 7) (Ubiquitin-specific-processing protease 7) | Hydrolase that deubiquitinates target proteins such as ARMC5, FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:25865756, PubMed:26678539, PubMed:28655758, PubMed:33544460, PubMed:35216969). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872, PubMed:26786098). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:21745816, PubMed:22411829). Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins (PubMed:27123980). Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells (PubMed:21258371). Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis (PubMed:28655758). Involved in the regulation of WASH-dependent actin polymerization at the surface of endosomes and the regulation of endosomal protein recycling (PubMed:26365382). It maintains optimal WASH complex activity and precise F-actin levels via deubiquitination of TRIM27 and WASHC1 (PubMed:26365382). Mediates the deubiquitination of phosphorylated DEPTOR, promoting its stability and leading to decreased mTORC1 signaling (PubMed:35216969). {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:25865756, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:26365382, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:26786098, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28655758, ECO:0000269|PubMed:33544460, ECO:0000269|PubMed:35216969}.; FUNCTION: (Microbial infection) Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. {ECO:0000269|PubMed:14506283, ECO:0000269|PubMed:16160161, ECO:0000269|PubMed:18590780}.; FUNCTION: (Microbial infection) Upon infection with Epstein-Barr virus, the interaction with viral EBNA1 increases the association of USP7 with PML proteins, which is required for the polyubiquitylation and degradation of PML. {ECO:0000269|PubMed:20719947, ECO:0000269|PubMed:24216761}. |
| Q9Y265 | RUVBL1 | Y220 | Sugiyama | RuvB-like 1 (EC 3.6.4.12) (49 kDa TATA box-binding protein-interacting protein) (49 kDa TBP-interacting protein) (54 kDa erythrocyte cytosolic protein) (ECP-54) (INO80 complex subunit H) (Nuclear matrix protein 238) (NMP 238) (Pontin 52) (TIP49a) (TIP60-associated protein 54-alpha) (TAP54-alpha) | Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:17157868, PubMed:33205750). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). Essential for cell proliferation (PubMed:14506706). May be able to bind plasminogen at cell surface and enhance plasminogen activation (PubMed:11027681). {ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:11027681, ECO:0000269|PubMed:14506706, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:33205750}. |
| O00488 | ZNF593 | Y97 | Sugiyama | Zinc finger protein 593 (Zinc finger protein T86) | Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome (PubMed:32669547). Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity (PubMed:9115366). {ECO:0000269|PubMed:9115366, ECO:0000305|PubMed:32669547}. |
| P39687 | ANP32A | Y144 | Sugiyama | Acidic leucine-rich nuclear phosphoprotein 32 family member A (Acidic nuclear phosphoprotein pp32) (pp32) (Leucine-rich acidic nuclear protein) (LANP) (Mapmodulin) (Potent heat-stable protein phosphatase 2A inhibitor I1PP2A) (Putative HLA-DR-associated protein I) (PHAPI) | Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription (PubMed:10400610, PubMed:11360199, PubMed:16341127, PubMed:18439902). Promotes apoptosis by favouring the activation of caspase-9/CASP9 and allowing apoptosome formation (PubMed:18439902). In addition, plays a role in the modulation of histone acetylation and transcription as part of the INHAT (inhibitor of histone acetyltransferases) complex. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking (PubMed:11830591). Preferentially binds to unmodified histone H3 and sterically inhibiting its acetylation and phosphorylation leading to cell growth inhibition (PubMed:16341127). Participates in other biochemical processes such as regulation of mRNA nuclear-to-cytoplasmic translocation and stability by its association with ELAVL1 (Hu-antigen R) (PubMed:18180367). Plays a role in E4F1-mediated transcriptional repression as well as inhibition of protein phosphatase 2A (PubMed:15642345, PubMed:17557114). {ECO:0000269|PubMed:10400610, ECO:0000269|PubMed:11360199, ECO:0000269|PubMed:11830591, ECO:0000269|PubMed:15642345, ECO:0000269|PubMed:16341127, ECO:0000269|PubMed:17557114, ECO:0000269|PubMed:18180367, ECO:0000269|PubMed:18439902}.; FUNCTION: (Microbial infection) Plays an essential role in influenza A, B and C viral genome replication (PubMed:30666459, PubMed:32694517, PubMed:33045004, PubMed:33208942). Mechanistically, mediates the assembly of the viral replicase asymmetric dimers composed of PB1, PB2 and PA via its N-terminal region (PubMed:33208942). Also plays an essential role in foamy virus mRNA export from the nucleus (PubMed:21159877). {ECO:0000269|PubMed:21159877, ECO:0000269|PubMed:30666459, ECO:0000269|PubMed:32694517, ECO:0000269|PubMed:33045004, ECO:0000269|PubMed:33208942}. |
| Q9Y4L1 | HYOU1 | Y759 | Sugiyama | Hypoxia up-regulated protein 1 (150 kDa oxygen-regulated protein) (ORP-150) (170 kDa glucose-regulated protein) (GRP-170) (Heat shock protein family H member 4) | Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. Promotes HSPA5/BiP-mediated ATP nucleotide exchange and thereby activates the unfolded protein response (UPR) pathway in the presence of endoplasmic reticulum stress (By similarity). May play a role as a molecular chaperone and participate in protein folding. {ECO:0000250|UniProtKB:Q9JKR6, ECO:0000269|PubMed:10037731}. |
| Q9Y5Q8 | GTF3C5 | Y393 | Sugiyama | General transcription factor 3C polypeptide 5 (TF3C-epsilon) (Transcription factor IIIC 63 kDa subunit) (TFIIIC 63 kDa subunit) (TFIIIC63) (Transcription factor IIIC subunit epsilon) | Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters. |
| O43707 | ACTN4 | Y799 | Sugiyama | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| P08195 | SLC3A2 | Y404 | Sugiyama | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| P13674 | P4HA1 | Y250 | Sugiyama | Prolyl 4-hydroxylase subunit alpha-1 (4-PH alpha-1) (EC 1.14.11.2) (Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1) | Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. {ECO:0000269|PubMed:9211872}. |
| P18124 | RPL7 | Y195 | Sugiyama | Large ribosomal subunit protein uL30 (60S ribosomal protein L7) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). Binds to G-rich structures in 28S rRNA and in mRNAs (PubMed:12962325). Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs (PubMed:12962325). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P23588 | EIF4B | Y105 | Sugiyama | Eukaryotic translation initiation factor 4B (eIF-4B) | Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F. |
| Q9Y3F4 | STRAP | Y252 | Sugiyama | Serine-threonine kinase receptor-associated protein (MAP activator with WD repeats) (UNR-interacting protein) (WD-40 repeat protein PT-WD) | The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein. {ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:18984161}. |
| O75718 | CRTAP | Y372 | Sugiyama | Cartilage-associated protein | Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues. {ECO:0000269|PubMed:17055431}. |
| O95295 | SNAPIN | Y81 | Sugiyama | SNARE-associated protein Snapin (Biogenesis of lysosome-related organelles complex 1 subunit 7) (BLOC-1 subunit 7) (Synaptosomal-associated protein 25-binding protein) (SNAP-associated protein) | Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling. May modulate a step between vesicle priming, fusion and calcium-dependent neurotransmitter release through its ability to potentiate the interaction of synaptotagmin with the SNAREs and the plasma-membrane-associated protein SNAP25. Its phosphorylation state influences exocytotic protein interactions and may regulate synaptic vesicle exocytosis. May also have a role in the mechanisms of SNARE-mediated membrane fusion in non-neuronal cells (PubMed:17182842, PubMed:18167355). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (PubMed:25898167). {ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:18167355, ECO:0000269|PubMed:25898167}. |
| P23588 | EIF4B | Y141 | Sugiyama | Eukaryotic translation initiation factor 4B (eIF-4B) | Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F. |
| P55072 | VCP | Y644 | Sugiyama | Transitional endoplasmic reticulum ATPase (TER ATPase) (EC 3.6.4.6) (15S Mg(2+)-ATPase p97 subunit) (Valosin-containing protein) (VCP) | Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139). Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). Involved in clearance process by mediating G3BP1 extraction from stress granules (PubMed:29804830, PubMed:34739333). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites (PubMed:22020440, PubMed:22120668). Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage (PubMed:23042605, PubMed:23042607). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (PubMed:35013556). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:P23787, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26265139, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:35013556}. |
| Q99832 | CCT7 | Y438 | Sugiyama | T-complex protein 1 subunit eta (TCP-1-eta) (EC 3.6.1.-) (CCT-eta) (Chaperonin containing T-complex polypeptide 1 subunit 7) (HIV-1 Nef-interacting protein) [Cleaved into: T-complex protein 1 subunit eta, N-terminally processed] | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| O14980 | XPO1 | Y469 | Sugiyama | Exportin-1 (Exp1) (Chromosome region maintenance 1 protein homolog) | Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. {ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:20921223, ECO:0000269|PubMed:9311922, ECO:0000269|PubMed:9323133}.; FUNCTION: (Microbial infection) Mediates the export of unspliced or incompletely spliced RNAs out of the nucleus from different viruses including HIV-1, HTLV-1 and influenza A. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization. {ECO:0000269|PubMed:14612415, ECO:0000269|PubMed:9837918}. |
| O75446 | SAP30 | Y202 | Sugiyama | Histone deacetylase complex subunit SAP30 (30 kDa Sin3-associated polypeptide) (Sin3 corepressor complex subunit SAP30) (Sin3-associated polypeptide p30) | Involved in the functional recruitment of the Sin3-histone deacetylase complex (HDAC) to a specific subset of N-CoR corepressor complexes. Capable of transcription repression by N-CoR. Active in deacetylating core histone octamers (when in a complex) but inactive in deacetylating nucleosomal histones. {ECO:0000250|UniProtKB:O88574, ECO:0000269|PubMed:9651585}.; FUNCTION: (Microbial infection) Involved in transcriptional repression of HHV-1 genes TK and gC. {ECO:0000269|PubMed:21221920}. |
| P08243 | ASNS | Y140 | Sugiyama | Asparagine synthetase [glutamine-hydrolyzing] (EC 6.3.5.4) (Cell cycle control protein TS11) (Glutamine-dependent asparagine synthetase) | None |
| P10586 | PTPRF | Y1861 | EPSD | Receptor-type tyrosine-protein phosphatase F (EC 3.1.3.48) (Leukocyte common antigen related) (LAR) | Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity.; FUNCTION: The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. |
| P14927 | UQCRB | Y56 | Sugiyama | Cytochrome b-c1 complex subunit 7 (Complex III subunit 7) (Complex III subunit VII) (QP-C) (Ubiquinol-cytochrome c reductase complex 14 kDa protein) | Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. {ECO:0000250|UniProtKB:P00128}. |
| P31751 | AKT2 | Y327 | Sugiyama | RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-2) (Protein kinase B beta) (PKB beta) (RAC protein kinase beta) (RAC-PK-beta) | Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (PubMed:21432781, PubMed:21620960). In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth (PubMed:31204173). Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion (By similarity). Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation (PubMed:23444369). {ECO:0000250|UniProtKB:Q60823, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:31204173, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.; FUNCTION: Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity). {ECO:0000250|UniProtKB:Q60823}. |
| P36776 | LONP1 | Y492 | Sugiyama | Lon protease homolog, mitochondrial (EC 3.4.21.53) (LONHs) (Lon protease-like protein) (LONP) (Mitochondrial ATP-dependent protease Lon) (Serine protease 15) | ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix (PubMed:12198491, PubMed:15870080, PubMed:17579211, PubMed:37327776, PubMed:8248235). Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, DELE1, helicase Twinkle (TWNK) and the large ribosomal subunit protein MRPL32/bL32m (PubMed:17579211, PubMed:28377575, PubMed:37327776). MRPL32/bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575). May also have a chaperone function in the assembly of inner membrane protein complexes (By similarity). Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome (PubMed:17420247). Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner (PubMed:17420247). May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters (PubMed:14739292, PubMed:17420247). {ECO:0000255|HAMAP-Rule:MF_03120, ECO:0000269|PubMed:12198491, ECO:0000269|PubMed:14739292, ECO:0000269|PubMed:15870080, ECO:0000269|PubMed:17420247, ECO:0000269|PubMed:17579211, ECO:0000269|PubMed:28377575, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:8248235}. |
| Q5VUA4 | ZNF318 | Y1573 | Sugiyama | Zinc finger protein 318 (Endocrine regulatory protein) | [Isoform 2]: Acts as a transcriptional corepressor for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}.; FUNCTION: [Isoform 1]: Acts as a transcriptional coactivator for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}. |
| Q99584 | S100A13 | Y76 | Sugiyama | Protein S100-A13 (S100 calcium-binding protein A13) | Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine (By similarity). {ECO:0000250|UniProtKB:P97352, ECO:0000269|PubMed:12746488, ECO:0000269|PubMed:20863990}. |
| Q9UMS4 | PRPF19 | Y108 | Sugiyama | Pre-mRNA-processing factor 19 (EC 2.3.2.27) (Nuclear matrix protein 200) (PRP19/PSO4 homolog) (hPso4) (RING-type E3 ubiquitin transferase PRP19) (Senescence evasion factor) | Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome (PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:30705154). Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex (PubMed:20595234). Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries (PubMed:21536736). The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair (PubMed:17981804). Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response (PubMed:24332808). May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA (PubMed:18263876). As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process (PubMed:16223718). In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:11435423). May play a role in the biogenesis of lipid droplets (By similarity). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity). {ECO:0000250|UniProtKB:Q99KP6, ECO:0000250|UniProtKB:Q9JMJ4, ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:12960389, ECO:0000269|PubMed:15660529, ECO:0000269|PubMed:16223718, ECO:0000269|PubMed:16332694, ECO:0000269|PubMed:16388800, ECO:0000269|PubMed:17349974, ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:21536736, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30705154, ECO:0000303|PubMed:17981804, ECO:0000303|PubMed:20595234}. |
| Q9Y243 | AKT3 | Y323 | Sugiyama | RAC-gamma serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-3) (Protein kinase B gamma) (PKB gamma) (RAC-PK-gamma) (STK-2) | AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. {ECO:0000269|PubMed:18524868, ECO:0000269|PubMed:21191416}. |
| O00571 | DDX3X | Y343 | Sugiyama | ATP-dependent RNA helicase DDX3X (EC 3.6.4.13) (CAP-Rf) (DEAD box protein 3, X-chromosomal) (DEAD box, X isoform) (DBX) (Helicase-like protein 2) (HLP2) | Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:17667941, PubMed:18628297, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150). This function depends on helicase activity (PubMed:20837705, PubMed:22872150). Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705). Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150). Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517). Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705). May activate TP53 translation (PubMed:28842590). Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517). Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941). Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:20127681, PubMed:21170385, PubMed:31575075). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385, PubMed:33674311). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:19913487, PubMed:21170385, PubMed:27980081). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265). Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167). Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167). Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973). May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960). Involved in both stress and inflammatory responses (By similarity). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity). Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110). Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110). Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110). ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110). May be involved in mitotic chromosome segregation (PubMed:21730191). {ECO:0000250|UniProtKB:Q62167, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17095540, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19913487, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23413191, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:27736973, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:28842590, ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29222110, ECO:0000269|PubMed:30256975, ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:31575075, ECO:0000269|PubMed:33674311, ECO:0000305}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385). {ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960). {ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication. {ECO:0000269|PubMed:27105836}. |
| O14579 | COPE | Y203 | Sugiyama | Coatomer subunit epsilon (Epsilon-coat protein) (Epsilon-COP) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated with ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| O15523 | DDX3Y | Y341 | Sugiyama | ATP-dependent RNA helicase DDX3Y (EC 3.6.4.13) (DEAD box protein 3, Y-chromosomal) | Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway (By similarity). {ECO:0000250|UniProtKB:Q62095}. |
| P07686 | HEXB | Y310 | Sugiyama | Beta-hexosaminidase subunit beta (EC 3.2.1.52) (Beta-N-acetylhexosaminidase subunit beta) (Hexosaminidase subunit B) (Cervical cancer proto-oncogene 7 protein) (HCC-7) (N-acetyl-beta-glucosaminidase subunit beta) [Cleaved into: Beta-hexosaminidase subunit beta chain B; Beta-hexosaminidase subunit beta chain A] | Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides (PubMed:11707436, PubMed:8123671, PubMed:8672428, PubMed:9694901). The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide (PubMed:11707436). Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A (PubMed:8123671, PubMed:8672428, PubMed:9694901). During fertilization is responsible, at least in part, for the zona block to polyspermy. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and inactivates the sperm galactosyltransferase-binding site, accounting for the block in sperm binding to the zona pellucida (By similarity). {ECO:0000250|UniProtKB:P20060, ECO:0000269|PubMed:11707436, ECO:0000269|PubMed:8123671, ECO:0000269|PubMed:8672428, ECO:0000269|PubMed:9694901}. |
| P08243 | ASNS | Y398 | Sugiyama | Asparagine synthetase [glutamine-hydrolyzing] (EC 6.3.5.4) (Cell cycle control protein TS11) (Glutamine-dependent asparagine synthetase) | None |
| P09622 | DLD | Y97 | Sugiyama | Dihydrolipoyl dehydrogenase, mitochondrial (EC 1.8.1.4) (Dihydrolipoamide dehydrogenase) (Glycine cleavage system L protein) | Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity). {ECO:0000250|UniProtKB:Q811C4, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:20385101, ECO:0000269|PubMed:29211711}. |
| P13639 | EEF2 | Y745 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| P25786 | PSMA1 | Y224 | Sugiyama | Proteasome subunit alpha type-1 (30 kDa prosomal protein) (PROS-30) (Macropain subunit C2) (Multicatalytic endopeptidase complex subunit C2) (Proteasome component C2) (Proteasome nu chain) (Proteasome subunit alpha-6) (alpha-6) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P55060 | CSE1L | Y282 | Sugiyama | Exportin-2 (Exp2) (Cellular apoptosis susceptibility protein) (Chromosome segregation 1-like protein) (Importin-alpha re-exporter) | Export receptor for importin-alpha. Mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates (cargos) have been released into the nucleoplasm. In the nucleus binds cooperatively to importin-alpha and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the importin-alpha from the export receptor. CSE1L/XPO2 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. {ECO:0000269|PubMed:9323134}. |
| P60900 | PSMA6 | Y27 | Sugiyama | Proteasome subunit alpha type-6 (27 kDa prosomal protein) (PROS-27) (p27K) (Macropain iota chain) (Multicatalytic endopeptidase complex iota chain) (Proteasome iota chain) (Proteasome subunit alpha-1) (alpha-1) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P62191 | PSMC1 | Y210 | Sugiyama | 26S proteasome regulatory subunit 4 (P26s4) (26S proteasome AAA-ATPase subunit RPT2) (Proteasome 26S subunit ATPase 1) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC1 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798}. |
| P82930 | MRPS34 | Y38 | Sugiyama | Small ribosomal subunit protein mS34 (28S ribosomal protein S34, mitochondrial) (MRP-S34) (S34mt) | Required for mitochondrial translation, plays a role in maintaining the stability of the small ribosomal subunit and the 12S rRNA that are required for mitoribosome formation. {ECO:0000269|PubMed:28777931}. |
| Q13057 | COASY | Y396 | Sugiyama | Bifunctional coenzyme A synthase (CoA synthase) (NBP) (POV-2) [Includes: Phosphopantetheine adenylyltransferase (EC 2.7.7.3) (Dephospho-CoA pyrophosphorylase) (Pantetheine-phosphate adenylyltransferase) (PPAT); Dephospho-CoA kinase (DPCK) (EC 2.7.1.24) (Dephosphocoenzyme A kinase) (DPCOAK)] | Bifunctional enzyme that catalyzes the fourth and fifth sequential steps of CoA biosynthetic pathway. The fourth reaction is catalyzed by the phosphopantetheine adenylyltransferase, coded by the coaD domain; the fifth reaction is catalyzed by the dephospho-CoA kinase, coded by the coaE domain. May act as a point of CoA biosynthesis regulation. {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:24360804}. |
| Q15459 | SF3A1 | Y314 | Sugiyama | Splicing factor 3A subunit 1 (SF3a120) (Spliceosome-associated protein 114) (SAP 114) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10882114, PubMed:11533230, PubMed:32494006). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:10882114, PubMed:11533230, PubMed:32494006). Within the 17S U2 SnRNP complex, SF3A1 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes (PubMed:29360106, PubMed:30315277). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:11533230, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:32494006}. |
| Q16762 | TST | Y37 | Sugiyama | Thiosulfate sulfurtransferase (EC 2.8.1.1) (Rhodanese) | Formation of iron-sulfur complexes, cyanide detoxification or modification of sulfur-containing enzymes. Other thiol compounds, besides cyanide, can act as sulfur ion acceptors. Also has weak mercaptopyruvate sulfurtransferase (MST) activity (By similarity). Together with MRPL18, acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA. {ECO:0000250, ECO:0000269|PubMed:20663881, ECO:0000269|PubMed:21685364}. |
| Q16881 | TXNRD1 | Y338 | Sugiyama | Thioredoxin reductase 1, cytoplasmic (TR) (EC 1.8.1.9) (Gene associated with retinoic and interferon-induced mortality 12 protein) (GRIM-12) (Gene associated with retinoic and IFN-induced mortality 12 protein) (KM-102-derived reductase-like factor) (Peroxidase TXNRD1) (EC 1.11.1.2) (Thioredoxin reductase TR1) | Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form (PubMed:8577704). Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (Probable). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). {ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:8577704, ECO:0000305|PubMed:17512005}.; FUNCTION: [Isoform 1]: Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. {ECO:0000269|PubMed:18042542, ECO:0000269|PubMed:8577704}.; FUNCTION: [Isoform 4]: Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2. {ECO:0000269|PubMed:15199063}.; FUNCTION: [Isoform 5]: Enhances the transcriptional activity of the estrogen receptor ESR2 only (PubMed:15199063). Mediates cell death induced by a combination of interferon-beta and retinoic acid (PubMed:9774665). {ECO:0000269|PubMed:15199063, ECO:0000269|PubMed:9774665}. |
| Q8WVJ2 | NUDCD2 | Y108 | Sugiyama | NudC domain-containing protein 2 | May regulate the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. {ECO:0000269|PubMed:20133715}. |
| Q9BZX2 | UCK2 | Y203 | Sugiyama | Uridine-cytidine kinase 2 (UCK 2) (EC 2.7.1.48) (Cytidine monophosphokinase 2) (Testis-specific protein TSA903) (Uridine monophosphokinase 2) | Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate (PubMed:11306702, PubMed:11494055). Does not phosphorylate deoxyribonucleosides or purine ribonucleosides (PubMed:11306702). Can use ATP or GTP as a phosphate donor (PubMed:11306702). Can also phosphorylate cytidine and uridine nucleoside analogs such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine (PubMed:11306702). {ECO:0000269|PubMed:11306702, ECO:0000269|PubMed:11494055}. |
| Q9HA47 | UCK1 | Y205 | Sugiyama | Uridine-cytidine kinase 1 (UCK 1) (EC 2.7.1.48) (Cytidine monophosphokinase 1) (Uridine monophosphokinase 1) | Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate (PubMed:11306702). Does not phosphorylate deoxyribonucleosides or purine ribonucleosides (PubMed:11306702). Can use ATP or GTP as a phosphate donor (PubMed:11306702). Can also phosphorylate cytidine and uridine nucleoside analogs such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine (PubMed:11306702). {ECO:0000269|PubMed:11306702}. |
| Q9NQI0 | DDX4 | Y442 | Sugiyama | Probable ATP-dependent RNA helicase DDX4 (EC 3.6.4.13) (DEAD box protein 4) (Vasa homolog) | ATP-dependent RNA helicase required during spermatogenesis (PubMed:10920202, PubMed:21034600). Required to repress transposable elements and preventing their mobilization, which is essential for the germline integrity (By similarity). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (By similarity). Involved in the secondary piRNAs metabolic process, the production of piRNAs in fetal male germ cells through a ping-pong amplification cycle (By similarity). Required for PIWIL2 slicing-triggered piRNA biogenesis: helicase activity enables utilization of one of the slice cleavage fragments generated by PIWIL2 and processing these pre-piRNAs into piRNAs (By similarity). {ECO:0000250|UniProtKB:Q61496, ECO:0000269|PubMed:10920202, ECO:0000269|PubMed:21034600}. |
| P07333 | CSF1R | Y873 | Sugiyama | Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms) (CD antigen CD115) | Tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of pro-inflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608). {ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, ECO:0000269|PubMed:30982608, ECO:0000269|PubMed:30982609, ECO:0000269|PubMed:7683918}. |
| O00429 | DNM1L | Y691 | Sugiyama | Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1) | Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:19411255, PubMed:19638400, PubMed:23283981, PubMed:23530241, PubMed:23921378, PubMed:26992161, PubMed:27145208, PubMed:27145933, PubMed:27301544, PubMed:27328748, PubMed:29478834, PubMed:32439975, PubMed:32484300, PubMed:9570752, PubMed:9786947). Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism (PubMed:23530241, PubMed:23584531, PubMed:33850055). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:23921378, PubMed:29899447). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:29899447). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity). Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:26992161, PubMed:27145208, PubMed:27301544, PubMed:27328748). Facilitates developmentally regulated apoptosis during neural tube formation (By similarity). Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues (By similarity). Required for formation of endocytic vesicles (PubMed:20688057, PubMed:23792689, PubMed:9570752). Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (PubMed:17015472, PubMed:23792689). Required for programmed necrosis execution (PubMed:22265414). Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834). {ECO:0000250|UniProtKB:Q8K1M6, ECO:0000269|PubMed:11514614, ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:17015472, ECO:0000269|PubMed:17301055, ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:17553808, ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19342591, ECO:0000269|PubMed:19411255, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:20688057, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531, ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:29899447, ECO:0000269|PubMed:32439975, ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9786947}.; FUNCTION: [Isoform 1]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}.; FUNCTION: [Isoform 4]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}. |
| P09917 | ALOX5 | Y43 | PSP | Polyunsaturated fatty acid 5-lipoxygenase (EC 1.13.11.-) (Arachidonate 5-lipoxygenase) (5-LO) (5-lipoxygenase) (EC 1.13.11.34) | Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:8615788). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity). {ECO:0000250|UniProtKB:P48999, ECO:0000269|PubMed:17114001, ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:21200133, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:21233389, ECO:0000269|PubMed:22516296, ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:31664810, ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361}. |
| P26640 | VARS1 | Y24 | Sugiyama | Valine--tRNA ligase (EC 6.1.1.9) (Protein G7a) (Valyl-tRNA synthetase) (ValRS) | Catalyzes the attachment of valine to tRNA(Val). {ECO:0000269|PubMed:8428657}. |
| Q96DB5 | RMDN1 | Y92 | Sugiyama | Regulator of microtubule dynamics protein 1 (RMD-1) (hRMD-1) (Protein FAM82B) | None |
| O15355 | PPM1G | Y74 | Sugiyama | Protein phosphatase 1G (EC 3.1.3.16) (Protein phosphatase 1C) (Protein phosphatase 2C isoform gamma) (PP2C-gamma) (Protein phosphatase magnesium-dependent 1 gamma) | None |
| P14625 | HSP90B1 | Y563 | Sugiyama | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P17844 | DDX5 | Y244 | Sugiyama | Probable ATP-dependent RNA helicase DDX5 (EC 3.6.4.13) (DEAD box protein 5) (RNA helicase p68) | Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as a transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. {ECO:0000269|PubMed:12527917, ECO:0000269|PubMed:15298701, ECO:0000269|PubMed:15660129, ECO:0000269|PubMed:17011493, ECO:0000269|PubMed:17960593, ECO:0000269|PubMed:18829551, ECO:0000269|PubMed:19718048, ECO:0000269|PubMed:21343338}. |
| P80303 | NUCB2 | Y57 | Sugiyama | Nucleobindin-2 (DNA-binding protein NEFA) (Epididymis secretory protein Li 109) (Gastric cancer antigen Zg4) (Prepronesfatin) [Cleaved into: Nesfatin-1] | Calcium-binding protein which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3 (By similarity). {ECO:0000250|UniProtKB:P81117, ECO:0000250|UniProtKB:Q9JI85}.; FUNCTION: [Nesfatin-1]: Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance. In intestinal epithelial cells, plays a role in the inhibition of hepatic glucose production via MC4R receptor leading to increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion (PubMed:39562740). {ECO:0000250|UniProtKB:Q9JI85, ECO:0000269|PubMed:39562740}. |
| Q14974 | KPNB1 | Y156 | Sugiyama | Importin subunit beta-1 (Importin-90) (Karyopherin subunit beta-1) (Nuclear factor p97) (Pore targeting complex 97 kDa subunit) (PTAC97) | Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). Acting autonomously, serves itself as NLS receptor (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:24699649, PubMed:7615630, PubMed:9687515). Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607, PubMed:9687515). In association with IPO7, mediates the nuclear import of H1 histone (PubMed:10228156). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (By similarity). Imports MRTFA, SNAI1 and PRKCI into the nucleus (PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649). {ECO:0000250|UniProtKB:P70168, ECO:0000269|PubMed:10228156, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:19386897, ECO:0000269|PubMed:20818336, ECO:0000269|PubMed:24699649, ECO:0000269|PubMed:7615630, ECO:0000269|PubMed:9687515}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000269|PubMed:16704975, ECO:0000269|PubMed:9405152, ECO:0000269|PubMed:9891055}. |
| Q9P2N5 | RBM27 | Y73 | Sugiyama | RNA-binding protein 27 (RNA-binding motif protein 27) | May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}. |
| P08581 | MET | Y1307 | Sugiyama | Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}. |
| P26358 | DNMT1 | Y973 | Sugiyama | DNA (cytosine-5)-methyltransferase 1 (Dnmt1) (EC 2.1.1.37) (CXXC-type zinc finger protein 9) (DNA methyltransferase HsaI) (DNA MTase HsaI) (M.HsaI) (MCMT) | Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. 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). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306). {ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18754681, ECO:0000269|PubMed:24623306}. |
| P62841 | RPS15 | Y30 | Sugiyama | Small ribosomal subunit protein uS19 (40S ribosomal protein S15) (RIG protein) | 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). {ECO:0000269|PubMed:23636399}. |
| P14550 | AKR1A1 | Y210 | Sugiyama | Aldo-keto reductase family 1 member A1 (EC 1.1.1.2) (EC 1.1.1.372) (EC 1.1.1.54) (Alcohol dehydrogenase [NADP(+)]) (Aldehyde reductase) (Glucuronate reductase) (EC 1.1.1.19) (Glucuronolactone reductase) (EC 1.1.1.20) (S-nitroso-CoA reductase) (ScorR) (EC 1.6.-.-) | Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:10510318, PubMed:30538128). Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (PubMed:10510318, PubMed:30538128). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes (By similarity). Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity). Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN) (PubMed:11306097, PubMed:18276838). Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (PubMed:30538128). S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (PubMed:31649033). Displays no reductase activity towards retinoids (By similarity). {ECO:0000250|UniProtKB:P50578, ECO:0000250|UniProtKB:P51635, ECO:0000269|PubMed:10510318, ECO:0000269|PubMed:11306097, ECO:0000269|PubMed:18276838, ECO:0000269|PubMed:30538128, ECO:0000269|PubMed:31649033}. |
| P09619 | PDGFRB | Y966 | Sugiyama | Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b) | Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11331881, ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:1653029, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:1846866, ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:20529858, ECO:0000269|PubMed:21098708, ECO:0000269|PubMed:21679854, ECO:0000269|PubMed:21733313, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:26599395, ECO:0000269|PubMed:2835772, ECO:0000269|PubMed:2850496, ECO:0000269|PubMed:7685273, ECO:0000269|PubMed:7691811, ECO:0000269|PubMed:7692233, ECO:0000269|PubMed:8195171}. |
| P10721 | KIT | Y553 | EPSD|PSP|Sugiyama | Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117) | Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12511554, ECO:0000269|PubMed:12878163, ECO:0000269|PubMed:17904548, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:9528781}. |
| P22607 | FGFR3 | Y599 | Sugiyama | Fibroblast growth factor receptor 3 (FGFR-3) (EC 2.7.10.1) (CD antigen CD333) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14534538, ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:8663044}. |
| O75643 | SNRNP200 | Y361 | Sugiyama | U5 small nuclear ribonucleoprotein 200 kDa helicase (EC 3.6.4.13) (Activating signal cointegrator 1 complex subunit 3-like 1) (BRR2 homolog) (U5 snRNP-specific 200 kDa protein) (U5-200KD) | Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome (PubMed:35241646). Plays a role in pre-mRNA splicing as a core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154, PubMed:30728453). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:23045696, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:35241646, ECO:0000269|PubMed:8670905, ECO:0000269|PubMed:9539711, ECO:0000305|PubMed:33509932}. |
| P14868 | DARS1 | Y384 | Sugiyama | Aspartate--tRNA ligase, cytoplasmic (EC 6.1.1.12) (Aspartyl-tRNA synthetase) (AspRS) (Cell proliferation-inducing gene 40 protein) | Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. {ECO:0000250|UniProtKB:P15178}. |
| P50542 | PEX5 | Y320 | Sugiyama | Peroxisomal targeting signal 1 receptor (PTS1 receptor) (PTS1R) (PTS1-BP) (Peroxin-5) (Peroxisomal C-terminal targeting signal import receptor) (Peroxisome receptor 1) | Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) (PubMed:11101887, PubMed:11336669, PubMed:12456682, PubMed:16314507, PubMed:17157249, PubMed:17428317, PubMed:21976670, PubMed:26344566, PubMed:7706321, PubMed:7719337, PubMed:7790377). Binds to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, and translocates them into the peroxisome matrix by passing through the PEX13-PEX14 docking complex along with cargo proteins (PubMed:12456682, PubMed:17157249, PubMed:21976670, PubMed:26344566). PEX5 receptor is then retrotranslocated into the cytosol, leading to release of bound cargo in the peroxisome matrix, and reset for a subsequent peroxisome import cycle (PubMed:11336669, PubMed:24662292). {ECO:0000269|PubMed:11101887, ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:12456682, ECO:0000269|PubMed:16314507, ECO:0000269|PubMed:17157249, ECO:0000269|PubMed:17428317, ECO:0000269|PubMed:21976670, ECO:0000269|PubMed:24662292, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:7706321, ECO:0000269|PubMed:7719337, ECO:0000269|PubMed:7790377}.; FUNCTION: [Isoform 1]: In addition to promoting peroxisomal translocation of proteins containing a PTS1 peroxisomal targeting signal, mediates peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal via its interaction with PEX7 (PubMed:11336669, PubMed:11546814, PubMed:25538232, PubMed:33389129, PubMed:9668159). Interaction with PEX7 only takes place when PEX7 is associated with cargo proteins containing a PTS2 peroxisomal targeting signal (PubMed:25538232). PEX7 along with PTS2-containing cargo proteins are then translocated through the PEX13-PEX14 docking complex together with PEX5 (PubMed:25538232). {ECO:0000269|PubMed:11336669, ECO:0000269|PubMed:11546814, ECO:0000269|PubMed:25538232, ECO:0000269|PubMed:33389129, ECO:0000269|PubMed:9668159}.; FUNCTION: [Isoform 2]: Does not mediate translocation of peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal. {ECO:0000269|PubMed:11546814}. |
| Q04917 | YWHAH | Y216 | Sugiyama | 14-3-3 protein eta (Protein AS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| Q13867 | BLMH | Y288 | Sugiyama | Bleomycin hydrolase (BH) (BLM hydrolase) (BMH) (EC 3.4.22.40) | The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity. {ECO:0000250}. |
| Q99504 | EYA3 | Y208 | PSP | Protein phosphatase EYA3 (EC 3.1.3.48) (Eyes absent homolog 3) | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye. {ECO:0000250|UniProtKB:P97480, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884}. |
| Q99504 | EYA3 | Y325 | PSP | Protein phosphatase EYA3 (EC 3.1.3.48) (Eyes absent homolog 3) | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye. {ECO:0000250|UniProtKB:P97480, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884}. |
| P78417 | GSTO1 | Y108 | Sugiyama | Glutathione S-transferase omega-1 (GSTO-1) (EC 2.5.1.18) (Glutathione S-transferase omega 1-1) (GSTO 1-1) (Glutathione-dependent dehydroascorbate reductase) (EC 1.8.5.1) (Monomethylarsonic acid reductase) (MMA(V) reductase) (EC 1.20.4.2) (S-(Phenacyl)glutathione reductase) (SPG-R) | Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Also has glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. {ECO:0000269|PubMed:10783391, ECO:0000269|PubMed:11511179, ECO:0000269|PubMed:17226937, ECO:0000269|PubMed:18028863, ECO:0000269|PubMed:21106529}. |
| Q13501 | SQSTM1 | Y422 | Sugiyama | Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) | Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}. |
| Q99615 | DNAJC7 | Y279 | Sugiyama | DnaJ homolog subfamily C member 7 (Tetratricopeptide repeat protein 2) (TPR repeat protein 2) | Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recycling chaperone by facilitating the return of chaperone substrates to early stages of chaperoning if further folding is required. In vitro, induces ATP-independent dissociation of HSP90 but not of HSP70 from the chaperone-substrate complexes. Recruits NR1I3 to the cytoplasm (By similarity). {ECO:0000250, ECO:0000269|PubMed:12853476, ECO:0000269|PubMed:18620420}. |
| Q9NUQ3 | TXLNG | Y100 | Sugiyama | Gamma-taxilin (Environmental lipopolysaccharide-responding gene protein) (Factor inhibiting ATF4-mediated transcription) (FIAT) (Lipopolysaccharide-specific response protein 5) | May be involved in intracellular vesicle traffic. Inhibits ATF4-mediated transcription, possibly by dimerizing with ATF4 to form inactive dimers that cannot bind DNA. May be involved in regulating bone mass density through an ATF4-dependent pathway. May be involved in cell cycle progression. {ECO:0000269|PubMed:15911876, ECO:0000269|PubMed:18068885}. |
| P62714 | PPP2CB | Y86 | Sugiyama | Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform (PP2A-beta) (EC 3.1.3.16) | Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events (Probable). PP2A can modulate the activity of phosphorylase B kinase, casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:2555176, ECO:0000305}. |
| P67775 | PPP2CA | Y86 | Sugiyama | Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PP2A-alpha) (EC 3.1.3.16) (Replication protein C) (RP-C) | Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events (PubMed:10801873, PubMed:12473674, PubMed:17245430, PubMed:22613722, PubMed:33243860, PubMed:34004147, PubMed:9920888). PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (PubMed:22613722). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (PubMed:22613722). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate various proteins, such as SV40 large T antigen, AXIN1, p53/TP53, PIM3, WEE1 (PubMed:10801873, PubMed:12473674, PubMed:17245430, PubMed:9920888). Activates RAF1 by dephosphorylating it at 'Ser-259' (PubMed:10801873). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758). Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (PubMed:25438055). Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (PubMed:30513302). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity). Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (By similarity). Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (By similarity). Catalyzes dephosphorylation of PIM3, promotinh PIM3 ubiquitination and proteasomal degradation (PubMed:12473674). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:33633399). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling (PubMed:33633399). Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:33633399). Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex (PubMed:33243860, PubMed:34004147, PubMed:37080207). The INTAC complex drives premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: within the INTAC complex, PPP2CA catalyzes dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, thereby preventing transcriptional elongation (PubMed:33243860, PubMed:34004147, PubMed:37080207). {ECO:0000250|UniProtKB:P63330, ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:12473674, ECO:0000269|PubMed:17245430, ECO:0000269|PubMed:22613722, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:30513302, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:33633399, ECO:0000269|PubMed:34004147, ECO:0000269|PubMed:37080207, ECO:0000269|PubMed:9920888}. |
| O60282 | KIF5C | Y229 | Sugiyama | Kinesin heavy chain isoform 5C (EC 3.6.4.-) (Kinesin heavy chain neuron-specific 2) (Kinesin-1) | Microtubule-associated force-producing protein that may play a role in organelle transport. Has ATPase activity (By similarity). Involved in synaptic transmission (PubMed:24812067). Mediates dendritic trafficking of mRNAs (By similarity). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). {ECO:0000250|UniProtKB:P28738, ECO:0000250|UniProtKB:P56536, ECO:0000269|PubMed:24812067}. |
| P21802 | FGFR2 | Y608 | Sugiyama | Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD antigen CD332) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. {ECO:0000269|PubMed:12529371, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:15629145, ECO:0000269|PubMed:16384934, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19103595, ECO:0000269|PubMed:19387476, ECO:0000269|PubMed:19410646, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:8663044}. |
| P33176 | KIF5B | Y228 | Sugiyama | Kinesin-1 heavy chain (Conventional kinesin heavy chain) (Ubiquitous kinesin heavy chain) (UKHC) | Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). {ECO:0000250|UniProtKB:Q2PQA9, ECO:0000250|UniProtKB:Q61768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:24088571, ECO:0000305|PubMed:22172677, ECO:0000305|PubMed:24088571}. |
| Q12840 | KIF5A | Y229 | Sugiyama | Kinesin heavy chain isoform 5A (EC 5.6.1.3) (Kinesin heavy chain neuron-specific 1) (Neuronal kinesin heavy chain) (NKHC) | Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 proteins in neurons. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation. {ECO:0000250|UniProtKB:P33175, ECO:0000250|UniProtKB:Q6QLM7}. |
| Q9NQA5 | TRPV5 | Y647 | Sugiyama | Transient receptor potential cation channel subfamily V member 5 (TrpV5) (Calcium transport protein 2) (CaT2) (Epithelial calcium channel 1) (ECaC) (ECaC1) (Osm-9-like TRP channel 3) (OTRPC3) | Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:11549322, PubMed:18768590). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (PubMed:11549322, PubMed:18768590). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity). {ECO:0000250|UniProtKB:P69744, ECO:0000250|UniProtKB:Q9XSM3, ECO:0000269|PubMed:11549322, ECO:0000269|PubMed:18768590}. |
| Q13573 | SNW1 | Y176 | Sugiyama | SNW domain-containing protein 1 (Nuclear protein SkiP) (Nuclear receptor coactivator NCoA-62) (Ski-interacting protein) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. {ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:11514567, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12840015, ECO:0000269|PubMed:14985122, ECO:0000269|PubMed:15194481, ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:19818711, ECO:0000269|PubMed:21245387, ECO:0000269|PubMed:21460037, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:9632709, ECO:0000305|PubMed:33509932}.; FUNCTION: (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. {ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:19818711}.; FUNCTION: (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. {ECO:0000269|PubMed:10644367}. |
| O43707 | ACTN4 | Y485 | Sugiyama | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| P54756 | EPHA5 | Y796 | Sugiyama | Ephrin type-A receptor 5 (EC 2.7.10.1) (Brain-specific kinase) (EPH homology kinase 1) (EHK-1) (EPH-like kinase 7) (EK7) (hEK7) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion (By similarity). {ECO:0000250}. |
| P11047 | LAMC1 | Y275 | Sugiyama | Laminin subunit gamma-1 (Laminin B2 chain) (Laminin-1 subunit gamma) (Laminin-10 subunit gamma) (Laminin-11 subunit gamma) (Laminin-2 subunit gamma) (Laminin-3 subunit gamma) (Laminin-4 subunit gamma) (Laminin-6 subunit gamma) (Laminin-7 subunit gamma) (Laminin-8 subunit gamma) (Laminin-9 subunit gamma) (S-laminin subunit gamma) (S-LAM gamma) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. |
| P15531 | NME1 | Y52 | Sugiyama | Nucleoside diphosphate kinase A (NDK A) (NDP kinase A) (EC 2.7.4.6) (Granzyme A-activated DNase) (GAAD) (Metastasis inhibition factor nm23) (NM23-H1) (Tumor metastatic process-associated protein) | Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair. {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:8810265}. |
| P33993 | MCM7 | Y297 | Sugiyama | DNA replication licensing factor MCM7 (EC 3.6.4.12) (CDC47 homolog) (P1.1-MCM3) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for S-phase checkpoint activation upon UV-induced damage. {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:25661590, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| P61923 | COPZ1 | Y31 | Sugiyama | Coatomer subunit zeta-1 (Zeta-1-coat protein) (Zeta-1 COP) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins (By similarity). The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex (By similarity). {ECO:0000250|UniProtKB:P53600}. |
| Q14204 | DYNC1H1 | Y1889 | Sugiyama | Cytoplasmic dynein 1 heavy chain 1 (Cytoplasmic dynein heavy chain 1) (Dynein heavy chain, cytosolic) | Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074). {ECO:0000269|PubMed:27462074}. |
| P29323 | EPHB2 | Y742 | Sugiyama | Ephrin type-B receptor 2 (EC 2.7.10.1) (Developmentally-regulated Eph-related tyrosine kinase) (ELK-related tyrosine kinase) (EPH tyrosine kinase 3) (EPH-like kinase 5) (EK5) (hEK5) (Renal carcinoma antigen NY-REN-47) (Tyrosine-protein kinase TYRO5) (Tyrosine-protein kinase receptor EPH-3) [Cleaved into: EphB2/CTF1; EphB2/CTF2] | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874). {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:30213874}. |
| Q96PU8 | QKI | Y87 | Sugiyama | KH domain-containing RNA-binding protein QKI (Protein quaking) (Hqk) (HqkI) | RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and/or translation (PubMed:22398723, PubMed:23630077, PubMed:25768908, PubMed:27029405, PubMed:31331967, PubMed:37379838). Involved in various cellular processes, such as mRNA storage into stress granules, apoptosis, lipid deposition, interferon response, glial cell fate and development (PubMed:25768908, PubMed:31829086, PubMed:34428287, PubMed:37379838). Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence (PubMed:23630077). Acts as a mRNA modification reader that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (PubMed:37379838). Promotes the formation of circular RNAs (circRNAs) during the epithelial to mesenchymal transition and in cardiomyocytes: acts by binding to sites flanking circRNA-forming exons (PubMed:25768908). CircRNAs are produced by back-splicing circularization of pre-mRNAs (PubMed:25768908). Plays a central role in myelinization via 3 distinct mechanisms (PubMed:16641098). First, acts by protecting and promoting stability of target mRNAs such as MBP, SIRT2 and CDKN1B, which promotes oligodendrocyte differentiation (By similarity). Second, participates in mRNA transport by regulating the nuclear export of MBP mRNA (By similarity). Finally, indirectly regulates mRNA splicing of MAG pre-mRNA during oligodendrocyte differentiation by acting as a negative regulator of MAG exon 12 alternative splicing: acts by binding to HNRNPA1 mRNA splicing factor, preventing its translation (By similarity). Involved in microglia differentiation and remyelination by regulating microexon alternative splicing of the Rho GTPase pathway (By similarity). Involved in macrophage differentiation: promotes monocyte differentiation by regulating pre-mRNA splicing in naive peripheral blood monocytes (PubMed:27029405). Acts as an important regulator of muscle development: required for the contractile function of cardiomyocytes by regulating alternative splicing of cardiomyocyte transcripts (By similarity). Acts as a negative regulator of thermogenesis by decreasing stability, nuclear export and translation of mRNAs encoding PPARGC1A and UCP1 (By similarity). Also required for visceral endoderm function and blood vessel development (By similarity). May also play a role in smooth muscle development (PubMed:31331967). In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2 (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:16641098, ECO:0000269|PubMed:22398723, ECO:0000269|PubMed:23630077, ECO:0000269|PubMed:25768908, ECO:0000269|PubMed:27029405, ECO:0000269|PubMed:31331967, ECO:0000269|PubMed:31829086, ECO:0000269|PubMed:34428287, ECO:0000269|PubMed:37379838}.; FUNCTION: [Isoform QKI5]: Nuclear isoform that acts as an indirect regulator of mRNA splicing (By similarity). Regulates mRNA splicing of MAG pre-mRNA by inhibiting translation of HNRNPA1 mRNA, thereby preventing MAG exon 12 alternative splicing (By similarity). Involved in oligodendrocyte differentiation by promoting stabilization of SIRT2 mRNA (By similarity). Acts as a negative regulator of the interferon response by binding to MAVS mRNA, downregulating its expression (PubMed:31829086). Also inhibits the interferon response by binding to fibrinectin FN1 pre-mRNA, repressing EDA exon inclusion in FN1 (PubMed:34428287). Delays macrophage differentiation by binding to CSF1R mRNA, promoting its degradation (PubMed:22398723). In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2, promoting SREBF2/SREBP2-dependent cholesterol biosynthesis (By similarity). SREBF2/SREBP2-dependent cholesterol biosynthesis participates to myelinization and is required for eye lens transparency (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:22398723, ECO:0000269|PubMed:31829086, ECO:0000269|PubMed:34428287}.; FUNCTION: [Isoform QKI6]: Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (PubMed:37379838). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation (PubMed:37379838). Acts as a translational repressor for HNRNPA1 and GLI1 (By similarity). Translation inhibition of HNRNPA1 during oligodendrocyte differentiation prevents inclusion of exon 12 in MAG pre-mRNA splicing (By similarity). Involved in astrocyte differentiation by regulating translation of target mRNAs (By similarity). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:37379838}.; FUNCTION: [Isoform QKI7]: Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (PubMed:37379838). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation (PubMed:37379838). Acts as a negative regulator of angiogenesis by binding to mRNAs encoding CDH5, NLGN1 and TNFAIP6, promoting their degradation (PubMed:32732889). Can also induce apoptosis in the cytoplasm (By similarity). Heterodimerization with other isoforms results in nuclear translocation of isoform QKI7 and suppression of apoptosis (By similarity). Also binds some microRNAs: promotes stabilitation of miR-122 by mediating recruitment of poly(A) RNA polymerase TENT2, leading to 3' adenylation and stabilization of miR-122 (PubMed:31792053). {ECO:0000250|UniProtKB:Q9QYS9, ECO:0000269|PubMed:31792053, ECO:0000269|PubMed:32732889, ECO:0000269|PubMed:37379838}. |
| O15371 | EIF3D | Y184 | Sugiyama | Eukaryotic translation initiation factor 3 subunit D (eIF3d) (Eukaryotic translation initiation factor 3 subunit 7) (eIF-3-zeta) (eIF3 p66) | mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815). {ECO:0000269|PubMed:18599441, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| Q6IBS0 | TWF2 | Y134 | Sugiyama | Twinfilin-2 (A6-related protein) (hA6RP) (Protein tyrosine kinase 9-like) (Twinfilin-1-like protein) | Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles. May play a role in regulating the mature length of the middle and short rows of stereocilia (By similarity). {ECO:0000250}. |
| Q9C0C2 | TNKS1BP1 | Y1571 | Sugiyama | 182 kDa tankyrase-1-binding protein | None |
| P43405 | SYK | Y507 | Sugiyama | Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) (p72-Syk) | Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:34634301, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}. |
| Q96RT6 | CTAGE1 | Y73 | Sugiyama | cTAGE family member 2 (Protein cTAGE-2) (Cancer/testis antigen 21.2) (CT21.2) | None |
| P51813 | BMX | Y43 | Sugiyama | Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) | Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}. |
| P51813 | BMX | Y613 | Sugiyama | Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) | Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}. |
| Q6UUV9 | CRTC1 | Y50 | Sugiyama | CREB-regulated transcription coactivator 1 (Mucoepidermoid carcinoma translocated protein 1) (Transducer of regulated cAMP response element-binding protein 1) (TORC-1) (Transducer of CREB protein 1) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons (By similarity). In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock. {ECO:0000250|UniProtKB:Q157S1, ECO:0000250|UniProtKB:Q68ED7, ECO:0000269|PubMed:23699513}.; FUNCTION: (Microbial infection) Plays a role of coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:16809310}. |
| Q9C0D5 | TANC1 | Y327 | Sugiyama | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9Y2G5 | POFUT2 | Y228 | Sugiyama | GDP-fucose protein O-fucosyltransferase 2 (EC 2.4.1.221) (Peptide-O-fucosyltransferase 2) (O-FucT-2) | Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue in the consensus sequence C1-X-X-S/T-C2 of thrombospondin type I repeats (TSRs) where C1 and C2 are the first and second cysteines of the repeat, respectively (PubMed:22588082). O-fucosylates members of several protein families including the ADAMTS, the thrombospondin (TSP) and spondin families (Probable) (PubMed:17395588). Required for the proper secretion of ADAMTS family members such as ADAMTSL1 and ADAMTS13 (PubMed:17395588, PubMed:17395589). The O-fucosylation of TSRs is also required for restricting epithelial to mesenchymal transition (EMT), maintaining the correct patterning of mesoderm and localization of the definite endoderm (By similarity). {ECO:0000250|UniProtKB:Q8VHI3, ECO:0000269|PubMed:17395588, ECO:0000269|PubMed:17395589, ECO:0000269|PubMed:22588082, ECO:0000305|PubMed:11067851, ECO:0000305|PubMed:16464858}. |
| P54753 | EPHB3 | Y754 | Sugiyama | Ephrin type-B receptor 3 (EC 2.7.10.1) (EPH-like tyrosine kinase 2) (EPH-like kinase 2) (Embryonic kinase 2) (EK2) (hEK2) (Tyrosine-protein kinase TYRO6) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt. {ECO:0000269|PubMed:15536074}. |
| Q92973 | TNPO1 | Y150 | Sugiyama | Transportin-1 (Importin beta-2) (Karyopherin beta-2) (M9 region interaction protein) (MIP) | Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates (PubMed:24753571). May mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (By similarity). In vitro, mediates nuclear import of SRP19 (PubMed:11682607). Mediates nuclear import of ADAR/ADAR1 isoform 1 and isoform 5 in a RanGTP-dependent manner (PubMed:19124606, PubMed:24753571). Main mediator of PR-DUB complex component BAP1 nuclear import; acts redundantly with the karyopherins KPNA1 and KPNA2 (PubMed:35446349). {ECO:0000250|UniProtKB:Q8BFY9, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:19124606, ECO:0000269|PubMed:24753571, ECO:0000269|PubMed:35446349, ECO:0000269|PubMed:8986607, ECO:0000269|PubMed:9687515}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000269|PubMed:16704975}. |
| P54760 | EPHB4 | Y736 | Sugiyama | Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}. |
| Q15436 | SEC23A | Y56 | Sugiyama | Protein transport protein Sec23A (hSec23A) (SEC23-related protein A) | Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex. Required for the translocation of insulin-induced glucose transporter SLC2A4/GLUT4 to the cell membrane (By similarity). {ECO:0000250|UniProtKB:Q01405, ECO:0000269|PubMed:16980979, ECO:0000269|PubMed:17499046, ECO:0000269|PubMed:18843296, ECO:0000269|PubMed:27551091, ECO:0000269|PubMed:8898360}. |
| P26639 | TARS1 | Y351 | Sugiyama | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P54762 | EPHB1 | Y740 | Sugiyama | Ephrin type-B receptor 1 (EC 2.7.10.1) (ELK) (EPH tyrosine kinase 2) (EPH-like kinase 6) (EK6) (hEK6) (Neuronally-expressed EPH-related tyrosine kinase) (NET) (Tyrosine-protein kinase receptor EPH-2) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}. |
| P54764 | EPHA4 | Y742 | Sugiyama | Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK) | Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (By similarity). {ECO:0000250|UniProtKB:Q03137, ECO:0000269|PubMed:17143272}. |
| Q02763 | TEK | Y976 | Sugiyama | Angiopoietin-1 receptor (EC 2.7.10.1) (Endothelial tyrosine kinase) (Tunica interna endothelial cell kinase) (Tyrosine kinase with Ig and EGF homology domains-2) (Tyrosine-protein kinase receptor TEK) (Tyrosine-protein kinase receptor TIE-2) (hTIE2) (p140 TEK) (CD antigen CD202b) | Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1. {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}. |
| Q06187 | BTK | Y42 | Sugiyama | Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) | Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}. |
| P12277 | CKB | Y174 | Sugiyama | Creatine kinase B-type (EC 2.7.3.2) (Brain creatine kinase) (B-CK) (Creatine kinase B chain) (Creatine phosphokinase B-type) (CPK-B) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity). {ECO:0000250|UniProtKB:Q04447, ECO:0000269|PubMed:8186255, ECO:0000305}. |
| P18669 | PGAM1 | Y50 | Sugiyama | Phosphoglycerate mutase 1 (EC 5.4.2.11) (EC 5.4.2.4) (BPG-dependent PGAM 1) (Phosphoglycerate mutase isozyme B) (PGAM-B) | Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate (PubMed:23653202). Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate (PubMed:23653202). {ECO:0000269|PubMed:23653202}. |
| Q14444 | CAPRIN1 | Y190 | Sugiyama | Caprin-1 (Cell cycle-associated protein 1) (Cytoplasmic activation- and proliferation-associated protein 1) (GPI-anchored membrane protein 1) (GPI-anchored protein p137) (GPI-p137) (p137GPI) (Membrane component chromosome 11 surface marker 1) (RNA granule protein 105) | mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in neurogenesis, synaptic plasticity in neurons and cell proliferation and migration in multiple cell types (PubMed:17210633, PubMed:31439799, PubMed:35979925). Plays an essential role in cytoplasmic stress granule formation (PubMed:35977029). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:31439799, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34074792, PubMed:36040869, PubMed:36279435). Undergoes liquid-liquid phase separation following phosphorylation and interaction with FMR1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (PubMed:31439799). In these cytoplasmic ribonucleoprotein granules, CAPRIN1 mediates recruitment of CNOT7 deadenylase, leading to mRNA deadenylation and degradation (PubMed:31439799). Binds directly and selectively to MYC and CCND2 mRNAs (PubMed:17210633). In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs (PubMed:17210633). {ECO:0000269|PubMed:17210633, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:34074792, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:35979925, ECO:0000269|PubMed:36040869, ECO:0000269|PubMed:36279435}. |
| Q12866 | MERTK | Y676 | Sugiyama | Tyrosine-protein kinase Mer (EC 2.7.10.1) (Proto-oncogene c-Mer) (Receptor tyrosine kinase MerTK) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment (PubMed:32640697). Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:32640697}. |
| Q13233 | MAP3K1 | Y1359 | Sugiyama | Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1) (EC 2.3.2.27) | Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). {ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:9808624}. |
| O75390 | CS | Y381 | Sugiyama | Citrate synthase, mitochondrial (EC 2.3.3.1) (Citrate (Si)-synthase) | Key enzyme of the Krebs tricarboxylic acid cycle which catalyzes the synthesis of citrate from acetyl coenzyme A and oxaloacetate. {ECO:0000305}. |
| Q6GQQ9 | OTUD7B | Y384 | Sugiyama | OTU domain-containing protein 7B (EC 3.4.19.12) (Cellular zinc finger anti-NF-kappa-B protein) (Cezanne) (Zinc finger A20 domain-containing protein 1) (Zinc finger protein Cezanne) | Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses (PubMed:18178551). In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (By similarity). Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:11463333, PubMed:20622874, PubMed:23827681, PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin (PubMed:12682062). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked deubiquitination of MLST8, thereby promoting assembly of the mTORC2 complex, while inibiting formation of the mTORC1 complex (PubMed:28489822). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584, ECO:0000269|PubMed:28489822}. |
| Q9NVN3 | RIC8B | Y445 | Sugiyama | Chaperone Ric-8B (Brain synembryn) (hSyn) (Synembryn-B) | Chaperone that specifically binds and folds nascent G(s) G-alpha proteins (GNAS and GNAL) prior to G protein heterotrimer formation, promoting their association with the plasma membrane (By similarity). Also acts as a guanine nucleotide exchange factor (GEF) for G(s) proteins by stimulating exchange of bound GDP for free GTP (By similarity). Acts as an important component for odorant signal transduction by mediating GNAL (G(olf)-alpha) folding, thereby promoting-dependent cAMP accumulation in olfactory sensory neurons (By similarity). {ECO:0000250|UniProtKB:Q80XE1}. |
| Q9NYU2 | UGGT1 | Y1380 | Sugiyama | UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1) (hUGT1) (EC 2.4.1.-) (UDP--Glc:glycoprotein glucosyltransferase) (UDP-glucose ceramide glucosyltransferase-like 1) | Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic reticulum. Reglucosylated proteins are recognized by calreticulin for recycling to the endoplasmic reticulum and refolding or degradation. {ECO:0000269|PubMed:10694380}. |
| Q9UNM6 | PSMD13 | Y163 | Sugiyama | 26S proteasome non-ATPase regulatory subunit 13 (26S proteasome regulatory subunit RPN9) (26S proteasome regulatory subunit S11) (26S proteasome regulatory subunit p40.5) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}. |
| Q99640 | PKMYT1 | Y121 | Sugiyama | Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase (EC 2.7.11.1) (Myt1 kinase) | Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins (PubMed:10373560, PubMed:10504341, PubMed:9001210, PubMed:9268380). Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation (PubMed:9001210, PubMed:9268380). May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect (PubMed:9001210, PubMed:9268380). {ECO:0000269|PubMed:10373560, ECO:0000269|PubMed:10504341, ECO:0000269|PubMed:9001210, ECO:0000269|PubMed:9268380}. |
| Q14289 | PTK2B | Y46 | Sugiyama | Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) | Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. |
| Q15349 | RPS6KA2 | Y573 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q15375 | EPHA7 | Y754 | Sugiyama | Ephrin type-A receptor 7 (EC 2.7.10.1) (EPH homology kinase 3) (EHK-3) (EPH-like kinase 11) (EK11) (hEK11) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 and MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269|PubMed:17726105}. |
| O15230 | LAMA5 | Y448 | Sugiyama | Laminin subunit alpha-5 (Laminin-10 subunit alpha) (Laminin-11 subunit alpha) (Laminin-15 subunit alpha) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Plays a role in the regulation of skeletogenesis, through a mechanism that involves integrin-mediated signaling and PTK2B/PYK2 (PubMed:33242826). {ECO:0000269|PubMed:33242826}. |
| P00966 | ASS1 | Y190 | Sugiyama | Argininosuccinate synthase (EC 6.3.4.5) (Citrulline--aspartate ligase) | One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues. {ECO:0000305|PubMed:18473344, ECO:0000305|PubMed:27287393, ECO:0000305|PubMed:8792870}. |
| O75718 | CRTAP | Y206 | Sugiyama | Cartilage-associated protein | Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues. {ECO:0000269|PubMed:17055431}. |
| Q86V86 | PIM3 | Y201 | Sugiyama | Serine/threonine-protein kinase pim-3 (EC 2.7.11.1) | Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth. {ECO:0000269|PubMed:15540201, ECO:0000269|PubMed:16818649, ECO:0000269|PubMed:17270021, ECO:0000269|PubMed:17876606, ECO:0000269|PubMed:18593906}. |
| Q8N568 | DCLK2 | Y144 | 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}. |
| Q8TD08 | MAPK15 | Y335 | Sugiyama | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| Q9BZL6 | PRKD2 | Y728 | Sugiyama | Serine/threonine-protein kinase D2 (EC 2.7.11.13) (nPKC-D2) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}. |
| Q12841 | FSTL1 | Y240 | Sugiyama | Follistatin-related protein 1 (Follistatin-like protein 1) | Secreted glycoprotein that is involved in various physiological processes, such as angiogenesis, regulation of the immune response, cell proliferation and differentiation (PubMed:22265692, PubMed:29212066). Plays a role in the development of the central nervous system, skeletal system, lungs, and ureter (By similarity). Promotes endothelial cell survival, migration and differentiation into network structures in an AKT-dependent manner. Also promotes survival of cardiac myocytes (By similarity). Initiates various signaling cascades by activating different receptors on the cell surface such as DIP2A, TLR4 or BMP receptors (PubMed:20054002, PubMed:22265692). {ECO:0000250|UniProtKB:Q62356, ECO:0000269|PubMed:20054002, ECO:0000269|PubMed:22265692, ECO:0000269|PubMed:29212066}. |
| Q8WWX9 | SELENOM | Y89 | Sugiyama | Selenoprotein M (SelM) | May function as a thiol-disulfide oxidoreductase that participates in disulfide bond formation. {ECO:0000250}. |
| P04083 | ANXA1 | Y230 | Sugiyama | Annexin A1 (Annexin I) (Annexin-1) (Calpactin II) (Calpactin-2) (Chromobindin-9) (Lipocortin I) (Phospholipase A2 inhibitory protein) (p35) [Cleaved into: Annexin Ac2-26] | Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.; FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:25664854}. |
| O15198 | SMAD9 | Y92 | Sugiyama | Mothers against decapentaplegic homolog 9 (MAD homolog 9) (Mothers against DPP homolog 9) (Madh6) (SMAD family member 9) (SMAD 9) (Smad9) | Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor-regulated SMAD (R-SMAD). |
| Q15797 | SMAD1 | Y88 | Sugiyama | Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (JV4-1) (Mad-related protein 1) (SMAD family member 1) (SMAD 1) (Smad1) (hSMAD1) (Transforming growth factor-beta-signaling protein 1) (BSP-1) | Transcriptional modulator that plays a role in various cellular processes, including embryonic development, cell differentiation, and tissue homeostasis (PubMed:9335504). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form a heteromeric complex which translocates into the nucleus acting as transcription factor (PubMed:33667543). In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:33667543). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Positively regulates BMP4-induced expression of odontogenic development regulator MSX1 following IPO7-mediated nuclear import (By similarity). {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:33667543, ECO:0000269|PubMed:9335504}. |
| Q86WB0 | ZC3HC1 | Y105 | GPS6|ELM|iPTMNet|EPSD | Zinc finger C3HC-type protein 1 (Nuclear-interacting partner of ALK) (hNIPA) (Nuclear-interacting partner of anaplastic lymphoma kinase) | Required for proper positioning of a substantial amount of TPR at the nuclear basket (NB) through interaction with TPR. {ECO:0000269|PubMed:34440706}. |
| Q99717 | SMAD5 | Y89 | Sugiyama | Mothers against decapentaplegic homolog 5 (MAD homolog 5) (Mothers against DPP homolog 5) (JV5-1) (SMAD family member 5) (SMAD 5) (Smad5) (hSmad5) | Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form a heteromeric complex which translocates into the nucleus acting as transcription factor (PubMed:9442019). In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:33510867). Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes (PubMed:28675158). Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis (PubMed:28675158). {ECO:0000269|PubMed:12064918, ECO:0000269|PubMed:16516194, ECO:0000269|PubMed:28675158, ECO:0000269|PubMed:33510867, ECO:0000269|PubMed:9442019}. |
| Q9UM73 | ALK | Y1078 | Sugiyama | ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) | Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}. |
| A0A0G2JMM0 | LOC128966728 | T118 | ochoa | Uncharacterized protein | None |
| A2RU67 | FAM234B | T79 | ochoa | Protein FAM234B | None |
| A3KN83 | SBNO1 | T686 | ochoa | Protein strawberry notch homolog 1 (Monocyte protein 3) (MOP-3) | Plays a crucial role in the regulation of neural stem cells (NSCs) proliferation. Enhances the phosphorylation of GSK3B through the PI3K-Akt signaling pathway, thereby upregulating the Wnt/beta-catenin signaling pathway and promoting the proliferation of NSCs. Improves ischemic stroke recovery while inhibiting neuroinflammation through small extracellular vesicles (sEVs)-mediated mechanism. Enhances the secretion of sEVs from NSCs, which in turn inhibit both the MAPK and NF-kappaB pathways in microglia. This inhibition suppresses the pro-inflammatory M1 polarization of microglia, promoting a shift towards the M2 anti-inflammatory phenotype, which is beneficial for reducing neuroinflammation. {ECO:0000250|UniProtKB:Q689Z5}. |
| A6NES4 | MROH2A | T207 | ochoa | Maestro heat-like repeat-containing protein family member 2A (HEAT repeat-containing protein 7B1) | None |
| A8TX70 | COL6A5 | T870 | ochoa | Collagen alpha-5(VI) chain (Collagen alpha-1(XXIX) chain) (von Willebrand factor A domain-containing protein 4) | Collagen VI acts as a cell-binding protein. {ECO:0000250}. |
| K7ELQ4 | ATF7-NPFF | T204 | ochoa | ATF7-NPFF readthrough | None |
| M0QZ24 | None | T35 | ochoa | Glycosyl hydrolases family 38 C-terminal beta sandwich domain-containing protein | None |
| O00192 | ARVCF | T885 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00327 | BMAL1 | T224 | psp | Basic helix-loop-helix ARNT-like protein 1 (Aryl hydrocarbon receptor nuclear translocator-like protein 1) (Basic-helix-loop-helix-PAS protein MOP3) (Brain and muscle ARNT-like 1) (Class E basic helix-loop-helix protein 5) (bHLHe5) (Member of PAS protein 3) (PAS domain-containing protein 3) (bHLH-PAS protein JAP3) | Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504). Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (By similarity). Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B) (By similarity). {ECO:0000250|UniProtKB:Q9WTL8, ECO:0000269|PubMed:11441146, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:23955654, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}.; FUNCTION: (Microbial infection) Regulates SARS coronavirus-2/SARS-CoV-2 entry and replication in lung epithelial cells probably through the post-transcriptional regulation of ACE2 and interferon-stimulated gene expression. {ECO:0000269|PubMed:34545347}. |
| O00754 | MAN2B1 | T848 | ochoa | Lysosomal alpha-mannosidase (Laman) (EC 3.2.1.24) (Lysosomal acid alpha-mannosidase) (Mannosidase alpha class 2B member 1) (Mannosidase alpha-B) [Cleaved into: Lysosomal alpha-mannosidase A peptide; Lysosomal alpha-mannosidase B peptide; Lysosomal alpha-mannosidase C peptide; Lysosomal alpha-mannosidase D peptide; Lysosomal alpha-mannosidase E peptide] | Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages. |
| O14757 | CHEK1 | T378 | psp | Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.; FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. {ECO:0000269|PubMed:22184239}. |
| O15195 | VILL | T129 | ochoa | Villin-like protein | Possible tumor suppressor. |
| O15217 | GSTA4 | T193 | psp | Glutathione S-transferase A4 (EC 2.5.1.18) (GST class-alpha member 4) (Glutathione S-transferase A4-4) | Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE). {ECO:0000269|PubMed:10329152, ECO:0000269|PubMed:20085333}. |
| O15350 | TP73 | T27 | psp | Tumor protein p73 (p53-like transcription factor) (p53-related protein) | Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression (By similarity). It is an essential factor for the positive regulation of lung ciliated cell differentiation (PubMed:34077761). {ECO:0000250|UniProtKB:Q9JJP2, ECO:0000269|PubMed:10203277, ECO:0000269|PubMed:11753569, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:34077761}. |
| O15371 | EIF3D | T317 | ochoa | Eukaryotic translation initiation factor 3 subunit D (eIF3d) (Eukaryotic translation initiation factor 3 subunit 7) (eIF-3-zeta) (eIF3 p66) | mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815). {ECO:0000269|PubMed:18599441, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| O15403 | SLC16A6 | T231 | ochoa | Monocarboxylate transporter 7 (MCT 7) (Monocarboxylate transporter 6) (MCT 6) (Solute carrier family 16 member 6) | Monocarboxylate transporter selective for taurine. May associate with BSG/CD147 or EMB/GP70 ancillary proteins to mediate facilitative efflux or influx of taurine across the plasma membrane. The transport is pH- and sodium-independent. Rather low-affinity, is likely effective for taurine transport in tissues where taurine is present at high concentrations. {ECO:0000250|UniProtKB:Q7TMR7}. |
| O15439 | ABCC4 | T679 | ochoa | ATP-binding cassette sub-family C member 4 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (MRP/cMOAT-related ABC transporter) (Multi-specific organic anion transporter B) (MOAT-B) (Multidrug resistance-associated protein 4) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins (PubMed:11856762, PubMed:12523936, PubMed:12835412, PubMed:12883481, PubMed:15364914, PubMed:15454390, PubMed:16282361, PubMed:17959747, PubMed:18300232, PubMed:26721430). Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 (PubMed:17959747). Mediates the cotransport of bile acids with reduced glutathione (GSH) (PubMed:12523936, PubMed:12883481, PubMed:16282361). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (PubMed:11856762, PubMed:12105214, PubMed:15454390, PubMed:17344354, PubMed:18300232). Confers resistance to anticancer agents such as methotrexate (PubMed:11106685). {ECO:0000269|PubMed:11106685, ECO:0000269|PubMed:11856762, ECO:0000269|PubMed:12105214, ECO:0000269|PubMed:12523936, ECO:0000269|PubMed:12835412, ECO:0000269|PubMed:12883481, ECO:0000269|PubMed:15364914, ECO:0000269|PubMed:15454390, ECO:0000269|PubMed:16282361, ECO:0000269|PubMed:17344354, ECO:0000269|PubMed:17959747, ECO:0000269|PubMed:18300232, ECO:0000269|PubMed:26721430}. |
| O15503 | INSIG1 | T216 | psp | Insulin-induced gene 1 protein (INSIG-1) | Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12202038, PubMed:12535518, PubMed:16168377, PubMed:16399501, PubMed:16606821, PubMed:32322062). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:12202038, PubMed:16399501, PubMed:26311497, PubMed:32322062). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:32322062). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (PubMed:15899885, PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG1 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:26311497, PubMed:32322062). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligases AMFR/gp78 and/or RNF139 (PubMed:12535518, PubMed:16168377, PubMed:22143767). Also regulates degradation of SOAT2/ACAT2 when the lipid levels are low: initiates the ubiquitin-mediated degradation of SOAT2/ACAT2 via recruitment of the ubiquitin ligases AMFR/gp78 (PubMed:28604676). {ECO:0000269|PubMed:12202038, ECO:0000269|PubMed:12535518, ECO:0000269|PubMed:15899885, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:16606821, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:26311497, ECO:0000269|PubMed:28604676, ECO:0000269|PubMed:32322062}. |
| O43156 | TTI1 | T804 | ochoa | TELO2-interacting protein 1 homolog (Protein SMG10) | Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. {ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:36724785}. |
| O43167 | ZBTB24 | T126 | ochoa | Zinc finger and BTB domain-containing protein 24 (Zinc finger protein 450) | May be involved in BMP2-induced transcription. {ECO:0000250}. |
| O43255 | SIAH2 | T279 | psp | E3 ubiquitin-protein ligase SIAH2 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase SIAH2) (Seven in absentia homolog 2) (Siah-2) (hSiah2) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11483518, PubMed:19224863, PubMed:9334332). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11483518, PubMed:19224863, PubMed:9334332). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:11483518, PubMed:19224863, PubMed:9334332). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP) (PubMed:11483518, PubMed:19224863, PubMed:9334332). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia (PubMed:22878263). It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes (PubMed:11483518, PubMed:19224863, PubMed:22878263, PubMed:9334332). Has some overlapping function with SIAH1 (PubMed:11483518, PubMed:19224863, PubMed:9334332). Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not (PubMed:12411493). Promotes monoubiquitination of SNCA (PubMed:19224863). Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation (PubMed:26392558). Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance (PubMed:26392558). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1. {ECO:0000250|UniProtKB:Q06986, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:12411493, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:26392558, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:9334332}. |
| O43379 | WDR62 | T1265 | ochoa | WD repeat-containing protein 62 | Required for cerebral cortical development. Plays a role in neuronal proliferation and migration (PubMed:20729831, PubMed:20890278). Plays a role in mother-centriole-dependent centriole duplication; the function also seems to involve CEP152, CDK5RAP2 and CEP63 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). {ECO:0000269|PubMed:20729831, ECO:0000269|PubMed:20890278, ECO:0000269|PubMed:26297806}. |
| O43598 | DNPH1 | T51 | ochoa | 5-hydroxymethyl-dUMP N-hydrolase (EC 3.2.2.-) (2'-deoxynucleoside 5'-phosphate N-hydrolase 1) (c-Myc-responsive protein RCL) | Part of a nucleotide salvage pathway that eliminates epigenetically modified 5-hydroxymethyl-dCMP (hmdCMP) in a two-step process entailing deamination to cytotoxic 5-hydroxymethyl-dUMP (hmdUMP), followed by its hydrolysis into 5-hydroxymethyluracil (hmU) and 2-deoxy-D-ribose 5-phosphate (deoxyribosephosphate) (PubMed:33833118). Catalyzes the second step in that pathway, the hydrolysis of the N-glycosidic bond in hmdUMP, degrading this cytotoxic nucleotide to avoid its genomic integration (PubMed:33833118). {ECO:0000269|PubMed:33833118}. |
| O43683 | BUB1 | T173 | psp | Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) | Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}. |
| O43683 | BUB1 | T960 | psp | Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) | Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}. |
| O43824 | GTPBP6 | T315 | ochoa | Putative GTP-binding protein 6 (Pseudoautosomal GTP-binding protein-like) | None |
| O43918 | AIRE | T68 | psp | Autoimmune regulator (Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy protein) (APECED protein) | Transcription factor playing an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery, called tissue restricted antigens (TRA) (PubMed:26084028). Binds to G-doublets in an A/T-rich environment; the preferred motif is a tandem repeat of 5'-ATTGGTTA-3' combined with a 5'-TTATTA-3' box. Binds to nucleosomes (By similarity). Binds to chromatin and interacts selectively with histone H3 that is not methylated at 'Lys-4', not phosphorylated at 'Thr-3' and not methylated at 'Arg-2'. Functions as a sensor of histone H3 modifications that are important for the epigenetic regulation of gene expression. Mainly expressed by medullary thymic epithelial cells (mTECs), induces the expression of thousands of tissue-restricted proteins, which are presented on major histocompatibility complex class I (MHC-I) and MHC-II molecules to developing T-cells percolating through the thymic medulla (PubMed:26084028). Also induces self-tolerance through other mechanisms such as the regulation of the mTEC differentiation program. Controls the medullary accumulation of thymic dendritic cells and the development of regulatory T-cell through the regulation of XCL1 expression. Regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes. In thimic B-cells, allows the presentation of licensing-dependent endogenous self-anitgen for negative selection. In secondary lymphoid organs, induces functional inactivation of CD4(+) T-cells. Expressed by a distinct bone marrow-derived population, induces self-tolerance through a mechanism that does not require regulatory T-cells and is resitant to innate inflammatory stimuli (By similarity). {ECO:0000250|UniProtKB:Q9Z0E3, ECO:0000269|PubMed:11274163, ECO:0000269|PubMed:18292755, ECO:0000269|PubMed:26084028, ECO:0000305|PubMed:19302042, ECO:0000305|PubMed:26972725}. |
| O60216 | RAD21 | T188 | ochoa|psp | Double-strand-break repair protein rad21 homolog (hHR21) (Nuclear matrix protein 1) (NXP-1) (SCC1 homolog) [Cleaved into: 64-kDa C-terminal product (64-kDa carboxy-terminal product) (65-kDa carboxy-terminal product)] | [Double-strand-break repair protein rad21 homolog]: As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions (PubMed:11509732). The cohesin complex may also play a role in spindle pole assembly during mitosis (PubMed:11590136). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (By similarity). May control RUNX1 gene expression (Probable). Binds to and represses APOB gene promoter (PubMed:25575569). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity). {ECO:0000250|UniProtKB:Q61550, ECO:0000250|UniProtKB:Q6TEL1, ECO:0000269|PubMed:11509732, ECO:0000269|PubMed:11590136, ECO:0000269|PubMed:25575569, ECO:0000305|PubMed:25575569}.; FUNCTION: [64-kDa C-terminal product]: May promote apoptosis. {ECO:0000269|PubMed:11875078, ECO:0000269|PubMed:12417729}. |
| O60271 | SPAG9 | T418 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60281 | ZNF292 | T833 | ochoa | Zinc finger protein 292 | May be involved in transcriptional regulation. |
| O60566 | BUB1B | T563 | ochoa | Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (EC 2.7.11.1) (MAD3/BUB1-related protein kinase) (hBUBR1) (Mitotic checkpoint kinase MAD3L) (Protein SSK1) | Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression. {ECO:0000269|PubMed:10477750, ECO:0000269|PubMed:11702782, ECO:0000269|PubMed:14706340, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:19411850, ECO:0000269|PubMed:19503101}. |
| O60610 | DIAPH1 | T1238 | psp | Protein diaphanous homolog 1 (Diaphanous-related formin-1) (DRF1) | Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (By similarity). {ECO:0000250|UniProtKB:O08808, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24781755, ECO:0000269|PubMed:26912466}. |
| O60664 | PLIN3 | T191 | ochoa | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| O60664 | PLIN3 | T216 | ochoa | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| O75167 | PHACTR2 | T564 | ochoa | Phosphatase and actin regulator 2 | None |
| O75396 | SEC22B | T140 | ochoa | Vesicle-trafficking protein SEC22b (ER-Golgi SNARE of 24 kDa) (ERS-24) (ERS24) (SEC22 vesicle-trafficking protein homolog B) (SEC22 vesicle-trafficking protein-like 1) | SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER. {ECO:0000269|PubMed:15272311}. |
| O75436 | VPS26A | T307 | ochoa | Vacuolar protein sorting-associated protein 26A (Vesicle protein sorting 26A) (hVPS26) | Acts as a component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins (Probable). The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:15078902, PubMed:15078903). Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922). Required for the endosomal localization of WASHC2A (indicative for the WASH complex) (PubMed:22070227). Required for the endosomal localization of TBC1D5 (PubMed:20923837). Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (PubMed:22279231). Involved in retromer-independent lysosomal sorting of F2R (PubMed:16407403). Involved in recycling of ADRB2 (PubMed:21602791). Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity). {ECO:0000250|UniProtKB:P40336, ECO:0000269|PubMed:15078902, ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:15247922, ECO:0000269|PubMed:16407403, ECO:0000269|PubMed:22070227, ECO:0000269|PubMed:22279231, ECO:0000303|PubMed:20923837, ECO:0000303|PubMed:21602791, ECO:0000303|PubMed:21725319, ECO:0000303|PubMed:23563491, ECO:0000305}. |
| O75674 | TOM1L1 | T455 | ochoa | TOM1-like protein 1 (Src-activating and signaling molecule protein) (Target of Myb-like protein 1) | Probable adapter protein involved in signaling pathways. Interacts with the SH2 and SH3 domains of various signaling proteins when it is phosphorylated. May promote FYN activation, possibly by disrupting intramolecular SH3-dependent interactions (By similarity). {ECO:0000250}. |
| O94762 | RECQL5 | T950 | ochoa | ATP-dependent DNA helicase Q5 (EC 5.6.2.4) (DNA 3'-5' helicase RecQ5) (DNA helicase, RecQ-like type 5) (RecQ5) (RecQ protein-like 5) | DNA helicase that plays an important role in DNA replication, transcription and repair (PubMed:20643585, PubMed:22973052, PubMed:28100692). Probably unwinds DNA in a 3'-5' direction (Probable) (PubMed:28100692). Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability (PubMed:20231364). Also associates with POLR1A and enforces the stability of ribosomal DNA arrays (PubMed:27502483). Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress (PubMed:22013166). Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis (PubMed:28575661). Required for efficient DNA repair, including repair of inter-strand cross-links (PubMed:23715498). Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination. A core helicase fragment (residues 11-609) binds preferentially to splayed duplex, looped and ssDNA (PubMed:28100692). {ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20643585, ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22973052, ECO:0000269|PubMed:23715498, ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:27502483, ECO:0000269|PubMed:28100692, ECO:0000269|PubMed:28575661, ECO:0000305|PubMed:28100692}. |
| O94856 | NFASC | T1283 | ochoa | Neurofascin | Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions. {ECO:0000250}. |
| O94874 | UFL1 | T412 | ochoa | E3 UFM1-protein ligase 1 (EC 2.3.2.-) (E3 UFM1-protein transferase 1) (Multiple alpha-helix protein located at ER) (Novel LZAP-binding protein) (Regulator of C53/LZAP and DDRGK1) | E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:27351204, PubMed:30626644, PubMed:30783677, PubMed:32160526, PubMed:32807901, PubMed:35394863, PubMed:36121123, PubMed:36543799, PubMed:36893266, PubMed:37036982, PubMed:37311461, PubMed:37595036, PubMed:37795761, PubMed:38377992, PubMed:38383785, PubMed:38383789). Catalyzes ufmylation of many protein, such as CD274/PD-L1, CDK5RAP3, CYB5R3, DDRGK1, EIF6, histone H4, MRE11, P4HB, PDCD1/PD-1, TRIP4, RPN1, RPS20/uS10, RPL10/uL16, RPL26/uL24, SYVN1/HRD1 and TP53/p53 (PubMed:20018847, PubMed:20531390, PubMed:25219498, PubMed:30783677, PubMed:30886146, PubMed:32160526, PubMed:35753586, PubMed:36543799, PubMed:36893266, PubMed:37036982, PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). As part of the UREL complex, plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 occurs on free 60S ribosomes following ribosome dissociation: it weakens the junction between post-termination 60S subunits and SEC61 translocons, promoting release and recycling of the large ribosomal subunit from the endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either take place after normal termination of translation or after ribosome stalling during cotranslational translocation at the endoplasmic reticulum (PubMed:37036982, PubMed:37595036, PubMed:38383785, PubMed:38383789). Involved in reticulophagy in response to endoplasmic reticulum stress by mediating ufmylation of proteins such as CYB5R3 and RPN1, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:23152784, PubMed:32160526, PubMed:36543799). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:32050156). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is, a collateral effect or is required for ufmylation (PubMed:20018847, PubMed:20531390). Acts as a negative regulator of T-cell activation by mediating ufmylation and stabilization of PDCD1/PD-1 (PubMed:38377992). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 and ufmylation of MRE11 (PubMed:30783677, PubMed:30886146). Mediates ufmylation of TP53/p53, promoting its stability (PubMed:32807901). Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (PubMed:25219498). Required for hematopoietic stem cell function and hematopoiesis (By similarity). {ECO:0000250|UniProtKB:Q8CCJ3, ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180, ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:20531390, ECO:0000269|PubMed:23152784, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:27351204, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:30783677, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:32050156, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:32807901, ECO:0000269|PubMed:35394863, ECO:0000269|PubMed:35753586, ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:36893266, ECO:0000269|PubMed:37036982, ECO:0000269|PubMed:37311461, ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:37795761, ECO:0000269|PubMed:38377992, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}. |
| O94886 | TMEM63A | T765 | ochoa | Mechanosensitive cation channel TMEM63A (Transmembrane protein 63A) (hTMEM63A) | Mechanosensitive cation channel with low conductance and high activation threshold (PubMed:30382938, PubMed:31587869, PubMed:37543036). In contrast to TMEM63B, does not show phospholipid scramblase activity (PubMed:39716028). Acts as a regulator of lysosomal morphology by mediating lysosomal mechanosensitivity (By similarity). Important for the baby's first breath and respiration throughout life (PubMed:38127458). Upon lung inflation conducts cation currents in alveolar type 1 and 2 cells triggering lamellar body exocytosis and surfactant secretion into airspace (PubMed:38127458). Also acts as an osmosensitive cation channel preferentially activated by hypotonic stress (By similarity). {ECO:0000250|UniProtKB:Q91YT8, ECO:0000269|PubMed:30382938, ECO:0000269|PubMed:31587869, ECO:0000269|PubMed:37543036, ECO:0000269|PubMed:38127458, ECO:0000269|PubMed:39716028}. |
| O95436 | SLC34A2 | T56 | ochoa | Sodium-dependent phosphate transport protein 2B (Sodium-phosphate transport protein 2B) (Na(+)-dependent phosphate cotransporter 2B) (NaPi3b) (Sodium/phosphate cotransporter 2B) (Na(+)/Pi cotransporter 2B) (NaPi-2b) (Solute carrier family 34 member 2) | Involved in actively transporting phosphate into cells via Na(+) cotransport. {ECO:0000269|PubMed:10329428}. |
| O95551 | TDP2 | T92 | ochoa|psp | Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (hTDP2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (ETS1-associated protein 2) (ETS1-associated protein II) (EAPII) (TRAF and TNF receptor-associated protein) (Tyrosyl-RNA phosphodiesterase) (VPg unlinkase) | DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (PubMed:27060144, PubMed:27099339). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. Also has 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. {ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:21030584, ECO:0000269|PubMed:21921940, ECO:0000269|PubMed:21980489, ECO:0000269|PubMed:22405347, ECO:0000269|PubMed:22822062, ECO:0000269|PubMed:24658003, ECO:0000269|PubMed:27060144, ECO:0000269|PubMed:27099339}.; FUNCTION: (Microbial infection) Used by picornaviruses to remove the small polypeptide, VPg (virus Protein genome-linked, the primer for viral RNA synthesis), from the genomic RNA of the virus. Acts as a 5'-tyrosyl RNA phosphodiesterase and cleaves the covalent VPg-Tyr-RNA bond. This cleavage would play a role in viral replication and occur in viral replication vesicles, but would not act on viral mRNA. {ECO:0000269|PubMed:22908287, ECO:0000269|PubMed:32023921}. |
| P01106 | MYC | T23 | psp | Myc proto-oncogene protein (Class E basic helix-loop-helix protein 39) (bHLHe39) (Proto-oncogene c-Myc) (Transcription factor p64) | Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of growth-related genes (PubMed:24940000, PubMed:25956029). Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000, PubMed:25956029). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells (By similarity). Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). {ECO:0000250|UniProtKB:P01108, ECO:0000269|PubMed:20010808, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25956029}. |
| P02686 | MBP | T154 | ochoa | Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) | The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}. |
| P03372 | ESR1 | T311 | psp | Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) | Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [Isoform 3]: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}. |
| P04049 | RAF1 | T481 | psp | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. |
| P04049 | RAF1 | T543 | psp | RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) | Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}. |
| P04075 | ALDOA | T49 | ochoa | Fructose-bisphosphate aldolase A (EC 4.1.2.13) (Lung cancer antigen NY-LU-1) (Muscle-type aldolase) | Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also function as scaffolding protein (By similarity). {ECO:0000250, ECO:0000269|PubMed:14766013}. |
| P04083 | ANXA1 | T101 | ochoa | Annexin A1 (Annexin I) (Annexin-1) (Calpactin II) (Calpactin-2) (Chromobindin-9) (Lipocortin I) (Phospholipase A2 inhibitory protein) (p35) [Cleaved into: Annexin Ac2-26] | Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.; FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:25664854}. |
| P04637 | TP53 | T211 | psp | Cellular tumor antigen p53 (Antigen NY-CO-13) (Phosphoprotein p53) (Tumor suppressor p53) | Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:35618207, PubMed:36634798, PubMed:38653238, PubMed:9840937). Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:38653238, PubMed:9840937). Negatively regulates cell division by controlling expression of a set of genes required for this process (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed:12524540, PubMed:17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17189187, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:24652652, ECO:0000269|PubMed:35618207, ECO:0000269|PubMed:36634798, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:9840937}. |
| P05090 | APOD | T168 | ochoa | Apolipoprotein D (Apo-D) (ApoD) | APOD occurs in the macromolecular complex with lecithin-cholesterol acyltransferase. It is probably involved in the transport and binding of bilin. Appears to be able to transport a variety of ligands in a number of different contexts. |
| P05181 | CYP2E1 | T373 | psp | Cytochrome P450 2E1 (EC 1.14.14.1) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) | A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}. |
| P05181 | CYP2E1 | T387 | psp | Cytochrome P450 2E1 (EC 1.14.14.1) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) | A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}. |
| P05976 | MYL1 | T65 | ochoa | Myosin light chain 1/3, skeletal muscle isoform (MLC1/MLC3) (MLC1F/MLC3F) (Myosin light chain alkali 1/2) (Myosin light chain A1/A2) | Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function. {ECO:0000269|PubMed:30215711}. |
| P05976 | MYL1 | T84 | ochoa | Myosin light chain 1/3, skeletal muscle isoform (MLC1/MLC3) (MLC1F/MLC3F) (Myosin light chain alkali 1/2) (Myosin light chain A1/A2) | Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function. {ECO:0000269|PubMed:30215711}. |
| P05976 | MYL1 | T87 | ochoa | Myosin light chain 1/3, skeletal muscle isoform (MLC1/MLC3) (MLC1F/MLC3F) (Myosin light chain alkali 1/2) (Myosin light chain A1/A2) | Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function. {ECO:0000269|PubMed:30215711}. |
| P06239 | LCK | T210 | ochoa | Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) | Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}. |
| P06400 | RB1 | T601 | ochoa | Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110) | Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; FUNCTION: (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}. |
| P07451 | CA3 | T216 | ochoa | Carbonic anhydrase 3 (EC 4.2.1.1) (Carbonate dehydratase III) (Carbonic anhydrase III) (CA-III) | Reversible hydration of carbon dioxide. {ECO:0000269|PubMed:17427958, ECO:0000269|PubMed:18618712}. |
| P07814 | EPRS1 | T467 | ochoa | Bifunctional glutamate/proline--tRNA ligase (Bifunctional aminoacyl-tRNA synthetase) (Cell proliferation-inducing gene 32 protein) (Glutamatyl-prolyl-tRNA synthetase) [Includes: Glutamate--tRNA ligase (EC 6.1.1.17) (Glutamyl-tRNA synthetase) (GluRS); Proline--tRNA ligase (EC 6.1.1.15) (Prolyl-tRNA synthetase)] | Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (PubMed:23263184, PubMed:24100331, PubMed:29576217, PubMed:3290852, PubMed:37212275). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3'-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts (PubMed:15479637, PubMed:23071094). Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:28178239, ECO:0000269|PubMed:29576217, ECO:0000269|PubMed:3290852, ECO:0000269|PubMed:37212275}. |
| P08133 | ANXA6 | T535 | ochoa | Annexin A6 (67 kDa calelectrin) (Annexin VI) (Annexin-6) (Calphobindin-II) (CPB-II) (Chromobindin-20) (Lipocortin VI) (Protein III) (p68) (p70) | May associate with CD21. May regulate the release of Ca(2+) from intracellular stores. |
| P08238 | HSP90AB1 | T89 | psp | Heat shock protein HSP 90-beta (HSP 90) (Heat shock 84 kDa) (HSP 84) (HSP84) (Heat shock protein family C member 3) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Binding to N.meningitidis NadA stimulates monocytes (PubMed:21949862). Seems to interfere with N.meningitidis NadA-mediated invasion of human cells (Probable). {ECO:0000269|PubMed:21949862, ECO:0000305|PubMed:22066472}. |
| P08590 | MYL3 | T165 | ochoa | Myosin light chain 3 (Cardiac myosin light chain 1) (CMLC1) (Myosin light chain 1, slow-twitch muscle B/ventricular isoform) (MLC1SB) (Ventricular myosin alkali light chain) (Ventricular myosin light chain 1) (VLCl) (Ventricular/slow twitch myosin alkali light chain) (MLC-lV/sb) | Regulatory light chain of myosin. Does not bind calcium. |
| P08670 | VIM | T436 | ochoa | Vimentin | Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally. Plays a role in cell directional movement, orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Protects SCRIB from proteasomal degradation and facilitates its localization to intermediate filaments in a cell contact-mediated manner (By similarity). {ECO:0000250|UniProtKB:A0A8C0N8E3, ECO:0000250|UniProtKB:P31000}.; FUNCTION: Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. {ECO:0000269|PubMed:21746880}. |
| P09327 | VIL1 | T363 | ochoa | Villin-1 | Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. {ECO:0000269|PubMed:11500485, ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600, ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613, ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174, ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}. |
| P09874 | PARP1 | T420 | ochoa | Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] | Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}. |
| P0CG47 | UBB | T55 | ochoa | Polyubiquitin-B [Cleaved into: Ubiquitin] | [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. {ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:34239127, ECO:0000303|PubMed:19754430}. |
| P0CG48 | UBC | T55 | ochoa | Polyubiquitin-C [Cleaved into: Ubiquitin] | [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. During ubiquitination, the acceptor ubiquitin is positioned in the active site via direct interaction with the E2 ubiquitin-conjugating enzymes such as UBE2R2 (PubMed:38326650). As a monoubiquitin, its C-terminal glycine is recognized as a C-degron by Cul2-RING (CRL2) E3 ubiquitin-protein ligase complexes (PubMed:39548056). {ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:34239127, ECO:0000269|PubMed:38326650, ECO:0000269|PubMed:39548056, ECO:0000303|PubMed:19754430}. |
| P10114 | RAP2A | T61 | ochoa | Ras-related protein Rap-2a (EC 3.6.5.2) (RbBP-30) | Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form (PubMed:14966141, PubMed:15342639, PubMed:16246175, PubMed:16540189, PubMed:18930710, PubMed:20159449, PubMed:35293963). In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK (PubMed:14966141, PubMed:15342639, PubMed:18930710, PubMed:20159449). Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development (PubMed:20159449). More generally, it is part of several signaling cascades and regulates cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading (PubMed:14966141, PubMed:15342639, PubMed:16246175, PubMed:16540189, PubMed:18930710, PubMed:20159449, PubMed:35293963). {ECO:0000269|PubMed:14966141, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:16246175, ECO:0000269|PubMed:16540189, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:35293963}. |
| P10398 | ARAF | T455 | ochoa | Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks) | Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789). {ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:36402789}.; FUNCTION: [Isoform 2]: Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. {ECO:0000269|PubMed:22609986}. |
| P10746 | UROS | T242 | ochoa | Uroporphyrinogen-III synthase (UROIIIS) (UROS) (EC 4.2.1.75) (Hydroxymethylbilane hydrolyase [cyclizing]) (Uroporphyrinogen-III cosynthase) | Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins (PubMed:11689424, PubMed:18004775). Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme) (PubMed:11689424, PubMed:18004775). {ECO:0000269|PubMed:11689424, ECO:0000269|PubMed:18004775}. |
| P10809 | HSPD1 | T409 | ochoa | 60 kDa heat shock protein, mitochondrial (EC 5.6.1.7) (60 kDa chaperonin) (Chaperonin 60) (CPN60) (Heat shock protein 60) (HSP-60) (Hsp60) (Heat shock protein family D member 1) (HuCHA60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) | Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:11422376, PubMed:1346131). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}. |
| P11137 | MAP2 | T522 | ochoa | Microtubule-associated protein 2 (MAP-2) | The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules. |
| P11142 | HSPA8 | T418 | ochoa | Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Heat shock protein family A member 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity). {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. |
| P11413 | G6PD | T145 | psp | Glucose-6-phosphate 1-dehydrogenase (G6PD) (EC 1.1.1.49) | Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:35122041, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:743300}. |
| P11498 | PC | T19 | ochoa | Pyruvate carboxylase, mitochondrial (EC 6.4.1.1) (Pyruvic carboxylase) (PCB) | Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate. {ECO:0000269|PubMed:9585002}. |
| P11498 | PC | T1035 | ochoa | Pyruvate carboxylase, mitochondrial (EC 6.4.1.1) (Pyruvic carboxylase) (PCB) | Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate. {ECO:0000269|PubMed:9585002}. |
| P12882 | MYH1 | T1070 | ochoa | Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) | Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}. |
| P12882 | MYH1 | T1300 | ochoa | Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) | Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}. |
| P12882 | MYH1 | T1725 | ochoa | Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) | Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}. |
| P13535 | MYH8 | T1724 | ochoa | Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) | Muscle contraction. |
| P13929 | ENO3 | T229 | ochoa | Beta-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (Enolase 3) (Muscle-specific enolase) (MSE) (Skeletal muscle enolase) | Glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Appears to have a function in striated muscle development and regeneration. {ECO:0000250|UniProtKB:P15429}. |
| P14317 | HCLS1 | T333 | ochoa | Hematopoietic lineage cell-specific protein (Hematopoietic cell-specific LYN substrate 1) (LckBP1) (p75) | Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression. |
| P14649 | MYL6B | T101 | ochoa | Myosin light chain 6B (Myosin light chain 1 slow-twitch muscle A isoform) (MLC1sa) (Smooth muscle and nonmuscle myosin light chain alkali 6B) | Regulatory light chain of myosin. Does not bind calcium. |
| P15311 | EZR | T98 | ochoa | Ezrin (Cytovillin) (Villin-2) (p81) | Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}. |
| P15924 | DSP | T2524 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P16144 | ITGB4 | T1463 | ochoa | Integrin beta-4 (GP150) (CD antigen CD104) | Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}. |
| P16157 | ANK1 | T1625 | ochoa | Ankyrin-1 (ANK-1) (Ankyrin-R) (Erythrocyte ankyrin) | Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions. {ECO:0000269|PubMed:12456646, ECO:0000269|PubMed:35835865}.; FUNCTION: [Isoform Mu17]: Together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils. {ECO:0000269|PubMed:12527750}. |
| P16284 | PECAM1 | T709 | ochoa | Platelet endothelial cell adhesion molecule (PECAM-1) (EndoCAM) (GPIIA') (PECA1) (CD antigen CD31) | Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes (PubMed:19342684). Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions (PubMed:27958302). Heterophilic interaction with CD177 plays a role in transendothelial migration of neutrophils (PubMed:17580308). Homophilic ligation of PECAM1 prevents macrophage-mediated phagocytosis of neighboring viable leukocytes by transmitting a detachment signal (PubMed:12110892). Promotes macrophage-mediated phagocytosis of apoptotic leukocytes by tethering them to the phagocytic cells; PECAM1-mediated detachment signal appears to be disabled in apoptotic leukocytes (PubMed:12110892). Modulates bradykinin receptor BDKRB2 activation (PubMed:18672896). Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in endothelial cells (PubMed:18672896). Induces susceptibility to atherosclerosis (By similarity). {ECO:0000250|UniProtKB:Q08481, ECO:0000269|PubMed:12110892, ECO:0000269|PubMed:17580308, ECO:0000269|PubMed:18672896, ECO:0000269|PubMed:19342684, ECO:0000269|PubMed:27958302}.; FUNCTION: [Isoform Delta15]: Does not protect against apoptosis. {ECO:0000269|PubMed:18388311}. |
| P16885 | PLCG2 | T1219 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-gamma-2) (Phospholipase C-IV) (PLC-IV) (Phospholipase C-gamma-2) (PLC-gamma-2) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. {ECO:0000269|PubMed:23000145}. |
| P16989 | YBX3 | T20 | 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}. |
| P17812 | CTPS1 | T455 | psp | CTP synthase 1 (EC 6.3.4.2) (CTP synthetase 1) (UTP--ammonia ligase 1) | This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity. {ECO:0000269|PubMed:16179339, ECO:0000269|PubMed:24870241}. |
| P18206 | VCL | T614 | 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 | T754 | 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}. |
| P18433 | PTPRA | T197 | ochoa | Receptor-type tyrosine-protein phosphatase alpha (Protein-tyrosine phosphatase alpha) (R-PTP-alpha) (EC 3.1.3.48) | Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation (By similarity). Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42 (By similarity). {ECO:0000250|UniProtKB:P18052}. |
| P19338 | NCL | T405 | ochoa | Nucleolin (Protein C23) | Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}. |
| P19338 | NCL | T498 | ochoa | Nucleolin (Protein C23) | Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}. |
| P19338 | NCL | T584 | ochoa | Nucleolin (Protein C23) | Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. {ECO:0000269|PubMed:10393184}. |
| P20839 | IMPDH1 | T159 | ochoa | Inosine-5'-monophosphate dehydrogenase 1 (IMP dehydrogenase 1) (IMPD 1) (IMPDH 1) (EC 1.1.1.205) (IMPDH-I) | Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors. |
| P20929 | NEB | T1517 | ochoa | Nebulin | This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin. |
| P21333 | FLNA | T2062 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21462 | FPR1 | T329 | psp | fMet-Leu-Phe receptor (fMLP receptor) (N-formyl peptide receptor) (FPR) (N-formylpeptide chemoattractant receptor) | High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors (PubMed:10514456, PubMed:15153520, PubMed:2161213, PubMed:2176894). Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release (PubMed:15153520, PubMed:15210802, PubMed:1712023, PubMed:2161213). This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system (PubMed:10514456, PubMed:1712023). Receptor for TAFA4, mediates its effects on chemoattracting macrophages, promoting phagocytosis and increasing ROS release (PubMed:25109685). Receptor for cathepsin CTSG, leading to increased phagocyte chemotaxis (PubMed:15210802). {ECO:0000269|PubMed:10514456, ECO:0000269|PubMed:15153520, ECO:0000269|PubMed:2161213, ECO:0000269|PubMed:2176894, ECO:0000269|PubMed:25109685, ECO:0000303|PubMed:10514456, ECO:0000303|PubMed:1712023, ECO:0000303|PubMed:2161213, ECO:0000303|PubMed:2176894}. |
| P21964 | COMT | T81 | ochoa | Catechol O-methyltransferase (EC 2.1.1.6) | Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol. {ECO:0000269|PubMed:11559542, ECO:0000269|PubMed:21846718}. |
| P22314 | UBA1 | T682 | ochoa | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
| P23975 | SLC6A2 | T30 | psp | Sodium-dependent noradrenaline transporter (Norepinephrine transporter) (NET) (Solute carrier family 6 member 2) | Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921, PubMed:39395208, PubMed:39048818). {ECO:0000250|UniProtKB:O55192, ECO:0000269|PubMed:11093780, ECO:0000269|PubMed:2008212, ECO:0000269|PubMed:38750358, ECO:0000269|PubMed:39048818, ECO:0000269|PubMed:8125921}. |
| P26038 | MSN | T66 | psp | Moesin (Membrane-organizing extension spike protein) | Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (PubMed:10212266). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (PubMed:12387735, PubMed:15039356). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:9298994, PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By similarity). Also participates in immunologic synapse formation (PubMed:27405666). {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:10212266, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:27405666, ECO:0000269|PubMed:9298994, ECO:0000269|PubMed:9616160}. |
| P26639 | TARS1 | T450 | ochoa | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P26639 | TARS1 | T657 | ochoa | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P27708 | CAD | T1914 | ochoa | Multifunctional protein CAD (Carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase) [Includes: Glutamine-dependent carbamoyl phosphate synthase (EC 6.3.5.5); Glutamine amidotransferase (GATase) (GLNase) (EC 3.5.1.2); Ammonium-dependent carbamoyl phosphate synthase (CPS) (CPSase) (EC 6.3.4.16); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] | Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000269|PubMed:24332717}. |
| P27986 | PIK3R1 | T603 | ochoa | Phosphatidylinositol 3-kinase regulatory subunit alpha (PI3-kinase regulatory subunit alpha) (PI3K regulatory subunit alpha) (PtdIns-3-kinase regulatory subunit alpha) (Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha) (PI3-kinase subunit p85-alpha) (PtdIns-3-kinase regulatory subunit p85-alpha) | Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (PubMed:17626883, PubMed:19805105, PubMed:7518429). Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348923). {ECO:0000269|PubMed:17626883, ECO:0000269|PubMed:19805105, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:7518429}. |
| P29317 | EPHA2 | T587 | ochoa | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P29320 | EPHA3 | T595 | ochoa | Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}. |
| P29323 | EPHB2 | T959 | ochoa | Ephrin type-B receptor 2 (EC 2.7.10.1) (Developmentally-regulated Eph-related tyrosine kinase) (ELK-related tyrosine kinase) (EPH tyrosine kinase 3) (EPH-like kinase 5) (EK5) (hEK5) (Renal carcinoma antigen NY-REN-47) (Tyrosine-protein kinase TYRO5) (Tyrosine-protein kinase receptor EPH-3) [Cleaved into: EphB2/CTF1; EphB2/CTF2] | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874). {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:30213874}. |
| P30086 | PEBP1 | T42 | ochoa|psp | Phosphatidylethanolamine-binding protein 1 (PEBP-1) (HCNPpp) (Neuropolypeptide h3) (Prostatic-binding protein) (Raf kinase inhibitor protein) (RKIP) [Cleaved into: Hippocampal cholinergic neurostimulating peptide (HCNP)] | Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation. {ECO:0000250, ECO:0000269|PubMed:18294816}.; FUNCTION: HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity). {ECO:0000250}. |
| P30307 | CDC25C | T261 | ochoa | M-phase inducer phosphatase 3 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25C) | Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle (PubMed:8119945). When phosphorylated, highly effective in activating G2 cells into prophase (PubMed:8119945). Directly dephosphorylates CDK1 and activates its kinase activity (PubMed:8119945). {ECO:0000269|PubMed:8119945}. |
| P30411 | BDKRB2 | T162 | psp | B2 bradykinin receptor (B2R) (BK-2 receptor) | Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:1314587, ECO:0000269|PubMed:1329734}. |
| P31749 | AKT1 | T443 | ochoa | RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha) | AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:15526160, PubMed:15861136, PubMed:21432781, PubMed:21620960, PubMed:31204173). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960, PubMed:29343641, PubMed:31204173). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF1 (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (PubMed:30504268). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (PubMed:15861136). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (PubMed:31204173). {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10358075, ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941, ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:18507042, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20471940, ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:30504268, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058, ECO:0000269|PubMed:9829964, ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}. |
| P31942 | HNRNPH3 | T207 | ochoa | Heterogeneous nuclear ribonucleoprotein H3 (hnRNP H3) (Heterogeneous nuclear ribonucleoprotein 2H9) (hnRNP 2H9) | Involved in the splicing process and participates in early heat shock-induced splicing arrest. Due to their great structural variations the different isoforms may possess different functions in the splicing reaction. |
| P31943 | HNRNPH1 | T301 | ochoa | Heterogeneous nuclear ribonucleoprotein H (hnRNP H) [Cleaved into: Heterogeneous nuclear ribonucleoprotein H, N-terminally processed] | This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG). {ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:16946708}. |
| P32780 | GTF2H1 | T74 | psp | General transcription factor IIH subunit 1 (Basic transcription factor 2 62 kDa subunit) (BTF2 p62) (General transcription factor IIH polypeptide 1) (TFIIH basal transcription factor complex p62 subunit) | Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:9852112}. |
| P33240 | CSTF2 | T106 | ochoa | Cleavage stimulation factor subunit 2 (CF-1 64 kDa subunit) (Cleavage stimulation factor 64 kDa subunit) (CSTF 64 kDa subunit) (CstF-64) | One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs. {ECO:0000269|PubMed:32816001, ECO:0000269|PubMed:9199325}. |
| P33527 | ABCC1 | T249 | psp | Multidrug resistance-associated protein 1 (EC 7.6.2.2) (ATP-binding cassette sub-family C member 1) (Glutathione-S-conjugate-translocating ATPase ABCC1) (EC 7.6.2.3) (Leukotriene C(4) transporter) (LTC4 transporter) | Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769). Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity). Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells (PubMed:9426231). {ECO:0000250|UniProtKB:O35379, ECO:0000269|PubMed:10064732, ECO:0000269|PubMed:11114332, ECO:0000269|PubMed:16230346, ECO:0000269|PubMed:17050692, ECO:0000269|PubMed:36070769, ECO:0000269|PubMed:7961706, ECO:0000269|PubMed:9281595, ECO:0000269|PubMed:9426231}. |
| P35222 | CTNNB1 | T371 | psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35222 | CTNNB1 | T393 | psp | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35222 | CTNNB1 | T679 | ochoa | Catenin beta-1 (Beta-catenin) | Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). Also acts as a coactivator for other transcription factors, such as NR5A2 (PubMed:22187462). Promotes epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via driving transcription of CTNNB1/TCF-target genes (PubMed:29910125). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion (PubMed:18086858). Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization (PubMed:21262353). Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (PubMed:18957423). Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (PubMed:22155184). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (By similarity). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (By similarity). {ECO:0000250|UniProtKB:Q02248, ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18957423, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22187462, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:29910125}. |
| P35232 | PHB1 | T108 | psp | Prohibitin 1 | Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus (PubMed:11302691, PubMed:20959514, PubMed:28017329, PubMed:31522117). Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner (By similarity). Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells (By similarity). {ECO:0000250|UniProtKB:P67778, ECO:0000250|UniProtKB:P67779, ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:20959514, ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117}.; FUNCTION: In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (By similarity). Regulates mitochondrial respiration activity playing a role in cellular aging (PubMed:11302691). The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117). {ECO:0000250|UniProtKB:P67778, ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117, ECO:0000305}.; FUNCTION: In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses (PubMed:14500729). Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells (PubMed:31899195). {ECO:0000269|PubMed:14500729, ECO:0000269|PubMed:31899195}.; FUNCTION: In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates (By similarity). Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity). {ECO:0000250|UniProtKB:P67778}. |
| P35408 | PTGER4 | T428 | ochoa | Prostaglandin E2 receptor EP4 subtype (PGE receptor EP4 subtype) (PGE2 receptor EP4 subtype) (Prostanoid EP4 receptor) | Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function. |
| P35548 | MSX2 | T141 | psp | Homeobox protein MSX-2 (Homeobox protein Hox-8) | Acts as a transcriptional regulator in bone development. Represses the ALPL promoter activity and antagonizes the stimulatory effect of DLX5 on ALPL expression during osteoblast differentiation. Probable morphogenetic role. May play a role in limb-pattern formation. In osteoblasts, suppresses transcription driven by the osteocalcin FGF response element (OCFRE). Binds to the homeodomain-response element of the ALPL promoter. {ECO:0000269|PubMed:12145306}. |
| P35579 | MYH9 | T383 | ochoa | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P35749 | MYH11 | T604 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P40926 | MDH2 | T54 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P40926 | MDH2 | T73 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P42345 | MTOR | T308 | psp | Serine/threonine-protein kinase mTOR (EC 2.7.11.1) (FK506-binding protein 12-rapamycin complex-associated protein 1) (FKBP12-rapamycin complex-associated protein) (Mammalian target of rapamycin) (mTOR) (Mechanistic target of rapamycin) (Rapamycin and FKBP12 target 1) (Rapamycin target protein 1) (Tyrosine-protein kinase mTOR) (EC 2.7.10.2) | Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23426360, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29424687, ECO:0000269|PubMed:29567957, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31695197, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:35926713, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:36691768, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37751742}. |
| P42684 | ABL2 | T858 | ochoa | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P46013 | MKI67 | T1327 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46100 | ATRX | T591 | ochoa | Transcriptional regulator ATRX (EC 3.6.4.12) (ATP-dependent helicase ATRX) (X-linked helicase II) (X-linked nuclear protein) (XNP) (Znf-HX) | Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomeres nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as a negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}. |
| P46109 | CRKL | T130 | ochoa | Crk-like protein | May mediate the transduction of intracellular signals. |
| P46940 | IQGAP1 | T1413 | ochoa | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| P47712 | PLA2G4A | T53 | ochoa | Cytosolic phospholipase A2 (cPLA2) (Phospholipase A2 group IVA) [Includes: Phospholipase A2 (EC 3.1.1.4) (Phosphatidylcholine 2-acylhydrolase); Lysophospholipase (EC 3.1.1.5)] | Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891). {ECO:0000250|UniProtKB:P47713, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:12672805, ECO:0000269|PubMed:14709560, ECO:0000269|PubMed:16617059, ECO:0000269|PubMed:17472963, ECO:0000269|PubMed:18451993, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7794891, ECO:0000269|PubMed:8619991, ECO:0000269|PubMed:8702602, ECO:0000269|PubMed:9425121}. |
| P48751 | SLC4A3 | T1120 | ochoa | Anion exchange protein 3 (AE 3) (Anion exchanger 3) (CAE3/BAE3) (Cardiac/brain band 3-like protein) (Neuronal band 3-like protein) (Solute carrier family 4 member 3) | Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:29167417, PubMed:7923606). May be involved in the regulation of intracellular pH, and the modulation of cardiac action potential (PubMed:29167417). {ECO:0000269|PubMed:29167417, ECO:0000269|PubMed:7923606}. |
| P49327 | FASN | T1053 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49327 | FASN | T1420 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49407 | ARRB1 | T381 | ochoa | Beta-arrestin-1 (Arrestin beta-1) (Non-visual arrestin-2) | Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as a signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as a signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) (By similarity). Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940). {ECO:0000250, ECO:0000269|PubMed:12464600, ECO:0000269|PubMed:14711824, ECO:0000269|PubMed:15475570, ECO:0000269|PubMed:15611106, ECO:0000269|PubMed:15671180, ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:16280323, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:16492667, ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:18337459, ECO:0000269|PubMed:18419762, ECO:0000269|PubMed:19620252, ECO:0000269|PubMed:19643177, ECO:0000269|PubMed:22457824, ECO:0000269|PubMed:23341447, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:23886940}. |
| P49674 | CSNK1E | T44 | psp | Casein kinase I isoform epsilon (CKI-epsilon) (CKIe) (EC 2.7.11.1) | Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (Probable). Participates in Wnt signaling (PubMed:12556519, PubMed:23413191). Phosphorylates DVL1 (PubMed:12556519). Phosphorylates DVL2 (PubMed:23413191). Phosphorylates NEDD9/HEF1 (By similarity). Central component of the circadian clock (PubMed:16790549). In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:15917222, PubMed:16790549). Controls PER1 and PER2 nuclear transport and degradation (By similarity). Inhibits cytokine-induced granuloytic differentiation (PubMed:15070676). {ECO:0000250|UniProtKB:Q9JMK2, ECO:0000269|PubMed:12556519, ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:23413191, ECO:0000305|PubMed:7797465}. |
| P50851 | LRBA | T1782 | ochoa | Lipopolysaccharide-responsive and beige-like anchor protein (Beige-like protein) (CDC4-like protein) | Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). {ECO:0000250|UniProtKB:Q9ESE1, ECO:0000269|PubMed:33773106}. |
| P52597 | HNRNPF | T301 | ochoa | Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] | Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}. |
| P53367 | ARFIP1 | T46 | ochoa | Arfaptin-1 (ADP-ribosylation factor-interacting protein 1) | Plays a role in controlling biogenesis of secretory granules at the trans-Golgi network (PubMed:22981988). Mechanistically, binds ARF-GTP at the neck of a growing secretory granule precursor and forms a protective scaffold (PubMed:22981988, PubMed:9038142). Once the granule precursor has been completely loaded, active PRKD1 phosphorylates ARFIP1 and releases it from ARFs (PubMed:22981988). In turn, ARFs induce fission (PubMed:22981988). Through this mechanism, ensures proper secretory granule formation at the Golgi of pancreatic beta cells (PubMed:22981988). {ECO:0000269|PubMed:22981988, ECO:0000269|PubMed:9038142}. |
| P53667 | LIMK1 | T229 | ochoa | LIM domain kinase 1 (LIMK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11832213, PubMed:12807904, PubMed:15660133, PubMed:16230460, PubMed:18028908, PubMed:22328514, PubMed:23633677). Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop (PubMed:10436159). LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly (PubMed:18028908). Stimulates axonal outgrowth and may be involved in brain development (PubMed:18028908). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23633677}.; FUNCTION: [Isoform 3]: Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). {ECO:0000269|PubMed:10196227}. |
| P54278 | PMS2 | T576 | ochoa | Mismatch repair endonuclease PMS2 (EC 3.1.-.-) (DNA mismatch repair protein PMS2) (PMS1 protein homolog 2) | Component of the post-replicative DNA mismatch repair system (MMR) (PubMed:30653781, PubMed:35189042). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Possesses an ATPase activity, but in the absence of gross structural changes, ATP hydrolysis may not be necessary for proficient mismatch repair (PubMed:35189042). {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:23709753, ECO:0000269|PubMed:30653781, ECO:0000269|PubMed:35189042}. |
| P54652 | HSPA2 | T421 | ochoa | Heat shock-related 70 kDa protein 2 (Heat shock 70 kDa protein 2) (Heat shock protein family A member 2) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity). {ECO:0000250|UniProtKB:P17156, ECO:0000303|PubMed:26865365}. |
| P54753 | EPHB3 | T971 | ochoa | Ephrin type-B receptor 3 (EC 2.7.10.1) (EPH-like tyrosine kinase 2) (EPH-like kinase 2) (Embryonic kinase 2) (EK2) (hEK2) (Tyrosine-protein kinase TYRO6) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt. {ECO:0000269|PubMed:15536074}. |
| P54756 | EPHA5 | T649 | ochoa | Ephrin type-A receptor 5 (EC 2.7.10.1) (Brain-specific kinase) (EPH homology kinase 1) (EHK-1) (EPH-like kinase 7) (EK7) (hEK7) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion (By similarity). {ECO:0000250}. |
| P54760 | EPHB4 | T953 | ochoa | Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}. |
| P55017 | SLC12A3 | T50 | psp | Solute carrier family 12 member 3 (Na-Cl cotransporter) (NCC) (Na-Cl symporter) (Thiazide-sensitive sodium-chloride cotransporter) | Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}. |
| P56537 | EIF6 | T165 | ochoa | Eukaryotic translation initiation factor 6 (eIF-6) (B(2)GCN homolog) (B4 integrin interactor) (CAB) (p27(BBP)) | Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm (PubMed:10085284, PubMed:14654845, PubMed:21536732, PubMed:32669547). Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity). {ECO:0000255|HAMAP-Rule:MF_03132, ECO:0000269|PubMed:10085284, ECO:0000269|PubMed:14654845, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:21536732, ECO:0000269|PubMed:32669547}. |
| P56945 | BCAR1 | T326 | ochoa | Breast cancer anti-estrogen resistance protein 1 (CRK-associated substrate) (Cas scaffolding protein family member 1) (p130cas) | Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion (PubMed:12432078, PubMed:12832404). Implicated in induction of cell migration and cell branching (PubMed:12432078, PubMed:12832404, PubMed:17038317). Involved in the BCAR3-mediated inhibition of TGFB signaling (By similarity). {ECO:0000250|UniProtKB:Q61140, ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:17038317}. |
| P60484 | PTEN | T321 | psp | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (EC 3.1.3.16) (EC 3.1.3.48) (EC 3.1.3.67) (Inositol polyphosphate 3-phosphatase) (EC 3.1.3.-) (Mutated in multiple advanced cancers 1) (Phosphatase and tensin homolog) | Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3 (PubMed:16824732, PubMed:26504226, PubMed:9593664, PubMed:9811831). Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate (PubMed:11418101, PubMed:15979280). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:31492966, PubMed:37279284). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (PubMed:22279049). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (PubMed:26166433). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (PubMed:26166433). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability (PubMed:10468583, PubMed:18716620). {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:10468583, ECO:0000269|PubMed:11418101, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:15979280, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26504226, ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:37279284, ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433, ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9616126, ECO:0000269|PubMed:9811831}.; FUNCTION: [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1. {ECO:0000269|PubMed:23744781}. |
| P60660 | MYL6 | T44 | ochoa | Myosin light polypeptide 6 (17 kDa myosin light chain) (LC17) (Myosin light chain 3) (MLC-3) (Myosin light chain alkali 3) (Myosin light chain A3) (Smooth muscle and nonmuscle myosin light chain alkali 6) | Regulatory light chain of myosin. Does not bind calcium. |
| P60709 | ACTB | T194 | ochoa | Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] | Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}. |
| P61160 | ACTR2 | T238 | psp | Actin-related protein 2 (Actin-like protein 2) | ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9000076). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9000076). Seems to contact the pointed end of the daughter actin filament (PubMed:9000076). In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation (PubMed:29058690). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:17220302, PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:17220302, ECO:0000269|PubMed:29058690, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9000076}. |
| P61225 | RAP2B | T61 | ochoa | Ras-related protein Rap-2b (EC 3.6.5.2) | Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. Involved in EGFR and CHRM3 signaling pathways through stimulation of PLCE1. May play a role in cytoskeletal rearrangements and regulate cell spreading through activation of the effector TNIK. May regulate membrane vesiculation in red blood cells. {ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:15143162, ECO:0000269|PubMed:16540189}. |
| P62258 | YWHAE | T137 | ochoa | 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}. |
| P62491 | RAB11A | T43 | ochoa | Ras-related protein Rab-11A (Rab-11) (EC 3.6.5.2) (YL8) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:15601896, PubMed:15689490, PubMed:17462998, PubMed:19542231, PubMed:20026645, PubMed:20890297, PubMed:21282656, PubMed:26032412). The small Rab GTPase RAB11A regulates endocytic recycling (PubMed:20026645). Forms a functional Rab11/RAB11FIP3/dynein complex that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (PubMed:20026645). Acts as a major regulator of membrane delivery during cytokinesis (PubMed:15601896). Together with MYO5B and RAB8A participates in epithelial cell polarization (PubMed:21282656). Together with Rabin8/RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297). Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells (PubMed:17462998). Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane (PubMed:19542231). Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane (PubMed:15689490). Regulates the recycling of FCGRT (receptor of Fc region of monomeric IgG) to basolateral membranes (By similarity). May also play a role in melanosome transport and release from melanocytes (By similarity). Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation (PubMed:25673879, PubMed:31204173). On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth (PubMed:31204173). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-endososomal dependent export route via interaction with WDR44 (PubMed:32344433). {ECO:0000250|UniProtKB:P62490, ECO:0000250|UniProtKB:P62492, ECO:0000269|PubMed:15601896, ECO:0000269|PubMed:15689490, ECO:0000269|PubMed:17462998, ECO:0000269|PubMed:19542231, ECO:0000269|PubMed:20026645, ECO:0000269|PubMed:20890297, ECO:0000269|PubMed:21282656, ECO:0000269|PubMed:25673879, ECO:0000269|PubMed:26032412, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| P62979 | RPS27A | T55 | ochoa | Ubiquitin-ribosomal protein eS31 fusion protein (Ubiquitin carboxyl extension protein 80) [Cleaved into: Ubiquitin; Small ribosomal subunit protein eS31 (40S ribosomal protein S27a)] | [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. {ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:34239127, ECO:0000303|PubMed:19754430}.; FUNCTION: [Small ribosomal subunit protein eS31]: Component of the 40S subunit of the ribosome (PubMed:23636399, PubMed:9582194). 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:23636399, PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797, ECO:0000305|PubMed:9582194}. |
| P62987 | UBA52 | T55 | ochoa | Ubiquitin-ribosomal protein eL40 fusion protein (CEP52) (Ubiquitin A-52 residue ribosomal protein fusion product 1) [Cleaved into: Ubiquitin; Large ribosomal subunit protein eL40 (60S ribosomal protein L40) (rpL40)] | [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. {ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:34239127, ECO:0000303|PubMed:19754430}.; FUNCTION: [Large ribosomal subunit protein eL40]: Component of the 60S subunit of the ribosome (PubMed:23169626, PubMed:23636399, PubMed:32669547, PubMed:39048817, PubMed:39103523). Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, and especially for cap-dependent translation of vesicular stomatitis virus mRNAs (PubMed:23169626, PubMed:23636399, PubMed:32669547, PubMed:39048817, PubMed:39103523). {ECO:0000269|PubMed:23169626, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000269|PubMed:39048817, ECO:0000269|PubMed:39103523}. |
| P63244 | RACK1 | T50 | psp | Small ribosomal subunit protein RACK1 (Cell proliferation-inducing gene 21 protein) (Guanine nucleotide-binding protein subunit beta-2-like 1) (Guanine nucleotide-binding protein subunit beta-like protein 12.3) (Human lung cancer oncogene 7 protein) (HLC-7) (Receptor for activated C kinase) (Receptor of activated protein C kinase 1) [Cleaved into: Small ribosomal subunit protein RACK1, N-terminally processed (Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed) (Receptor of activated protein C kinase 1, N-terminally processed)] | Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes. Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843). Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6. Inhibits the activity of SRC kinases including SRC, LCK and YES1. Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer. Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC. Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix. Involved in PKC-dependent translocation of ADAM12 to the cell membrane. Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation. Required for PTK2/FAK1 phosphorylation and dephosphorylation. Regulates internalization of the muscarinic receptor CHRM2. Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L. Inhibits TRPM6 channel activity. Regulates cell surface expression of some GPCRs such as TBXA2R. Plays a role in regulation of FLT1-mediated cell migration. Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (PubMed:19674157). Promotes migration of breast carcinoma cells by binding to and activating RHOA (PubMed:20499158). Acts as an adapter for the dephosphorylation and inactivation of AKT1 by promoting recruitment of PP2A phosphatase to AKT1 (By similarity). {ECO:0000250|UniProtKB:P68040, ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:12589061, ECO:0000269|PubMed:12958311, ECO:0000269|PubMed:17108144, ECO:0000269|PubMed:17244529, ECO:0000269|PubMed:17956333, ECO:0000269|PubMed:18088317, ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18621736, ECO:0000269|PubMed:19423701, ECO:0000269|PubMed:19674157, ECO:0000269|PubMed:19785988, ECO:0000269|PubMed:20499158, ECO:0000269|PubMed:20541605, ECO:0000269|PubMed:20573744, ECO:0000269|PubMed:20976005, ECO:0000269|PubMed:21212275, ECO:0000269|PubMed:21347310, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:28132843, ECO:0000269|PubMed:9584165}.; FUNCTION: (Microbial infection) Binds to Y.pseudotuberculosis yopK which leads to inhibition of phagocytosis and survival of bacteria following infection of host cells. {ECO:0000269|PubMed:21347310}.; FUNCTION: (Microbial infection) Enhances phosphorylation of HIV-1 Nef by PKCs. {ECO:0000269|PubMed:11312657}.; FUNCTION: (Microbial infection) In case of poxvirus infection, remodels the ribosomes so that they become optimal for the viral mRNAs (containing poly-A leaders) translation but not for host mRNAs. {ECO:0000269|PubMed:28636603}.; FUNCTION: (Microbial infection) Contributes to the cap-independent internal ribosome entry site (IRES)-mediated translation by some RNA viruses. {ECO:0000269|PubMed:25416947}. |
| P63261 | ACTG1 | T194 | ochoa | Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}. |
| P68104 | EEF1A1 | T82 | ochoa | Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}. |
| P68363 | TUBA1B | T253 | psp | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P78316 | NOP14 | T161 | ochoa | Nucleolar protein 14 (Nucleolar complex protein 14) | Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm (By similarity). {ECO:0000250}. |
| P78347 | GTF2I | T549 | ochoa | General transcription factor II-I (GTFII-I) (TFII-I) (Bruton tyrosine kinase-associated protein 135) (BAP-135) (BTK-associated protein 135) (SRF-Phox1-interacting protein) (SPIN) (Williams-Beuren syndrome chromosomal region 6 protein) | Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C-FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box. Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation. {ECO:0000269|PubMed:10373551, ECO:0000269|PubMed:11373296, ECO:0000269|PubMed:16738337}. |
| P82094 | TMF1 | T291 | ochoa | TATA element modulatory factor (TMF) (Androgen receptor coactivator 160 kDa protein) (Androgen receptor-associated protein of 160 kDa) | Potential coactivator of the androgen receptor. Mediates STAT3 degradation. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER. This protein binds the HIV-1 TATA element and inhibits transcriptional activation by the TATA-binding protein (TBP). {ECO:0000269|PubMed:10428808, ECO:0000269|PubMed:1409643, ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:17698061}. |
| P85037 | FOXK1 | T651 | 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}. |
| Q00013 | MPP1 | T123 | ochoa | 55 kDa erythrocyte membrane protein (p55) (Membrane protein, palmitoylated 1) | Essential regulator of neutrophil polarity. Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity (By similarity). {ECO:0000250}. |
| Q01814 | ATP2B2 | T1139 | psp | Plasma membrane calcium-transporting ATPase 2 (PMCA2) (EC 7.2.2.10) (Plasma membrane calcium ATPase isoform 2) (Plasma membrane calcium pump isoform 2) | ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:15829536, PubMed:17234811). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment (PubMed:15829536, PubMed:17234811). Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics. At parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+) efflux in response to climbing fiber-induced Ca(2+) rise. Provides for fast return of Ca(2+) concentrations back to their resting levels, ultimately contributing to long-term depression induction and motor learning (By similarity). Plays an essential role in hearing and balance (PubMed:15829536, PubMed:17234811). In cochlear hair cells, shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates Ca(2+) transients generated by the opening of the mechanoelectrical transduction channels. Regulates Ca(2+) levels in the vestibular system, where it contributes to the formation of otoconia (PubMed:15829536, PubMed:17234811). In non-excitable cells, regulates Ca(2+) signaling through spatial control of Ca(2+) ions extrusion and dissipation of Ca(2+) transients generated by store-operated channels (PubMed:25690014). In lactating mammary gland, allows for the high content of Ca(2+) ions in the milk (By similarity). {ECO:0000250|UniProtKB:Q9R0K7, ECO:0000269|PubMed:15829536, ECO:0000269|PubMed:17234811, ECO:0000269|PubMed:25690014}. |
| Q02156 | PRKCE | T228 | ochoa | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
| Q03188 | CENPC | T167 | ochoa | Centromere protein C (CENP-C) (Centromere autoantigen C) (Centromere protein C 1) (CENP-C 1) (Interphase centromere complex protein 7) | Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions. {ECO:0000269|PubMed:19482874, ECO:0000269|PubMed:21529714}. |
| Q05397 | PTK2 | T474 | psp | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| Q06710 | PAX8 | T283 | ochoa | Paired box protein Pax-8 | Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells. |
| Q07020 | RPL18 | T56 | ochoa | Large ribosomal subunit protein eL18 (60S ribosomal protein L18) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| Q08477 | CYP4F3 | T233 | ochoa | Cytochrome P450 4F3 (EC 1.14.14.1) (20-hydroxyeicosatetraenoic acid synthase) (20-HETE synthase) (CYPIVF3) (Cytochrome P450-LTB-omega) (Docosahexaenoic acid omega-hydroxylase CYP4F3) (EC 1.14.14.79) (Leukotriene-B(4) 20-monooxygenase 2) (Leukotriene-B(4) omega-hydroxylase 2) (EC 1.14.14.94) | A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins) (PubMed:11461919, PubMed:15145985, PubMed:16547005, PubMed:16820285, PubMed:18065749, PubMed:18182499, PubMed:18577768, PubMed:8486631, PubMed:9675028). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9675028). May play a role in inactivation of pro-inflammatory and anti-inflammatory oxylipins during the resolution of inflammation (PubMed:11461919, PubMed:15145985, PubMed:15364545, PubMed:16547005, PubMed:16820285, PubMed:18065749, PubMed:18182499, PubMed:18577768, PubMed:8486631, PubMed:9675028). {ECO:0000269|PubMed:11461919, ECO:0000269|PubMed:15145985, ECO:0000269|PubMed:15364545, ECO:0000269|PubMed:16547005, ECO:0000269|PubMed:16820285, ECO:0000269|PubMed:18065749, ECO:0000269|PubMed:18182499, ECO:0000269|PubMed:18577768, ECO:0000269|PubMed:8486631, ECO:0000269|PubMed:9675028}.; FUNCTION: [Isoform CYP4F3A]: Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of oxylipins in myeloid cells, displaying higher affinity for arachidonate metabolite leukotriene B4 (LTB4) (PubMed:11461919, PubMed:15364545, PubMed:8486631, PubMed:9675028). Inactivates LTB4 via three successive oxidative transformations to 20-hydroxy-LTB4, then to 20-oxo-LTB4 and to 20-carboxy-LTB4 (PubMed:9675028). Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate (PubMed:15145985). Omega-hydroxylates monohydroxy polyunsaturated fatty acids (PUFAs), including hydroxyeicosatetraenoates (HETEs) and hydroxyeicosapentaenoates (HEPEs), to dihydroxy compounds (PubMed:15364545, PubMed:9675028). Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acid, thereby initiating chain shortening (PubMed:18182499). Has low hydroxylase activity toward PUFAs (PubMed:11461919, PubMed:18577768). {ECO:0000269|PubMed:11461919, ECO:0000269|PubMed:15145985, ECO:0000269|PubMed:15364545, ECO:0000269|PubMed:18182499, ECO:0000269|PubMed:18577768, ECO:0000269|PubMed:8486631, ECO:0000269|PubMed:9675028}.; FUNCTION: [Isoform CYP4F3B]: Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of polyunsaturated fatty acids (PUFAs) (PubMed:11461919, PubMed:16820285, PubMed:18577768). Participates in the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:11461919, PubMed:16820285, PubMed:18577768). Has high omega-hydroxylase activity toward other PUFAs, including eicosatrienoic acid (ETA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (PubMed:16820285, PubMed:18577768). Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of PUFAs with lower efficiency (PubMed:18577768). Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid and hexacosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acids, thereby initiating chain shortening (PubMed:16547005, PubMed:18182499). Omega-hydroxylates long-chain 3-hydroxy fatty acids, likely initiating the oxidative conversion to the corresponding 3-hydroxydicarboxylic fatty acids (PubMed:18065749). Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate (PubMed:15145985). {ECO:0000269|PubMed:11461919, ECO:0000269|PubMed:15145985, ECO:0000269|PubMed:16547005, ECO:0000269|PubMed:16820285, ECO:0000269|PubMed:18065749, ECO:0000269|PubMed:18182499, ECO:0000269|PubMed:18577768}. |
| Q08AD1 | CAMSAP2 | T1089 | ochoa | Calmodulin-regulated spectrin-associated protein 2 (Calmodulin-regulated spectrin-associated protein 1-like protein 1) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153, PubMed:24706919). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:27666745). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (PubMed:24908486). Through the microtubule cytoskeleton, regulates the autophagosome transport (PubMed:28726242). {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:24908486, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28726242}. |
| Q12778 | FOXO1 | T467 | ochoa | Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma) | Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:15890677, PubMed:18356527, PubMed:19221179, PubMed:20543840, PubMed:21245099). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:10358076). Activity suppressed by insulin (PubMed:10358076). Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). Acts as an inhibitor of glucose sensing in pancreatic beta cells by acting as a transcription repressor and suppressing expression of PDX1 (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Also promotes gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1 (PubMed:17024043). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (PubMed:18356527, PubMed:19221179). Promotes neural cell death (PubMed:18356527). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (PubMed:20543840). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Positive regulator of apoptosis in cardiac smooth muscle cells as a result of its transcriptional activation of pro-apoptotic genes (PubMed:19483080). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). {ECO:0000250|UniProtKB:A4L7N3, ECO:0000250|UniProtKB:G3V7R4, ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:10358076, ECO:0000269|PubMed:12228231, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:17024043, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:19221179, ECO:0000269|PubMed:19483080, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:31063815}. |
| Q12874 | SF3A3 | T298 | ochoa | Splicing factor 3A subunit 3 (SF3a60) (Spliceosome-associated protein 61) (SAP 61) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10882114, PubMed:11533230, PubMed:32494006, PubMed:34822310, PubMed:8022796). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:10882114, PubMed:11533230, PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3A3 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes (PubMed:29360106, PubMed:30315277). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:11533230, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:34822310, ECO:0000269|PubMed:8022796}. |
| Q12888 | TP53BP1 | T855 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | T1012 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | T1166 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12913 | PTPRJ | T1314 | ochoa | Receptor-type tyrosine-protein phosphatase eta (Protein-tyrosine phosphatase eta) (R-PTP-eta) (EC 3.1.3.48) (Density-enhanced phosphatase 1) (DEP-1) (HPTP eta) (Protein-tyrosine phosphatase receptor type J) (R-PTP-J) (CD antigen CD148) | Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2 (PubMed:10821867, PubMed:12062403, PubMed:12370829, PubMed:12475979, PubMed:18348712, PubMed:19494114, PubMed:19922411, PubMed:21262971). Plays a role in cell adhesion, migration, proliferation and differentiation (PubMed:12370829, PubMed:14709717, PubMed:16682945, PubMed:19836242). Has a role in megakaryocytes and platelet formation (PubMed:30591527). Involved in vascular development (By similarity). Regulator of macrophage adhesion and spreading (By similarity). Positively affects cell-matrix adhesion (By similarity). Positive regulator of platelet activation and thrombosis. Negative regulator of cell proliferation (PubMed:16682945). Negative regulator of PDGF-stimulated cell migration; through dephosphorylation of PDGFR (PubMed:21091576). Positive regulator of endothelial cell survival, as well as of VEGF-induced SRC and AKT activation; through KDR dephosphorylation (PubMed:18936167). Negative regulator of EGFR signaling pathway; through EGFR dephosphorylation (PubMed:19836242). Enhances the barrier function of epithelial junctions during reassembly (PubMed:19332538). Negatively regulates T-cell receptor (TCR) signaling (PubMed:11259588, PubMed:9531590, PubMed:9780142). Upon T-cell TCR activation, it is up-regulated and excluded from the immunological synapses, while upon T-cell-antigen presenting cells (APC) disengagement, it is no longer excluded and can dephosphorylate PLCG1 and LAT to down-regulate prolongation of signaling (PubMed:11259588, PubMed:12913111). {ECO:0000250|UniProtKB:Q64455, ECO:0000269|PubMed:10821867, ECO:0000269|PubMed:11259588, ECO:0000269|PubMed:12062403, ECO:0000269|PubMed:12370829, ECO:0000269|PubMed:12475979, ECO:0000269|PubMed:12913111, ECO:0000269|PubMed:14709717, ECO:0000269|PubMed:16682945, ECO:0000269|PubMed:18348712, ECO:0000269|PubMed:18936167, ECO:0000269|PubMed:19332538, ECO:0000269|PubMed:19494114, ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:19922411, ECO:0000269|PubMed:21091576, ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:30591527, ECO:0000269|PubMed:9531590, ECO:0000269|PubMed:9780142}.; FUNCTION: [Isoform 2]: Activates angiogenesis and cell migration (PubMed:28052032). Downregulates the expression of the endothelial adhesion molecules ICAM1 and VCAM1 (PubMed:28052032). {ECO:0000269|PubMed:28052032}. |
| Q12929 | EPS8 | T699 | ochoa | Epidermal growth factor receptor kinase substrate 8 | Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes. {ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031}. |
| Q12968 | NFATC3 | T343 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 3 (NF-ATc3) (NFATc3) (NFATx) (T-cell transcription factor NFAT4) (NF-AT4) (NF-AT4c) | Acts as a regulator of transcriptional activation. Binds to the TNFSF11/RANKL promoter region and promotes TNFSF11 transcription (By similarity). Binding to the TNFSF11 promoter region is increased by high levels of Ca(2+) which induce NFATC3 expression and may lead to regulation of TNFSF11 expression in osteoblasts (By similarity). Plays a role in promoting mesenteric arterial wall remodeling in response to the intermittent hypoxia-induced increase in EDN1 and ROCK signaling (By similarity). As a result NFATC3 colocalizes with F-actin filaments, translocates to the nucleus and promotes transcription of the smooth muscle hypertrophy and differentiation marker ACTA2 (By similarity). Promotes lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC4 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). In conjunction with NFATC4, involved in embryonic heart development via maintenance of cardiomyocyte survival, proliferation and differentiation (By similarity). Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (PubMed:18815128). Required for thymocyte maturation during DN3 to DN4 transition and during positive selection (By similarity). Positively regulates macrophage-derived polymicrobial clearance, via binding to the promoter region and promoting transcription of NOS2 resulting in subsequent generation of nitric oxide (By similarity). Involved in Ca(2+)-mediated transcriptional responses upon Ca(2+) influx via ORAI1 CRAC channels. {ECO:0000250|UniProtKB:A0A0G2JTY4, ECO:0000250|UniProtKB:P97305, ECO:0000269|PubMed:18815128, ECO:0000269|PubMed:32415068}. |
| Q13148 | TARDBP | T116 | ochoa|psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q13177 | PAK2 | T162 | ochoa | Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. |
| Q13263 | TRIM28 | T498 | 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 | T626 | 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}. |
| Q13535 | ATR | T1578 | psp | Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (FRAP-related protein 1) | Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:27723717, PubMed:27723720, PubMed:30139873, PubMed:33848395, PubMed:37788673, PubMed:37832547, PubMed:9427750, PubMed:9636169). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:23273981, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:9427750, PubMed:9636169). Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis (PubMed:11114888, PubMed:11418864, PubMed:11865061, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:9925639). Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (PubMed:11673449). Required for FANCD2 ubiquitination (PubMed:15314022). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (PubMed:12526805). Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (PubMed:30139873). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (PubMed:25083873, PubMed:37788673, PubMed:37832547). Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1 (PubMed:25083873). Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (PubMed:37832547). Involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture (PubMed:37788673). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (PubMed:37788673). Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity). {ECO:0000250|UniProtKB:Q9JKK8, ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:10608806, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12526805, ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:14742437, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15496423, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:33848395, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9636169, ECO:0000269|PubMed:9925639}. |
| Q13813 | SPTAN1 | T1552 | ochoa | Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin) (Fodrin alpha chain) (Spectrin, non-erythroid alpha subunit) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. |
| Q13895 | BYSL | T160 | ochoa | Bystin | Required for processing of 20S pre-rRNA precursor and biogenesis of 40S ribosomal subunits. May be required for trophinin-dependent regulation of cell adhesion during implantation of human embryos. {ECO:0000269|PubMed:17360433, ECO:0000269|PubMed:17381424}. |
| Q14004 | CDK13 | T1480 | ochoa | Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) | Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}. |
| Q14126 | DSG2 | T1056 | ochoa | Desmoglein-2 (Cadherin family member 5) (HDGC) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:38395410). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Required for proliferation and viability of embryonic stem cells in the blastocyst, thereby crucial for progression of post-implantation embryonic development (By similarity). Maintains pluripotency by regulating epithelial to mesenchymal transition/mesenchymal to epithelial transition (EMT/MET) via interacting with and sequestering CTNNB1 to sites of cell-cell contact, thereby reducing translocation of CTNNB1 to the nucleus and subsequent transcription of CTNNB1/TCF-target genes (PubMed:29910125). Promotes pluripotency and the multi-lineage differentiation potential of hematopoietic stem cells (PubMed:27338829). Plays a role in endothelial cell sprouting and elongation via mediating the junctional-association of cortical actin fibers and CDH5 (PubMed:27338829). Plays a role in limiting inflammatory infiltration and the apoptotic response to injury in kidney tubular epithelial cells, potentially via its role in maintaining cell-cell adhesion and the epithelial barrier (PubMed:38395410). {ECO:0000250|UniProtKB:O55111, ECO:0000269|PubMed:27338829, ECO:0000269|PubMed:29910125, ECO:0000269|PubMed:38395410}. |
| Q14149 | MORC3 | T494 | ochoa | MORC family CW-type zinc finger protein 3 (Nuclear matrix protein 2) (Zinc finger CW-type coiled-coil domain protein 3) | Nuclear matrix protein which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism and plays a role in innate immunity by restricting different viruses through modulation of the IFN response (PubMed:27440897, PubMed:34759314). Mechanistically, possesses a primary antiviral function through a MORC3-regulated element that activates IFNB1, and this function is guarded by a secondary IFN-repressing function (PubMed:34759314). Sumoylated MORC3-NBs associates with PML-NBs and recruits TP53 and SP100, thus regulating TP53 activity (PubMed:17332504, PubMed:20501696). Binds RNA in vitro (PubMed:11927593). Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) 'Lys-4' on histone H3 (PubMed:26933034). The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0 (PubMed:26933034). {ECO:0000269|PubMed:11927593, ECO:0000269|PubMed:17332504, ECO:0000269|PubMed:20501696, ECO:0000269|PubMed:26933034, ECO:0000269|PubMed:27440897, ECO:0000269|PubMed:34759314}.; FUNCTION: (Microbial infection) May be required for influenza A transcription during viral infection (PubMed:26202233). {ECO:0000269|PubMed:26202233}. |
| Q14151 | SAFB2 | T277 | 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. |
| Q14194 | CRMP1 | T102 | psp | Dihydropyrimidinase-related protein 1 (DRP-1) (Collapsin response mediator protein 1) (CRMP-1) (Inactive dihydropyrimidinase) (Unc-33-like phosphoprotein 3) (ULIP-3) | Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (PubMed:25358863). Plays a role in axon guidance (PubMed:25358863). During the axon guidance process, acts downstream of SEMA3A to promote FLNA dissociation from F-actin which results in the rearrangement of the actin cytoskeleton and the collapse of the growth cone (PubMed:25358863). Involved in invasive growth and cell migration (PubMed:11562390). May participate in cytokinesis (PubMed:19799413). {ECO:0000269|PubMed:11562390, ECO:0000269|PubMed:19799413, ECO:0000269|PubMed:25358863}. |
| Q14324 | MYBPC2 | T830 | ochoa | Myosin-binding protein C, fast-type (Fast MyBP-C) (C-protein, skeletal muscle fast isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role. |
| Q14511 | NEDD9 | T804 | psp | Enhancer of filamentation 1 (hEF1) (CRK-associated substrate-related protein) (CAS-L) (CasL) (Cas scaffolding protein family member 2) (CASS2) (Neural precursor cell expressed developmentally down-regulated protein 9) (NEDD-9) (Renal carcinoma antigen NY-REN-12) (p105) [Cleaved into: Enhancer of filamentation 1 p55] | Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion (PubMed:24574519). As a focal adhesion protein, plays a role in embryonic fibroblast migration (By similarity). May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKL and SHPTP2 to the tyrosine phosphorylated form (PubMed:9020138). Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs (PubMed:17174122). Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse (By similarity). Negatively regulates cilia outgrowth in polarized cysts (By similarity). Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723). Positively regulates RANKL-induced osteoclastogenesis (By similarity). Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory (By similarity). {ECO:0000250|UniProtKB:A0A8I3PDQ1, ECO:0000250|UniProtKB:O35177, ECO:0000269|PubMed:17174122, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:24574519, ECO:0000269|PubMed:9020138}. |
| Q14524 | SCN5A | T101 | psp | Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1) | Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). {ECO:0000250|UniProtKB:Q9JJV9, ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}. |
| Q14680 | MELK | T56 | psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q14680 | MELK | T539 | psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q14684 | RRP1B | T693 | psp | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14814 | MEF2D | T286 | ochoa | Myocyte-specific enhancer factor 2D | Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity). {ECO:0000250, ECO:0000269|PubMed:10849446, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15743823, ECO:0000269|PubMed:15834131}. |
| Q15042 | RAB3GAP1 | T663 | ochoa | Rab3 GTPase-activating protein catalytic subunit (RAB3 GTPase-activating protein 130 kDa subunit) (Rab3-GAP p130) (Rab3-GAP) | Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide exchange factor (GEF) activity towards RAB18 (PubMed:10859313, PubMed:24891604, PubMed:9030515). As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP (PubMed:10859313). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones (PubMed:15696165). The Rab3GAP complex, acts as a GEF for RAB18 by promoting the conversion of inactive RAB18-GDP to the active form RAB18-GTP (PubMed:24891604). Recruits and stabilizes RAB18 at the cis-Golgi membrane in fibroblasts where RAB18 is most likely activated (PubMed:26063829). Also involved in RAB18 recruitment at the endoplasmic reticulum (ER) membrane where it maintains proper ER structure (PubMed:24891604). Required for normal eye and brain development (PubMed:15696165, PubMed:23420520). May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters (PubMed:9030515, PubMed:9852129). {ECO:0000269|PubMed:10859313, ECO:0000269|PubMed:15696165, ECO:0000269|PubMed:23420520, ECO:0000269|PubMed:24891604, ECO:0000269|PubMed:26063829, ECO:0000269|PubMed:9030515, ECO:0000269|PubMed:9852129}. |
| Q15131 | CDK10 | T133 | psp | Cyclin-dependent kinase 10 (EC 2.7.11.22) (Cell division protein kinase 10) (Serine/threonine-protein kinase PISSLRE) | Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells) (PubMed:24218572). Involved in the regulation of actin cytoskeleton organization through the phosphorylation of actin dynamics regulators such as PKN2. Is a negative regulator of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling (PubMed:27104747). {ECO:0000269|PubMed:24218572, ECO:0000269|PubMed:27104747}. |
| Q15424 | SAFB | T278 | 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}. |
| Q15650 | TRIP4 | T275 | ochoa | Activating signal cointegrator 1 (ASC-1) (Thyroid receptor-interacting protein 4) (TR-interacting protein 4) (TRIP-4) | Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription (PubMed:10454579, PubMed:25219498). May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions (PubMed:10454579, PubMed:25219498). Plays a role in thyroid hormone receptor and estrogen receptor transactivation (PubMed:10454579, PubMed:25219498). Also involved in androgen receptor transactivation (By similarity). Plays a pivotal role in the transactivation of NF-kappa-B, SRF and AP1 (PubMed:12077347). Acts as a mediator of transrepression between nuclear receptor and either AP1 or NF-kappa-B (PubMed:12077347). May play a role in the development of neuromuscular junction (PubMed:26924529). May play a role in late myogenic differentiation (By similarity). Also functions as part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (PubMed:32099016, PubMed:32579943, PubMed:36302773). {ECO:0000250|UniProtKB:Q9QXN3, ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:26924529, ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773}. |
| Q15831 | STK11 | T189 | psp | Serine/threonine-protein kinase STK11 (EC 2.7.11.1) (Liver kinase B1) (LKB1) (hLKB1) (Renal carcinoma antigen NY-REN-19) | Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.; FUNCTION: [Isoform 2]: Has a role in spermiogenesis. {ECO:0000250}. |
| Q15907 | RAB11B | T43 | ochoa | Ras-related protein Rab-11B (EC 3.6.5.2) (GTP-binding protein YPT3) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:14627637, PubMed:19029296, PubMed:19244346, PubMed:20717956, PubMed:21248079, PubMed:22129970, PubMed:26032412). The small Rab GTPase RAB11B plays a role in endocytic recycling, regulating apical recycling of several transmembrane proteins including cystic fibrosis transmembrane conductance regulator/CFTR, epithelial sodium channel/ENaC, potassium voltage-gated channel, and voltage-dependent L-type calcium channel. May also regulate constitutive and regulated secretion, like insulin granule exocytosis. Required for melanosome transport and release from melanocytes. Also regulates V-ATPase intracellular transport in response to extracellular acidosis (PubMed:14627637, PubMed:19029296, PubMed:19244346, PubMed:20717956, PubMed:21248079, PubMed:22129970). Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation (PubMed:25673879). On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth (PubMed:31204173). {ECO:0000269|PubMed:14627637, ECO:0000269|PubMed:19029296, ECO:0000269|PubMed:19244346, ECO:0000269|PubMed:20717956, ECO:0000269|PubMed:21248079, ECO:0000269|PubMed:22129970, ECO:0000269|PubMed:25673879, ECO:0000269|PubMed:26032412, ECO:0000269|PubMed:31204173}. |
| Q15911 | ZFHX3 | T1582 | ochoa | Zinc finger homeobox protein 3 (AT motif-binding factor 1) (AT-binding transcription factor 1) (Alpha-fetoprotein enhancer-binding protein) (Zinc finger homeodomain protein 3) (ZFH-3) | Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signaling can repress the transcription of AFP via its interaction with SMAD2/3 (PubMed:25105025). Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain (By similarity). Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression (PubMed:11312261). Down-regulates the MUC5AC promoter in gastric cancer (PubMed:17330845). In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712). Inhibits estrogen receptor (ESR1) function by selectively competing with coactivator NCOA3 for binding to ESR1 in ESR1-positive breast cancer cells (PubMed:20720010). {ECO:0000250|UniProtKB:Q61329, ECO:0000269|PubMed:11312261, ECO:0000269|PubMed:17330845, ECO:0000269|PubMed:20599712, ECO:0000269|PubMed:20720010, ECO:0000269|PubMed:25105025}. |
| Q16832 | DDR2 | T765 | ochoa | Discoidin domain-containing receptor 2 (Discoidin domain receptor 2) (EC 2.7.10.1) (CD167 antigen-like family member B) (Discoidin domain-containing receptor tyrosine kinase 2) (Neurotrophic tyrosine kinase, receptor-related 3) (Receptor protein-tyrosine kinase TKT) (Tyrosine-protein kinase TYRO10) (CD antigen CD167b) | Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416, ECO:0000269|PubMed:9659899}. |
| Q16832 | DDR2 | T766 | ochoa | Discoidin domain-containing receptor 2 (Discoidin domain receptor 2) (EC 2.7.10.1) (CD167 antigen-like family member B) (Discoidin domain-containing receptor tyrosine kinase 2) (Neurotrophic tyrosine kinase, receptor-related 3) (Receptor protein-tyrosine kinase TKT) (Tyrosine-protein kinase TYRO10) (CD antigen CD167b) | Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416, ECO:0000269|PubMed:9659899}. |
| Q2VPB7 | AP5B1 | T212 | ochoa | AP-5 complex subunit beta-1 (Adaptor-related protein complex 5 beta subunit) (Beta5) | As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. {ECO:0000269|PubMed:22022230}. |
| Q3V6T2 | CCDC88A | T1593 | ochoa | Girdin (Akt phosphorylation enhancer) (APE) (Coiled-coil domain-containing protein 88A) (G alpha-interacting vesicle-associated protein) (GIV) (Girders of actin filament) (Hook-related protein 1) (HkRP1) | Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:16139227, PubMed:19211784, PubMed:20462955, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382). {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}. |
| Q49A88 | CCDC14 | T699 | ochoa | Coiled-coil domain-containing protein 14 | Negatively regulates centriole duplication. Negatively regulates CEP63 and CDK2 centrosomal localization. {ECO:0000269|PubMed:24613305, ECO:0000269|PubMed:26297806}. |
| Q53EV4 | LRRC23 | T49 | ochoa | Leucine-rich repeat-containing protein 23 (Leucine-rich protein B7) | Essential for sperm motility and male fertility. Plays an important role in the proper assembly of the third radial spoke (RS3) head and the bridge structure between RS2 and RS3 in the sperm flagella. {ECO:0000269|PubMed:37804054, ECO:0000269|PubMed:38091523}. |
| Q53EZ4 | CEP55 | T154 | ochoa | Centrosomal protein of 55 kDa (Cep55) (Up-regulated in colon cancer 6) | Plays a role in mitotic exit and cytokinesis (PubMed:16198290, PubMed:17853893). Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis (PubMed:17853893). Not required for microtubule nucleation (PubMed:16198290). Plays a role in the development of the brain and kidney (PubMed:28264986). {ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:28264986}. |
| Q53HL2 | CDCA8 | T88 | psp | Borealin (Cell division cycle-associated protein 8) (Dasra-B) (hDasra-B) (Pluripotent embryonic stem cell-related gene 3 protein) | Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment. {ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:15260989, ECO:0000269|PubMed:16571674, ECO:0000269|PubMed:18243099}. |
| Q5JSL3 | DOCK11 | T433 | ochoa | Dedicator of cytokinesis protein 11 (Activated Cdc42-associated guanine nucleotide exchange factor) (ACG) (Zizimin-2) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP (PubMed:37342957). Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology (By similarity). Facilitates filopodia formation through the activation of CDC42 (PubMed:37342957). {ECO:0000250|UniProtKB:A2AF47, ECO:0000269|PubMed:37342957}. |
| Q5JTC6 | AMER1 | T317 | ochoa | APC membrane recruitment protein 1 (Amer1) (Protein FAM123B) (Wilms tumor gene on the X chromosome protein) | Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex. Acts both as a positive and negative regulator of the Wnt signaling pathway, depending on the context: acts as a positive regulator by promoting LRP6 phosphorylation. Also acts as a negative regulator by acting as a scaffold protein for the beta-catenin destruction complex and promoting stabilization of Axin at the cell membrane. Promotes CTNNB1 ubiquitination and degradation. Involved in kidney development. {ECO:0000269|PubMed:17510365, ECO:0000269|PubMed:17925383, ECO:0000269|PubMed:19416806, ECO:0000269|PubMed:21304492, ECO:0000269|PubMed:21498506}. |
| Q5R372 | RABGAP1L | T110 | ochoa | Rab GTPase-activating protein 1-like | GTP-hydrolysis activating protein (GAP) for small GTPase RAB22A, converting active RAB22A-GTP to the inactive form RAB22A-GDP (PubMed:16923123). Plays a role in endocytosis and intracellular protein transport. Recruited by ANK2 to phosphatidylinositol 3-phosphate (PI3P)-positive early endosomes, where it inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:A6H6A9, ECO:0000269|PubMed:16923123}. |
| Q5SW79 | CEP170 | T682 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5T0W9 | FAM83B | T305 | ochoa | Protein FAM83B | Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. {ECO:0000269|PubMed:22886302, ECO:0000269|PubMed:23676467, ECO:0000269|PubMed:23912460}. |
| Q5T5Y3 | CAMSAP1 | T830 | ochoa | Calmodulin-regulated spectrin-associated protein 1 | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}. |
| Q5T7B8 | KIF24 | T494 | ochoa | Kinesin-like protein KIF24 | Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles. Mediates depolymerization of microtubules of centriolar origin, possibly to suppress aberrant cilia formation (PubMed:21620453). Following activation by NEK2 involved in disassembly of primary cilium during G2/M phase but does not disassemble fully formed ciliary axonemes. As cilium assembly and disassembly is proposed to coexist in a dynamic equilibrium may suppress nascent cilium assembly and, potentially, ciliar re-assembly in cells that have already disassembled their cilia ensuring the completion of cilium removal in the later stages of the cell cycle (PubMed:26290419). Plays an important role in recruiting MPHOSPH9, a negative regulator of cilia formation to the distal end of mother centriole (PubMed:30375385). {ECO:0000269|PubMed:21620453, ECO:0000269|PubMed:26290419, ECO:0000269|PubMed:30375385}. |
| Q5T7P8 | SYT6 | T417 | psp | Synaptotagmin-6 (Synaptotagmin VI) (SytVI) | May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. May mediate Ca(2+)-regulation of exocytosis in acrosomal reaction in sperm (By similarity). {ECO:0000250|UniProtKB:Q9R0N8}. |
| Q5T8D3 | ACBD5 | T263 | ochoa | Acyl-CoA-binding domain-containing protein 5 | Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters. {ECO:0000269|PubMed:24535825}. |
| Q5UIP0 | RIF1 | T971 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5UIP0 | RIF1 | T1473 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5VT06 | CEP350 | T669 | ochoa | Centrosome-associated protein 350 (Cep350) (Centrosome-associated protein of 350 kDa) | Plays an essential role in centriole growth by stabilizing a procentriolar seed composed of at least, SASS6 and CPAP (PubMed:19052644). Required for anchoring microtubules to the centrosomes and for the integrity of the microtubule network (PubMed:16314388, PubMed:17878239, PubMed:28659385). Recruits PPARA to discrete subcellular compartments and thereby modulates PPARA activity (PubMed:15615782). Required for ciliation (PubMed:28659385). {ECO:0000269|PubMed:15615782, ECO:0000269|PubMed:16314388, ECO:0000269|PubMed:17878239, ECO:0000269|PubMed:19052644, ECO:0000269|PubMed:28659385}. |
| Q5VTE0 | EEF1A1P5 | T82 | ochoa | Putative elongation factor 1-alpha-like 3 (EF-1-alpha-like 3) (Eukaryotic elongation factor 1 A-like 3) (eEF1A-like 3) (Eukaryotic translation elongation factor 1 alpha-1 pseudogene 5) | This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. {ECO:0000250}. |
| Q5VTT5 | MYOM3 | T1143 | ochoa | Myomesin-3 (Myomesin family member 3) | May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle. {ECO:0000250}. |
| Q5VWQ8 | DAB2IP | T799 | ochoa | Disabled homolog 2-interacting protein (DAB2 interaction protein) (DAB2-interacting protein) (ASK-interacting protein 1) (AIP-1) (DOC-2/DAB-2 interactive protein) | Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Also plays a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to pro-inflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Also mediates TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6), Ras and RAB40C (PubMed:29156729). Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Also functions as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively. {ECO:0000269|PubMed:12813029, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:18292600, ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930, ECO:0000269|PubMed:22696229, ECO:0000269|PubMed:29156729}. |
| Q5VZ89 | DENND4C | T1209 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5VZ89 | DENND4C | T1212 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5VZK9 | CARMIL1 | T912 | ochoa | F-actin-uncapping protein LRRC16A (CARMIL homolog) (Capping protein regulator and myosin 1 linker protein 1) (Capping protein, Arp2/3 and myosin-I linker homolog 1) (Capping protein, Arp2/3 and myosin-I linker protein 1) (Leucine-rich repeat-containing protein 16A) | Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:19846667). {ECO:0000269|PubMed:16054028, ECO:0000269|PubMed:19846667}. |
| Q658Y4 | FAM91A1 | T375 | ochoa | Protein FAM91A1 | As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1. {ECO:0000269|PubMed:29426865}. |
| Q66K14 | TBC1D9B | T1148 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q68CZ2 | TNS3 | T712 | ochoa | Tensin-3 (EC 3.1.3.-) (Tensin-like SH2 domain-containing protein 1) (Tumor endothelial marker 6) | May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, ECO:0000269|PubMed:35687021, ECO:0000305}. |
| Q68DA7 | FMN1 | T612 | ochoa | Formin-1 (Limb deformity protein homolog) | Plays a role in the formation of adherens junction and the polymerization of linear actin cables. {ECO:0000250}. |
| Q68DN1 | SPATA31H1 | T186 | ochoa | Spermatogenesis-associated protein 31H1 | None |
| Q6IAA8 | LAMTOR1 | T48 | ochoa | Ragulator complex protein LAMTOR1 (Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1) (Lipid raft adaptor protein p18) (Protein associated with DRMs and endosomes) (p27Kip1-releasing factor from RhoA) (p27RF-Rho) | Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:20381137, PubMed:22980980, PubMed:29158492). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:22980980, PubMed:28935770, PubMed:29158492, PubMed:30181260, PubMed:31001086, PubMed:32686708, PubMed:36476874). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:20381137, PubMed:22980980, PubMed:29158492). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:31001086, PubMed:32686708). LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes (PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29285400). Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (By similarity). Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes (PubMed:20381137, PubMed:22980980). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (PubMed:20544018). May also play a role in RHOA activation (PubMed:19654316). {ECO:0000250|UniProtKB:Q9CQ22, ECO:0000269|PubMed:19654316, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29107538, ECO:0000269|PubMed:29123114, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:29285400, ECO:0000269|PubMed:30181260, ECO:0000269|PubMed:31001086, ECO:0000269|PubMed:32686708, ECO:0000269|PubMed:36476874}. |
| Q6IQ55 | TTBK2 | T322 | ochoa | Tau-tubulin kinase 2 (EC 2.7.11.1) | Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). Required for recruitment of CPLANE2 and INTU to the mother centriole (By similarity). {ECO:0000250|UniProtKB:Q3UVR3, ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541, ECO:0000269|PubMed:30375385}. |
| Q6NUP7 | PPP4R4 | T147 | ochoa | Serine/threonine-protein phosphatase 4 regulatory subunit 4 | Putative regulatory subunit of serine/threonine-protein phosphatase 4. |
| Q6NZI2 | CAVIN1 | T302 | ochoa | Caveolae-associated protein 1 (Cavin-1) (Polymerase I and transcript release factor) | Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues (PubMed:18056712, PubMed:18191225, PubMed:19726876). Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1). Essential for normal oligomerization of CAV1. Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop. Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template (By similarity) (PubMed:18056712, PubMed:18191225, PubMed:19726876). The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A (By similarity). {ECO:0000250|UniProtKB:O54724, ECO:0000269|PubMed:18056712, ECO:0000269|PubMed:18191225, ECO:0000269|PubMed:19726876}. |
| Q6P3S1 | DENND1B | T577 | ochoa | DENN domain-containing protein 1B (Connecdenn 2) (Protein FAM31B) | Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822). {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:24520163, ECO:0000269|PubMed:26774822}. |
| Q6P995 | FAM171B | T403 | ochoa | Protein FAM171B | None |
| Q6W2J9 | BCOR | T773 | 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}. |
| Q6ZMI0 | PPP1R21 | T650 | ochoa | Protein phosphatase 1 regulatory subunit 21 (Coiled-coil domain-containing protein 128) (Ferry endosomal RAB5 effector complex subunit 2) (Fy-2) (KLRAQ motif-containing protein 1) | Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary) (PubMed:37267905, PubMed:37267906). The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction (PubMed:37267905). In the complex, PPP1R21 serves as a binding hub connecting all five complex subunits and mediating the binding to mRNA and early endosomes via RAB5A (PubMed:37267906). Putative regulator of protein phosphatase 1 (PP1) activity (PubMed:19389623). May play a role in the endosomal sorting process or in endosome maturation pathway (Probable) (PubMed:30520571). {ECO:0000269|PubMed:30520571, ECO:0000269|PubMed:37267905, ECO:0000269|PubMed:37267906, ECO:0000305|PubMed:19389623}. |
| Q6ZN55 | ZNF574 | T147 | ochoa | Zinc finger protein 574 | May be involved in transcriptional regulation. |
| Q6ZNC4 | ZNF704 | T304 | ochoa | Zinc finger protein 704 | Transcription factor which binds to RE2 sequence elements in the MYOD1 enhancer. {ECO:0000250|UniProtKB:Q9ERQ3}. |
| Q6ZS17 | RIPOR1 | T1129 | ochoa | Rho family-interacting cell polarization regulator 1 | Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration (PubMed:27807006). Acts as an adapter protein, linking active Rho proteins to STK24 and STK26 kinases, and hence positively regulates Golgi reorientation in polarized cell migration upon Rho activation (PubMed:27807006). Involved in the subcellular relocation of STK26 from the Golgi to cytoplasm punctae in a Rho- and PDCD10-dependent manner upon serum stimulation (PubMed:27807006). {ECO:0000269|PubMed:27807006}. |
| Q70CQ2 | USP34 | T3385 | ochoa | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| Q70J99 | UNC13D | T628 | ochoa | Protein unc-13 homolog D (Munc13-4) | Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells. {ECO:0000269|PubMed:15548590, ECO:0000269|PubMed:17237785}. |
| Q7L4E1 | MIGA2 | T273 | ochoa | Mitoguardin 2 (Protein FAM73B) | Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD. {ECO:0000269|PubMed:26711011}. |
| Q7L7X3 | TAOK1 | T643 | psp | Serine/threonine-protein kinase TAO1 (EC 2.7.11.1) (Kinase from chicken homolog B) (hKFC-B) (MARK Kinase) (MARKK) (Prostate-derived sterile 20-like kinase 2) (PSK-2) (PSK2) (Prostate-derived STE20-like kinase 2) (Thousand and one amino acid protein kinase 1) (TAOK1) (hTAOK1) | Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system (PubMed:33565190). Also plays a role in the regulation of neuronal migration to the cortical plate (By similarity). {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936, ECO:0000269|PubMed:33565190}. |
| Q7L8J4 | SH3BP5L | T340 | ochoa | SH3 domain-binding protein 5-like (SH3BP-5-like) | Functions as a guanine nucleotide exchange factor (GEF) for RAB11A. {ECO:0000269|PubMed:30217979}. |
| Q7RTP6 | MICAL3 | T508 | ochoa | [F-actin]-monooxygenase MICAL3 (EC 1.14.13.225) (Molecule interacting with CasL protein 3) (MICAL-3) | Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission. {ECO:0000269|PubMed:21596566, ECO:0000269|PubMed:24440334}. |
| Q7Z3B4 | NUP54 | T286 | ochoa | Nucleoporin p54 (54 kDa nucleoporin) | Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane. {ECO:0000250|UniProtKB:P70582}. |
| Q7Z417 | NUFIP2 | T585 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z417 | NUFIP2 | T606 | ochoa | FMR1-interacting protein NUFIP2 (82 kDa FMRP-interacting protein) (82-FIP) (Cell proliferation-inducing gene 1 protein) (FMRP-interacting protein 2) (Nuclear FMR1-interacting protein 2) | Binds RNA. {ECO:0000269|PubMed:12837692}. |
| Q7Z591 | AKNA | T950 | ochoa | Microtubule organization protein AKNA (AT-hook-containing transcription factor) | Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (By similarity). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (By similarity). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (By similarity). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (By similarity). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (PubMed:11268217). Binds to A/T-rich promoters (PubMed:11268217). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable). {ECO:0000250|UniProtKB:Q80VW7, ECO:0000269|PubMed:11268217, ECO:0000305}. |
| Q7Z6Z7 | HUWE1 | T1344 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q86T23 | CROCCP2 | T28 | ochoa | Putative ciliary rootlet coiled-coil protein-like 1 protein (Ciliary rootlet coiled-coil protein pseudogene 2) | None |
| Q86U86 | PBRM1 | T43 | ochoa | Protein polybromo-1 (hPB1) (BRG1-associated factor 180) (BAF180) (Polybromo-1D) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation. {ECO:0000269|PubMed:21248752, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q86UP2 | KTN1 | T232 | ochoa | Kinectin (CG-1 antigen) (Kinesin receptor) | Receptor for kinesin thus involved in kinesin-driven vesicle motility. Accumulates in integrin-based adhesion complexes (IAC) upon integrin aggregation by fibronectin. |
| Q86UP3 | ZFHX4 | T2808 | ochoa | Zinc finger homeobox protein 4 (Zinc finger homeodomain protein 4) (ZFH-4) | May play a role in neural and muscle differentiation (By similarity). May be involved in transcriptional regulation. {ECO:0000250}. |
| Q86UU1 | PHLDB1 | T1015 | ochoa | Pleckstrin homology-like domain family B member 1 (Protein LL5-alpha) | None |
| Q86V15 | CASZ1 | T715 | ochoa | Zinc finger protein castor homolog 1 (Castor-related protein) (Putative survival-related protein) (Zinc finger protein 693) | Transcriptional activator (PubMed:23639441, PubMed:27693370). Involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7 (PubMed:23639441). {ECO:0000269|PubMed:23639441, ECO:0000269|PubMed:27693370}. |
| Q86WJ1 | CHD1L | T629 | ochoa | Chromodomain-helicase-DNA-binding protein 1-like (EC 3.6.4.-) (Amplified in liver cancer protein 1) | ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:33357431, PubMed:34210977, PubMed:34486521, PubMed:34874266). Recruited to DNA damage sites through interaction with poly-ADP-ribose: specifically recognizes and binds histones that are poly-ADP-ribosylated on serine residues in response to DNA damage (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:34486521, PubMed:34874266). Poly-ADP-ribose-binding activates the ATP-dependent chromatin remodeler activity, thereby regulating chromatin during DNA repair (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:34486521, PubMed:34874266). Catalyzes nucleosome sliding away from DNA breaks in an ATP-dependent manner (PubMed:19661379, PubMed:29220652, PubMed:29220653). Chromatin remodeling activity promotes PARP2 removal from chromatin (PubMed:33275888). {ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:29220652, ECO:0000269|PubMed:29220653, ECO:0000269|PubMed:33275888, ECO:0000269|PubMed:33357431, ECO:0000269|PubMed:34210977, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34874266}. |
| Q86YS7 | C2CD5 | T807 | ochoa | C2 domain-containing protein 5 (C2 domain-containing phosphoprotein of 138 kDa) | Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM. {ECO:0000269|PubMed:21907143}. |
| Q8IUG5 | MYO18B | T1548 | ochoa | Unconventional myosin-XVIIIb | May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. May play a role in the control of tumor development and progression; restored MYO18B expression in lung cancer cells suppresses anchorage-independent growth. |
| Q8IUQ4 | SIAH1 | T239 | psp | E3 ubiquitin-protein ligase SIAH1 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase SIAH1) (Seven in absentia homolog 1) (Siah-1) (Siah-1a) | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:28546513, PubMed:32430360, PubMed:33591310, PubMed:9334332, PubMed:9858595). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443). Confers constitutive instability to HIPK2 through proteasomal degradation (PubMed:18536714, PubMed:33591310). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Has some overlapping function with SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (PubMed:28546513, PubMed:32430360). {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}. |
| Q8IW35 | CEP97 | T542 | ochoa | Centrosomal protein of 97 kDa (Cep97) (Leucine-rich repeat and IQ domain-containing protein 2) | Acts as a key negative regulator of ciliogenesis in collaboration with CCP110 by capping the mother centriole thereby preventing cilia formation (PubMed:17719545, PubMed:30375385). Required for recruitment of CCP110 to the centrosome (PubMed:17719545). {ECO:0000269|PubMed:17719545, ECO:0000269|PubMed:30375385}. |
| Q8IWB6 | TEX14 | T727 | psp | Inactive serine/threonine-protein kinase TEX14 (Protein kinase-like protein SgK307) (Sugen kinase 307) (Testis-expressed sequence 14) (Testis-expressed sequence 14 protein) | Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis and male fertility. Acts by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55: interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transform midbodies into intercellular bridges. Also plays a role during mitosis: recruited to kinetochores by PLK1 during early mitosis and regulates the maturation of the outer kinetochores and microtubule attachment. Has no protein kinase activity in vitro (By similarity). {ECO:0000250}. |
| Q8IWJ2 | GCC2 | T1480 | ochoa | GRIP and coiled-coil domain-containing protein 2 (185 kDa Golgi coiled-coil protein) (GCC185) (CLL-associated antigen KW-11) (CTCL tumor antigen se1-1) (Ran-binding protein 2-like 4) (RanBP2L4) (Renal carcinoma antigen NY-REN-53) | Golgin which probably tethers transport vesicles to the trans-Golgi network (TGN) and regulates vesicular transport between the endosomes and the Golgi. As a RAB9A effector it is involved in recycling of the mannose 6-phosphate receptor from the late endosomes to the TGN. May also play a role in transport between the recycling endosomes and the Golgi. Required for maintenance of the Golgi structure, it is involved in the biogenesis of noncentrosomal, Golgi-associated microtubules through recruitment of CLASP1 and CLASP2. {ECO:0000269|PubMed:16885419, ECO:0000269|PubMed:17488291, ECO:0000269|PubMed:17543864}. |
| Q8IWZ8 | SUGP1 | T132 | ochoa | SURP and G-patch domain-containing protein 1 (RNA-binding protein RBP) (Splicing factor 4) | Plays a role in pre-mRNA splicing. |
| Q8IX12 | CCAR1 | T667 | psp | Cell division cycle and apoptosis regulator protein 1 (Cell cycle and apoptosis regulatory protein 1) (CARP-1) (Death inducer with SAP domain) | Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation (By similarity). May be involved in apoptosis signaling in the presence of the reinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation (PubMed:12816952). In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells (PubMed:23887938). {ECO:0000250|UniProtKB:Q8CH18, ECO:0000269|PubMed:12816952, ECO:0000269|PubMed:23887938, ECO:0000269|PubMed:24245781}. |
| Q8IZ21 | PHACTR4 | T632 | ochoa | Phosphatase and actin regulator 4 | Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway (By similarity). {ECO:0000250}. |
| Q8IZH2 | XRN1 | T753 | ochoa | 5'-3' exoribonuclease 1 (EC 3.1.13.-) (Strand-exchange protein 1 homolog) | Major 5'-3' exoribonuclease involved in mRNA decay. Required for the 5'-3'-processing of the G4 tetraplex-containing DNA and RNA substrates. The kinetic of hydrolysis is faster for G4 RNA tetraplex than for G4 DNA tetraplex and monomeric RNA tetraplex. Binds to RNA and DNA (By similarity). Plays a role in replication-dependent histone mRNA degradation. May act as a tumor suppressor protein in osteogenic sarcoma (OGS). {ECO:0000250|UniProtKB:P97789, ECO:0000269|PubMed:18172165}. |
| Q8N3J3 | HROB | T377 | ochoa | Homologous recombination OB-fold protein | DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis. {ECO:0000269|PubMed:31467087}. |
| Q8N4C8 | MINK1 | T809 | ochoa | Misshapen-like kinase 1 (EC 2.7.11.1) (GCK family kinase MiNK) (MAPK/ERK kinase kinase kinase 6) (MEK kinase kinase 6) (MEKKK 6) (Misshapen/NIK-related kinase) (Mitogen-activated protein kinase kinase kinase kinase 6) | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking (PubMed:10708748, PubMed:16337592). Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons (By similarity). Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1 (PubMed:18930710, PubMed:21690388). Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1 (By similarity). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000250|UniProtKB:F1LP90, ECO:0000250|UniProtKB:Q9JM52, ECO:0000269|PubMed:10708748, ECO:0000269|PubMed:16337592, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. |
| Q8N5A5 | ZGPAT | T271 | ochoa | Zinc finger CCCH-type with G patch domain-containing protein (G patch domain-containing protein 6) (Zinc finger CCCH domain-containing protein 9) (Zinc finger and G patch domain-containing protein) | Transcription repressor that specifically binds the 5'-GGAG[GA]A[GA]A-3' consensus sequence. Represses transcription by recruiting the chromatin multiprotein complex NuRD to target promoters. Negatively regulates expression of EGFR, a gene involved in cell proliferation, survival and migration. Its ability to repress genes of the EGFR pathway suggest it may act as a tumor suppressor. Able to suppress breast carcinogenesis. {ECO:0000269|PubMed:19644445}.; FUNCTION: [Isoform 4]: Antagonizes the transcription repression by isoform 1 by competing for the binding of the NuRD complex. Does not bind DNA. {ECO:0000269|PubMed:19644445}. |
| Q8NB14 | USP38 | T677 | ochoa | Ubiquitin carboxyl-terminal hydrolase 38 (EC 3.4.19.12) (Deubiquitinating enzyme 38) (HP43.8KD) (Ubiquitin thioesterase 38) (Ubiquitin-specific-processing protease 38) | Deubiquitinating enzyme that plays a role in various cellular processes, including DNA repair, cell cycle regulation, and immune response (PubMed:22689415, PubMed:30497519, PubMed:31874856, PubMed:35238669). Plays a role in the inhibition of type I interferon signaling by mediating the 'Lys-33' to 'Lys-48' ubiquitination transition of TBK1 leading to its degradation (PubMed:27692986). Cleaves the ubiquitin chain from the histone demethylase LSD1/KDM1A and prevents it from degradation by the 26S proteasome, thus maintaining LSD1 protein level in cells (PubMed:30497519). Plays a role in the DNA damage response by regulating the deacetylase activity of HDAC1 (PubMed:31874856). Mechanistically, removes the 'Lys-63'-linked ubiquitin chain promoting the deacetylase activity of HDAC1 in response to DNA damage (PubMed:31874856). Also acts as a specific deubiquitinase of histone deacetylase 3/HDAC3 and cleaves its 'Lys-63'-linked ubiquitin chains to lower its histone deacetylase activity (PubMed:32404892). Regulates MYC levels and cell proliferation via antagonizing ubiquitin E3 ligase FBXW7 thereby preventing MYC 'Lys-48'-linked ubiquitination and degradation (PubMed:34102342). Participates in antiviral response by removing both 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of Zika virus envelope protein E (PubMed:34696459). Constitutively associated with IL-33R/IL1RL1, deconjugates its 'Lys-27'-linked polyubiquitination resulting in its autophagic degradation (PubMed:35238669). {ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:27692986, ECO:0000269|PubMed:30497519, ECO:0000269|PubMed:31874856, ECO:0000269|PubMed:32404892, ECO:0000269|PubMed:34102342, ECO:0000269|PubMed:34696459, ECO:0000269|PubMed:35238669}. |
| Q8ND76 | CCNY | T37 | ochoa | Cyclin-Y (Cyc-Y) (Cyclin box protein 1) (Cyclin fold protein 1) (cyclin-X) | Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6, leading to the activation of the Wnt signaling pathway. Recruits CDK16 to the plasma membrane. Isoform 3 might play a role in the activation of MYC-mediated transcription. {ECO:0000269|PubMed:18060517, ECO:0000269|PubMed:19524571, ECO:0000269|PubMed:20059949, ECO:0000269|PubMed:22184064}. |
| Q8NE01 | CNNM3 | T683 | ochoa | Metal transporter CNNM3 (Ancient conserved domain-containing protein 3) (Cyclin-M3) | Probable metal transporter. {ECO:0000250}. |
| Q8NEG4 | FAM83F | T317 | ochoa | Protein FAM83F | None |
| Q8NEM2 | SHCBP1 | T623 | ochoa | SHC SH2 domain-binding protein 1 | May play a role in signaling pathways governing cellular proliferation, cell growth and differentiation. May be a component of a novel signaling pathway downstream of Shc. Acts as a positive regulator of FGF signaling in neural progenitor cells. {ECO:0000250|UniProtKB:Q9Z179}. |
| Q8NEV4 | MYO3A | T302 | psp | Myosin-IIIa (EC 2.7.11.1) | Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:29880844, PubMed:34788109). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315, ECO:0000269|PubMed:29880844, ECO:0000269|PubMed:34788109}. |
| Q8NEV4 | MYO3A | T908 | psp | Myosin-IIIa (EC 2.7.11.1) | Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:29880844, PubMed:34788109). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315, ECO:0000269|PubMed:29880844, ECO:0000269|PubMed:34788109}. |
| Q8NEY1 | NAV1 | T534 | ochoa | Neuron navigator 1 (Pore membrane and/or filament-interacting-like protein 3) (Steerin-1) (Unc-53 homolog 1) (unc53H1) | May be involved in neuronal migration. {ECO:0000250}. |
| Q8NFC6 | BOD1L1 | T1308 | ochoa | Biorientation of chromosomes in cell division protein 1-like 1 | Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}. |
| Q8NGS8 | OR13C5 | T110 | ochoa | Olfactory receptor 13C5 (Olfactory receptor OR9-11) | Odorant receptor. {ECO:0000305}. |
| Q8NI77 | KIF18A | T681 | ochoa | Kinesin-like protein KIF18A (Marrow stromal KIF18A) (MS-KIF18A) | Microtubule-depolymerizing kinesin which plays a role in chromosome congression by reducing the amplitude of preanaphase oscillations and slowing poleward movement during anaphase, thus suppressing chromosome movements. May stabilize the CENPE-BUB1B complex at the kinetochores during early mitosis and maintains CENPE levels at kinetochores during chromosome congression. {ECO:0000269|PubMed:17346968, ECO:0000269|PubMed:18267093, ECO:0000269|PubMed:18513970, ECO:0000269|PubMed:19625775}. |
| Q8TEW0 | PARD3 | T895 | ochoa | Partitioning defective 3 homolog (PAR-3) (PARD-3) (Atypical PKC isotype-specific-interacting protein) (ASIP) (CTCL tumor antigen se2-5) (PAR3-alpha) | Adapter protein involved in asymmetrical cell division and cell polarization processes (PubMed:10954424, PubMed:27925688). Seems to play a central role in the formation of epithelial tight junctions (PubMed:27925688). Targets the phosphatase PTEN to cell junctions (By similarity). Involved in Schwann cell peripheral myelination (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (By similarity). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10934474). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (PubMed:19812038, PubMed:27925688). {ECO:0000250|UniProtKB:Q99NH2, ECO:0000250|UniProtKB:Q9Z340, ECO:0000269|PubMed:10934474, ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:27925688}. |
| Q8WUA4 | GTF3C2 | T370 | ochoa | General transcription factor 3C polypeptide 2 (TF3C-beta) (Transcription factor IIIC 110 kDa subunit) (TFIIIC 110 kDa subunit) (TFIIIC110) (Transcription factor IIIC subunit beta) | Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. May play a direct role in stabilizing interactions of TFIIIC2 with TFIIIC1. |
| Q8WWH5 | TRUB1 | T27 | ochoa | Pseudouridylate synthase TRUB1 (EC 5.4.99.-) (TruB pseudouridine synthase homolog 1) (tRNA pseudouridine 55 synthase TRUB1) (Psi55 synthase TRUB1) (EC 5.4.99.25) | Pseudouridine synthase that catalyzes pseudouridylation of mRNAs and tRNAs (PubMed:28073919, PubMed:31477916, PubMed:32926445). Mediates pseudouridylation of mRNAs with the consensus sequence 5'-GUUCNANNC-3', harboring a stem-loop structure (PubMed:28073919, PubMed:31477916). Constitutes the major pseudouridine synthase acting on mRNAs (PubMed:28073919). Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs (PubMed:32926445, PubMed:33023933). Promotes the processing of pri-let-7 microRNAs (pri-miRNAs) independently of its RNA pseudouridylate synthase activity (PubMed:32926445). Acts by binding to the stem-loop structure on pri-let-7, preventing LIN28-binding (LIN28A and/or LIN28B), thereby enhancing the interaction between pri-let-7 and the microprocessor DGCR8, which mediates miRNA maturation (PubMed:32926445). {ECO:0000269|PubMed:28073919, ECO:0000269|PubMed:31477916, ECO:0000269|PubMed:32926445, ECO:0000269|PubMed:33023933}. |
| Q8WWI1 | LMO7 | T932 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWN8 | ARAP3 | T1369 | ochoa | Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (Centaurin-delta-3) (Cnt-d3) | Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin. {ECO:0000269|PubMed:11804589, ECO:0000269|PubMed:15569923}. |
| Q8WXE0 | CASKIN2 | T252 | ochoa | Caskin-2 (CASK-interacting protein 2) | None |
| Q8WXE0 | CASKIN2 | T989 | ochoa | Caskin-2 (CASK-interacting protein 2) | None |
| Q8WXE1 | ATRIP | T65 | ochoa | ATR-interacting protein (ATM and Rad3-related-interacting protein) | Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein. {ECO:0000269|PubMed:12791985}. |
| Q92619 | ARHGAP45 | T944 | 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}. |
| Q92844 | TANK | T68 | ochoa | TRAF family member-associated NF-kappa-B activator (TRAF-interacting protein) (I-TRAF) | Adapter protein involved in I-kappa-B-kinase (IKK) regulation which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity. Acts as a regulator of TRAF function by maintaining them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. Negatively regulates NF-kappaB signaling and cell survival upon DNA damage (PubMed:25861989). Plays a role as an adapter to assemble ZC3H12A, USP10 in a deubiquitination complex which plays a negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Promotes UBP10-induced deubiquitination of TRAF6 in response to DNA damage (PubMed:25861989). May control negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2. {ECO:0000269|PubMed:12133833, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:25861989}. |
| Q969P6 | TOP1MT | T405 | ochoa | DNA topoisomerase I, mitochondrial (TOP1mt) (EC 5.6.2.1) | Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). {ECO:0000250, ECO:0000269|PubMed:11526219}. |
| Q96AC1 | FERMT2 | T362 | ochoa | Fermitin family homolog 2 (Kindlin-2) (Mitogen-inducible gene 2 protein) (MIG-2) (Pleckstrin homology domain-containing family C member 1) (PH domain-containing family C member 1) | Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling. {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155, ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}. |
| Q96DX8 | RTP4 | T183 | ochoa | Receptor-transporting protein 4 (28 kDa interferon-responsive protein) (3CxxC-type zinc finger protein 4) | Chaperone protein that facilitates the trafficking and functional cell surface expression of some G-protein coupled receptors (GPCRs) (PubMed:18836069). Promotes functional expression of the bitter taste receptor TAS2R16 (PubMed:16720576). Also promotes functional expression of the opioid receptor heterodimer OPRD1-OPRM1 (By similarity). In addition, acts as a potent IFN-inducible suppressor of pathogens including lyssavirus rabies, influenza A or yellow fever virus (PubMed:33113352). Mechanistically, associates with the viral replicase, binds viral RNA, and thereby suppresses viral genome amplification that replicates at the endoplasmic reticulum (By similarity). In addition, restores antiviral signaling by interacting with and sequestering influenza A virus protein NS1 (PubMed:39798334). {ECO:0000250|UniProtKB:Q9ER80, ECO:0000269|PubMed:16720576, ECO:0000269|PubMed:18836069, ECO:0000269|PubMed:33113352, ECO:0000269|PubMed:39798334}. |
| Q96FA3 | PELI1 | T86 | psp | E3 ubiquitin-protein ligase pellino homolog 1 (Pellino-1) (EC 2.3.2.27) (Pellino-related intracellular-signaling molecule) (RING-type E3 ubiquitin transferase pellino homolog 1) | E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:12496252, PubMed:17675297, PubMed:29883609, PubMed:30952868). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6 (PubMed:12496252, PubMed:17675297). Acts as a positive regulator of inflammatory response in microglia through activation of NF-kappa-B and MAP kinase (By similarity). Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation (PubMed:12496252, PubMed:17675297). Conjugates 'Lys-63'-linked ubiquitin chains to the adapter protein ASC/PYCARD, which in turn is crucial for NLRP3 inflammasome activation (PubMed:34706239). Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates 'Lys-63'-linked ubiquitination of RIPK1 (PubMed:29883609). Following phosphorylation by ATM, catalyzes 'Lys-63'-linked ubiquitination of NBN, promoting DNA repair via homologous recombination (PubMed:30952868). Negatively regulates activation of the metabolic mTORC1 signaling pathway by mediating 'Lys-63'-linked ubiquitination of mTORC1-inhibitory protein TSC1 and thereby promoting TSC1/TSC2 complex stability (PubMed:33215753). {ECO:0000250|UniProtKB:Q8C669, ECO:0000269|PubMed:12496252, ECO:0000269|PubMed:17675297, ECO:0000269|PubMed:29883609, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:33215753}. |
| Q96I24 | FUBP3 | T76 | 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. |
| Q96L73 | NSD1 | T563 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-36 specific (EC 2.1.1.357) (Androgen receptor coactivator 267 kDa protein) (Androgen receptor-associated protein of 267 kDa) (H3-K36-HMTase) (Lysine N-methyltransferase 3B) (Nuclear receptor-binding SET domain-containing protein 1) (NR-binding SET domain-containing protein) | Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. |
| Q96PC5 | MIA2 | T1118 | ochoa | Melanoma inhibitory activity protein 2 (MIA protein 2) (CTAGE family member 5 ER export factor) (Cutaneous T-cell lymphoma-associated antigen 5) (Meningioma-expressed antigen 6/11) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum (PubMed:21525241, PubMed:25202031, PubMed:27138255, PubMed:27170179). Plays a role in the secretion of lipoproteins, pre-chylomicrons and pre-VLDLs, by participating in their export from the endoplasmic reticulum (PubMed:27138255). Thereby, may play a role in cholesterol and triglyceride homeostasis (By similarity). Required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers and recruiting PREB/SEC12 at the endoplasmic reticulum exit sites (PubMed:21525241, PubMed:25202031, PubMed:27170179). {ECO:0000250|UniProtKB:Q91ZV0, ECO:0000269|PubMed:21525241, ECO:0000269|PubMed:25202031, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:27170179}. |
| Q96PM5 | RCHY1 | T154 | psp | RING finger and CHY zinc finger domain-containing protein 1 (EC 2.3.2.27) (Androgen receptor N-terminal-interacting protein) (CH-rich-interacting match with PLAG1) (E3 ubiquitin-protein ligase Pirh2) (RING finger protein 199) (RING-type E3 ubiquitin transferase RCHY1) (Zinc finger protein 363) (p53-induced RING-H2 protein) (hPirh2) | E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins, including p53/TP53, TP73, HDAC1 and CDKN1B (PubMed:16914734, PubMed:17721809, PubMed:18006823, PubMed:19043414, PubMed:19483087, PubMed:21994467). Mediates ubiquitination and degradation of p53/TP53; preferentially acts on tetrameric p53/TP53 (PubMed:19043414, PubMed:19483087). Catalyzes monoubiquitinates the translesion DNA polymerase POLH (PubMed:21791603). Involved in the ribosome-associated quality control (RQC) pathway, which mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes: RCHY1 acts downstream of NEMF and recognizes CAT tails associated with stalled nascent chains, leading to their ubiquitination and degradation (PubMed:33909987). {ECO:0000269|PubMed:16914734, ECO:0000269|PubMed:17721809, ECO:0000269|PubMed:18006823, ECO:0000269|PubMed:19043414, ECO:0000269|PubMed:19483087, ECO:0000269|PubMed:21791603, ECO:0000269|PubMed:21994467, ECO:0000269|PubMed:33909987}.; FUNCTION: [Isoform 4]: Has no E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20452352}. |
| Q96PN7 | TRERF1 | T702 | ochoa | Transcriptional-regulating factor 1 (Breast cancer anti-estrogen resistance 2) (Transcriptional-regulating protein 132) (Zinc finger protein rapa) (Zinc finger transcription factor TReP-132) | Binds DNA and activates transcription of CYP11A1. Interaction with CREBBP and EP300 results in a synergistic transcriptional activation of CYP11A1. {ECO:0000269|PubMed:11349124, ECO:0000269|PubMed:16371131}. |
| Q96PU5 | NEDD4L | T903 | psp | E3 ubiquitin-protein ligase NEDD4-like (EC 2.3.2.26) (EC 2.3.2.36) (HECT-type E3 ubiquitin transferase NED4L) (NEDD4.2) (Nedd4-2) | E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins and is thereby implicated in the regulation of various signaling pathways including autophagy, innate immunity or DNA repair (PubMed:20064473, PubMed:31959741, PubMed:33608556). Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation (PubMed:15496141). Downregulates autophagy and cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2 levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). Plays a role in antiviral innate immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked ubiquitination of TRAF3 (PubMed:33608556). Ubiquitinates TTYH2 and TTYH3 and regulates protein levels of TTYH2 (PubMed:18577513). {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:18577513, ECO:0000269|PubMed:19144635, ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27694961, ECO:0000269|PubMed:33608556}. |
| Q96PY6 | NEK1 | T141 | psp | Serine/threonine-protein kinase Nek1 (EC 2.7.11.1) (Never in mitosis A-related kinase 1) (NimA-related protein kinase 1) (Renal carcinoma antigen NY-REN-55) | Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:20230784). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:20230784). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (PubMed:20230784). May be implicated in the control of meiosis (By similarity). Involved in cilium assembly (PubMed:21211617). {ECO:0000250|UniProtKB:P51954, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:21211617}. |
| Q96QT4 | TRPM7 | T1467 | ochoa | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96RG2 | PASK | T62 | ochoa | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96T23 | RSF1 | T1388 | ochoa | Remodeling and spacing factor 1 (Rsf-1) (HBV pX-associated protein 8) (Hepatitis B virus X-associated protein) (p325 subunit of RSF chromatin-remodeling complex) | Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF-alpha induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984). {ECO:0000269|PubMed:11788598, ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:28801535}. |
| Q99614 | TTC1 | T23 | ochoa | Tetratricopeptide repeat protein 1 (TPR repeat protein 1) | None |
| Q99814 | EPAS1 | T324 | psp | Endothelial PAS domain-containing protein 1 (EPAS-1) (Basic-helix-loop-helix-PAS protein MOP2) (Class E basic helix-loop-helix protein 73) (bHLHe73) (HIF-1-alpha-like factor) (HLF) (Hypoxia-inducible factor 2-alpha) (HIF-2-alpha) (HIF2-alpha) (Member of PAS protein 2) (PAS domain-containing protein 2) | Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX1 seems to activate CTAD (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P97481}. |
| Q9BSJ8 | ESYT1 | T959 | ochoa | Extended synaptotagmin-1 (E-Syt1) (Membrane-bound C2 domain-containing protein) | Binds calcium (via the C2 domains) and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels (PubMed:23791178, PubMed:24183667). Helps tether the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane (PubMed:24183667). Acts as an inhibitor of ADGRD1 G-protein-coupled receptor activity in absence of cytosolic calcium (PubMed:38758649). Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity). {ECO:0000250|UniProtKB:A0FGR8, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24183667, ECO:0000269|PubMed:38758649}. |
| Q9BV36 | MLPH | T249 | ochoa | Melanophilin (Exophilin-3) (Slp homolog lacking C2 domains a) (SlaC2-a) (Synaptotagmin-like protein 2a) | Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}. |
| Q9BV36 | MLPH | T313 | ochoa | Melanophilin (Exophilin-3) (Slp homolog lacking C2 domains a) (SlaC2-a) (Synaptotagmin-like protein 2a) | Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. {ECO:0000269|PubMed:12062444}. |
| Q9BW04 | SARG | T471 | ochoa | Specifically androgen-regulated gene protein | Putative androgen-specific receptor. {ECO:0000269|PubMed:15525603}. |
| Q9BXM7 | PINK1 | T313 | psp | Serine/threonine-protein kinase PINK1, mitochondrial (EC 2.7.11.1) (BRPK) (PTEN-induced putative kinase protein 1) | Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. It phosphorylates mitochondrial proteins to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:18957282, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20547144, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:24898855, PubMed:25527291, PubMed:32484300). Depending on the severity of mitochondrial damage, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN-dependent mitophagy (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23933751, PubMed:24898855, PubMed:32047033, PubMed:32484300). When cellular stress results in irreversible mitochondrial damage, PINK1 accumulates at the outer mitochondrial membrane (OMM) where it phosphorylates pre-existing polyubiquitin chains at 'Ser-65', recruits PRKN from the cytosol to the OMM and activates PRKN by phosphorylation at 'Ser-65'; activated PRKN then ubiquinates VDAC1 and other OMM proteins to initiate mitophagy (PubMed:14607334, PubMed:15087508, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291, PubMed:32047033). The PINK1-PRKN pathway also promotes fission of damaged mitochondria through phosphorylation and PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128). {ECO:0000250|UniProtKB:Q99MQ3, ECO:0000269|PubMed:14607334, ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:18443288, ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20547144, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:24898855, ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:29123128, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:32484300}. |
| Q9BXW9 | FANCD2 | T691 | ochoa|psp | Fanconi anemia group D2 protein (Protein FACD2) | Required for maintenance of chromosomal stability (PubMed:11239453, PubMed:14517836). Promotes accurate and efficient pairing of homologs during meiosis (PubMed:14517836). Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing (PubMed:15671039, PubMed:15650050, PubMed:30335751, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (By similarity). May participate in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:15377654). Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (PubMed:15454491, PubMed:15661754). Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress (PubMed:15661754, PubMed:19465921). Promotes BRCA2/FANCD1 loading onto damaged chromatin (PubMed:11239454, PubMed:12239151, PubMed:12086603, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:18212739). May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250|UniProtKB:Q68Y81, ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:36385258}. |
| Q9BY89 | KIAA1671 | T725 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BY89 | KIAA1671 | T778 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYX2 | TBC1D2 | T186 | ochoa | TBC1 domain family member 2A (Armus) (Prostate antigen recognized and identified by SEREX 1) (PARIS-1) | Acts as a GTPase-activating protein for RAB7A. Signal effector acting as a linker between RAC1 and RAB7A, leading to RAB7A inactivation and subsequent inhibition of cadherin degradation and reduced cell-cell adhesion. {ECO:0000269|PubMed:20116244}. |
| Q9BZI7 | UPF3B | T169 | ochoa | Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B) (Up-frameshift suppressor 3 homolog B) (hUpf3B) (Up-frameshift suppressor 3 homolog on chromosome X) (hUpf3p-X) | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF2 stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA upstream of exon-exon junctions. In vitro, stimulates translation; the function is independent of association with UPF2 and components of the EJC core. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:16601204, ECO:0000269|PubMed:18066079}. |
| Q9BZQ8 | NIBAN1 | T717 | ochoa | Protein Niban 1 (Cell growth-inhibiting gene 39 protein) (Protein FAM129A) | Regulates phosphorylation of a number of proteins involved in translation regulation including EIF2A, EIF4EBP1 and RPS6KB1. May be involved in the endoplasmic reticulum stress response (By similarity). {ECO:0000250}. |
| Q9C0D5 | TANC1 | T613 | ochoa | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9GZR1 | SENP6 | T323 | ochoa | Sentrin-specific protease 6 (EC 3.4.22.-) (SUMO-1-specific protease 1) (Sentrin/SUMO-specific protease SENP6) | Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Also desumoylates RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. {ECO:0000269|PubMed:16912044, ECO:0000269|PubMed:17000875, ECO:0000269|PubMed:18799455, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20705237, ECO:0000269|PubMed:21148299}. |
| Q9H0A0 | NAT10 | T686 | ochoa | RNA cytidine acetyltransferase (EC 2.3.1.-) (18S rRNA cytosine acetyltransferase) (N-acetyltransferase 10) (N-acetyltransferase-like protein) (hALP) | RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs (PubMed:25411247, PubMed:25653167, PubMed:30449621, PubMed:35679869). Catalyzes ac4C modification of a broad range of mRNAs, enhancing mRNA stability and translation (PubMed:30449621, PubMed:35679869). mRNA ac4C modification is frequently present within wobble cytidine sites and promotes translation efficiency (PubMed:30449621). Mediates the formation of ac4C at position 1842 in 18S rRNA (PubMed:25411247). May also catalyze the formation of ac4C at position 1337 in 18S rRNA (By similarity). Required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis (PubMed:25411247, PubMed:25653167). Catalyzes the formation of ac4C in serine and leucine tRNAs (By similarity). Requires the tRNA-binding adapter protein THUMPD1 for full tRNA acetyltransferase activity but not for 18S rRNA acetylation (PubMed:25653167). In addition to RNA acetyltransferase activity, also able to acetylate lysine residues of proteins, such as histones, microtubules, p53/TP53 and MDM2, in vitro (PubMed:14592445, PubMed:17631499, PubMed:19303003, PubMed:26882543, PubMed:27993683, PubMed:30165671). The relevance of the protein lysine acetyltransferase activity is however unsure in vivo (PubMed:30449621). Activates telomerase activity by stimulating the transcription of TERT, and may also regulate telomerase function by affecting the balance of telomerase subunit assembly, disassembly, and localization (PubMed:14592445, PubMed:18082603). Involved in the regulation of centrosome duplication by acetylating CENATAC during mitosis, promoting SASS6 proteasome degradation (PubMed:31722219). 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:0000250|UniProtKB:P53914, ECO:0000269|PubMed:14592445, ECO:0000269|PubMed:17631499, ECO:0000269|PubMed:18082603, ECO:0000269|PubMed:19303003, ECO:0000269|PubMed:25411247, ECO:0000269|PubMed:25653167, ECO:0000269|PubMed:26882543, ECO:0000269|PubMed:27993683, ECO:0000269|PubMed:30165671, ECO:0000269|PubMed:30449621, ECO:0000269|PubMed:31722219, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:35679869}. |
| Q9H1Y0 | ATG5 | T101 | psp | Autophagy protein 5 (APG5-like) (Apoptosis-specific protein) | Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway. As part of the ATG8 conjugation system with ATG12 and ATG16L1, required for recruitment of LRRK2 to stressed lysosomes and induction of LRRK2 kinase activity in response to lysosomal stress (By similarity). {ECO:0000250|UniProtKB:Q99J83, ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:20580051, ECO:0000269|PubMed:22170153, ECO:0000269|PubMed:26812546}.; FUNCTION: May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD. {ECO:0000269|PubMed:15778222, ECO:0000269|PubMed:7796880}.; FUNCTION: (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601). {ECO:0000269|PubMed:17709747, ECO:0000269|PubMed:19666601}. |
| Q9H2G2 | SLK | T506 | ochoa | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q9H2J7 | SLC6A15 | T674 | ochoa | Sodium-dependent neutral amino acid transporter B(0)AT2 (Sodium- and chloride-dependent neurotransmitter transporter NTT73) (Sodium-coupled branched-chain amino-acid transporter 1) (Solute carrier family 6 member 15) (Transporter v7-3) | Functions as a sodium-dependent neutral amino acid transporter. Exhibits preference for the branched-chain amino acids, particularly leucine, valine and isoleucine and methionine. Can also transport low-affinity substrates such as alanine, phenylalanine, glutamine and pipecolic acid. Mediates the saturable, pH-sensitive and electrogenic cotransport of proline and sodium ions with a stoichiometry of 1:1. May have a role as transporter for neurotransmitter precursors into neurons. In contrast to other members of the neurotransmitter transporter family, does not appear to be chloride-dependent. {ECO:0000269|PubMed:16226721}. |
| Q9H2Y7 | ZNF106 | T672 | ochoa | Zinc finger protein 106 (Zfp-106) (Zinc finger protein 474) | RNA-binding protein. Specifically binds to 5'-GGGGCC-3' sequence repeats in RNA. Essential for maintenance of peripheral motor neuron and skeletal muscle function. Required for normal expression and/or alternative splicing of a number of genes in spinal cord and skeletal muscle, including the neurite outgrowth inhibitor RTN4. Also contributes to normal mitochondrial respiratory function in motor neurons, via an unknown mechanism. {ECO:0000250|UniProtKB:O88466}. |
| Q9H3R2 | MUC13 | T472 | ochoa | Mucin-13 (MUC-13) (Down-regulated in colon cancer 1) | Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling. |
| Q9H444 | CHMP4B | T101 | ochoa | Charged multivesicular body protein 4b (Chromatin-modifying protein 4b) (CHMP4b) (SNF7 homolog associated with Alix 1) (SNF7-2) (hSnf7-2) (Vacuolar protein sorting-associated protein 32-2) (Vps32-2) (hVps32-2) | Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (PubMed:12860994, PubMed:18209100). 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). Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). Majority of the protein exists in a folded closed conformation (PubMed:33349255). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:33349255}.; FUNCTION: (Microbial infection) The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:22422861}. |
| Q9H497 | TOR3A | T362 | ochoa | Torsin-3A (ATP-dependent interferon-responsive protein) (Torsin family 3 member A) | None |
| Q9H5I5 | PIEZO2 | T1879 | ochoa | Piezo-type mechanosensitive ion channel component 2 (Protein FAM38B) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). {ECO:0000250|UniProtKB:Q8CD54, ECO:0000269|PubMed:33057202, ECO:0000269|PubMed:37590348}. |
| Q9H792 | PEAK1 | T476 | ochoa | Inactive tyrosine-protein kinase PEAK1 (Pseudopodium-enriched atypical kinase 1) (Sugen kinase 269) (Tyrosine-protein kinase SgK269) | Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics (PubMed:20534451, PubMed:23105102, PubMed:35687021). Acts as a scaffold for mediating EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654, ECO:0000269|PubMed:35687021}. |
| Q9HAW4 | CLSPN | T916 | psp | Claspin (hClaspin) | Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| Q9HB90 | RRAGC | T96 | ochoa | Ras-related GTP-binding protein C (Rag C) (RagC) (EC 3.6.5.-) (GTPase-interacting protein 2) (TIB929) | Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:27234373, PubMed:31601708, PubMed:31601764, PubMed:32612235, PubMed:34071043, PubMed:36697823, PubMed:37057673). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagC/RRAGC is in its active form when GDP-bound RagC/RRAGC forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagC/RRAGC heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279, PubMed:31601708, PubMed:31601764, PubMed:32868926). In its GDP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279, PubMed:27234373, PubMed:32612235, PubMed:36697823). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279, PubMed:27234373). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagC/RRAGC mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235, PubMed:36697823). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:27234373, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31601764, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32868926, ECO:0000269|PubMed:34071043, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37057673}. |
| Q9HBA0 | TRPV4 | T175 | psp | Transient receptor potential cation channel subfamily V member 4 (TrpV4) (Osm-9-like TRP channel 4) (OTRPC4) (Transient receptor potential protein 12) (TRP12) (Vanilloid receptor-like channel 2) (Vanilloid receptor-like protein 2) (VRL-2) (Vanilloid receptor-related osmotically-activated channel) (VR-OAC) | Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:22526352, PubMed:23136043, PubMed:29899501). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18695040, PubMed:18826956, PubMed:29899501). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:20037586, PubMed:21964574, PubMed:25256292). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (PubMed:29899501). In neurons of the central nervous system, could play a role in triggering voluntary water intake in response to increased sodium concentration in body fluid (By similarity). {ECO:0000250|UniProtKB:Q9EPK8, ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:18587396, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956, ECO:0000269|PubMed:19759329, ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:23136043, ECO:0000269|PubMed:25256292, ECO:0000269|PubMed:26249260, ECO:0000269|PubMed:29899501}.; FUNCTION: [Isoform 1]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 5]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 2]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 4]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 6]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}. |
| Q9HCE1 | MOV10 | T160 | ochoa | Helicase MOV-10 (EC 3.6.4.13) (Armitage homolog) (Moloney leukemia virus 10 protein) | 5' to 3' RNA helicase that is involved in a number of cellular roles ranging from mRNA metabolism and translation, modulation of viral infectivity, inhibition of retrotransposition, or regulation of synaptic transmission (PubMed:23093941). Plays an important role in innate antiviral immunity by promoting type I interferon production (PubMed:27016603, PubMed:27974568, PubMed:35157734). Mechanistically, specifically uses IKKepsilon/IKBKE as the mediator kinase for IRF3 activation (PubMed:27016603, PubMed:35157734). Blocks HIV-1 virus replication at a post-entry step (PubMed:20215113). Counteracts HIV-1 Vif-mediated degradation of APOBEC3G through its helicase activity by interfering with the ubiquitin-proteasome pathway (PubMed:29258557). Also inhibits hepatitis B virus/HBV replication by interacting with HBV RNA and thereby inhibiting the early step of viral reverse transcription (PubMed:31722967). Contributes to UPF1 mRNA target degradation by translocation along 3' UTRs (PubMed:24726324). Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:16289642, PubMed:17507929, PubMed:22791714). In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2 (PubMed:25464849). Restricts retrotransposition of long interspersed element-1 (LINE-1) in cooperation with TUT4 and TUT7 counteracting the RNA chaperonne activity of L1RE1 (PubMed:23093941, PubMed:30122351). Facilitates LINE-1 uridylation by TUT4 and TUT7 (PubMed:30122351). Required for embryonic viability and for normal central nervous system development and function. Plays two critical roles in early brain development: suppresses retroelements in the nucleus by directly inhibiting cDNA synthesis, while regulates cytoskeletal mRNAs to influence neurite outgrowth in the cytosol (By similarity). May function as a messenger ribonucleoprotein (mRNP) clearance factor (PubMed:24726324). {ECO:0000250|UniProtKB:P23249, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:17507929, ECO:0000269|PubMed:20215113, ECO:0000269|PubMed:22791714, ECO:0000269|PubMed:23093941, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:27016603, ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:29258557, ECO:0000269|PubMed:30122351, ECO:0000269|PubMed:31722967, ECO:0000269|PubMed:35157734}.; FUNCTION: (Microbial infection) Required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription. {ECO:0000269|PubMed:18552826}. |
| Q9NP58 | ABCB6 | T754 | ochoa | ATP-binding cassette sub-family B member 6 (ABC-type heme transporter ABCB6) (EC 7.6.2.5) (Mitochondrial ABC transporter 3) (Mt-ABC transporter 3) (P-glycoprotein-related protein) (Ubiquitously-expressed mammalian ABC half transporter) | ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:17661442, PubMed:23792964, PubMed:27507172, PubMed:33007128). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:10837493, PubMed:17006453, PubMed:23792964, PubMed:33007128). May also play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils (PubMed:29940187). In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin (PubMed:21266531, PubMed:25202056, PubMed:31053883). In addition may play a role in the transition metal homeostasis (By similarity). {ECO:0000250|UniProtKB:O70595, ECO:0000269|PubMed:10837493, ECO:0000269|PubMed:17006453, ECO:0000269|PubMed:17661442, ECO:0000269|PubMed:21266531, ECO:0000269|PubMed:23792964, ECO:0000269|PubMed:25202056, ECO:0000269|PubMed:27507172, ECO:0000269|PubMed:29940187, ECO:0000269|PubMed:31053883, ECO:0000269|PubMed:33007128}. |
| Q9NP97 | DYNLRB1 | T56 | ochoa | Dynein light chain roadblock-type 1 (Bithoraxoid-like protein) (BLP) (Dynein light chain 2A, cytoplasmic) (Dynein-associated protein Km23) (Roadblock domain-containing protein 1) | Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. {ECO:0000305|PubMed:36071160}. |
| Q9NQ75 | CASS4 | T225 | ochoa | Cas scaffolding protein family member 4 (HEF-like protein) (HEF1-EFS-p130Cas-like protein) (HEPL) | Docking protein that plays a role in tyrosine kinase-based signaling related to cell adhesion and cell spreading. Regulates PTK2/FAK1 activity, focal adhesion integrity, and cell spreading. {ECO:0000269|PubMed:18256281}. |
| Q9NQL2 | RRAGD | T97 | ochoa | Ras-related GTP-binding protein D (Rag D) (RagD) (EC 3.6.5.-) | Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:34607910). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34607910}. |
| Q9NQW6 | ANLN | T416 | ochoa | Anillin | Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}. |
| Q9NWZ5 | UCKL1 | T53 | ochoa | Uridine-cytidine kinase-like 1 (EC 2.7.1.48) | May contribute to UTP accumulation needed for blast transformation and proliferation. {ECO:0000269|PubMed:12199906}. |
| Q9NYL9 | TMOD3 | T124 | ochoa | Tropomodulin-3 (Ubiquitous tropomodulin) (U-Tmod) | Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity). {ECO:0000250}. |
| Q9NYZ1 | TVP23B | T187 | ochoa | Golgi apparatus membrane protein TVP23 homolog B | None |
| Q9NZM1 | MYOF | T1103 | ochoa | Myoferlin (Fer-1-like protein 3) | Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress. Involved in endocytic recycling. Implicated in VEGF signal transduction by regulating the levels of the receptor KDR (By similarity). {ECO:0000250}. |
| Q9NZN5 | ARHGEF12 | T1186 | ochoa | Rho guanine nucleotide exchange factor 12 (Leukemia-associated RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}. |
| Q9NZQ7 | CD274 | T180 | psp | Programmed cell death 1 ligand 1 (PD-L1) (PDCD1 ligand 1) (Programmed death ligand 1) (hPD-L1) (B7 homolog 1) (B7-H1) (CD antigen CD274) | Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:36727298). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). Can also act as a transcription coactivator: in response to hypoxia, translocates into the nucleus via its interaction with phosphorylated STAT3 and promotes transcription of GSDMC, leading to pyroptosis (PubMed:32929201). {ECO:0000269|PubMed:10581077, ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417, ECO:0000269|PubMed:31399419, ECO:0000269|PubMed:32929201, ECO:0000269|PubMed:36727298}.; FUNCTION: The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28813410, PubMed:28813417). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity). {ECO:0000250|UniProtKB:Q9EP73, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}. |
| Q9P270 | SLAIN2 | T397 | ochoa | SLAIN motif-containing protein 2 | Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Promotes cytoplasmic microtubule nucleation and elongation. Required for normal structure of the microtubule cytoskeleton during interphase. {ECO:0000269|PubMed:21646404}. |
| Q9P275 | USP36 | T675 | ochoa | Ubiquitin carboxyl-terminal hydrolase 36 (EC 2.3.2.-) (EC 3.4.19.12) (Deubiquitinating enzyme 36) (Ubiquitin thioesterase 36) (Ubiquitin-specific-processing protease 36) | Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:19208757, PubMed:22902402, PubMed:29273634). Required for cell and organism viability (PubMed:19208757, PubMed:22902402, PubMed:29273634). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:19208757, PubMed:22902402, PubMed:29273634, PubMed:36912080). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368). Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing (PubMed:36912080). Binds to pre-rRNAs (PubMed:36912080). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341, ECO:0000269|PubMed:35989368, ECO:0000269|PubMed:36912080}. |
| Q9P2D0 | IBTK | T1027 | ochoa | Inhibitor of Bruton tyrosine kinase (IBtk) | Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription. {ECO:0000269|PubMed:11577348}. |
| Q9UBC2 | EPS15L1 | T612 | ochoa | Epidermal growth factor receptor substrate 15-like 1 (Eps15-related protein) (Eps15R) | Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:9407958}. |
| Q9UBD5 | ORC3 | T205 | ochoa | Origin recognition complex subunit 3 (Origin recognition complex subunit Latheo) | Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3. {ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:31160578}. |
| Q9UBU9 | NXF1 | T576 | ochoa | Nuclear RNA export factor 1 (Tip-associated protein) (Tip-associating protein) (mRNA export factor TAP) | Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway) (PubMed:10924507). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex (PubMed:18364396, PubMed:19165146, PubMed:9660949). ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export (PubMed:18364396, PubMed:19165146, PubMed:9660949). Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). {ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:19165146, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:9660949}. |
| Q9UER7 | DAXX | T169 | ochoa | Death domain-associated protein 6 (Daxx) (hDaxx) (ETS1-associated protein 1) (EAP1) (Fas death domain-associated protein) | Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as a histone chaperone that facilitates deposition of histone H3.3. Acts as a targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upon neuronal activation associates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV). Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (PubMed:15016915). {ECO:0000269|PubMed:12140263, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:17942542, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:24530302}. |
| Q9UHQ9 | CYB5R1 | T56 | ochoa | NADH-cytochrome b5 reductase 1 (b5R.1) (EC 1.6.2.2) (Humb5R2) (NAD(P)H:quinone oxidoreductase type 3 polypeptide A2) | NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction. {ECO:0000250}. |
| Q9UHR4 | BAIAP2L1 | T405 | ochoa | BAR/IMD domain-containing adapter protein 2-like 1 (Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1) (BAI1-associated protein 2-like protein 1) (Insulin receptor tyrosine kinase substrate) | May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. {ECO:0000269|PubMed:17430976, ECO:0000269|PubMed:19366662, ECO:0000269|PubMed:22921828}. |
| Q9UJU6 | DBNL | T295 | ochoa | Drebrin-like protein (Cervical SH3P7) (Cervical mucin-associated protein) (Drebrin-F) (HPK1-interacting protein of 55 kDa) (HIP-55) (SH3 domain-containing protein 7) | Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis. Plays a role in the reorganization of the actin cytoskeleton, formation of cell projections, such as neurites, in neuron morphogenesis and synapse formation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for the formation of organized podosome rosettes (By similarity). May act as a common effector of antigen receptor-signaling pathways in leukocytes. Acts as a key component of the immunological synapse that regulates T-cell activation by bridging TCRs and the actin cytoskeleton to gene activation and endocytic processes. {ECO:0000250, ECO:0000269|PubMed:14729663}. |
| Q9UJY4 | GGA2 | T287 | ochoa | ADP-ribosylation factor-binding protein GGA2 (Gamma-adaptin-related protein 2) (Golgi-localized, gamma ear-containing, ARF-binding protein 2) (VHS domain and ear domain of gamma-adaptin) (Vear) | Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif (PubMed:10747088). Mediates export of the GPCR receptor ADRA2B to the cell surface (PubMed:27901063). Regulates retrograde transport of phosphorylated form of BACE1 from endosomes to the trans-Golgi network (PubMed:15615712). {ECO:0000269|PubMed:10747088, ECO:0000269|PubMed:15615712, ECO:0000269|PubMed:27901063}. |
| Q9UKV3 | ACIN1 | T470 | ochoa | Apoptotic chromatin condensation inducer in the nucleus (Acinus) | Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells. {ECO:0000269|PubMed:10490026, ECO:0000269|PubMed:12665594, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22388736}. |
| Q9UKV3 | ACIN1 | T978 | ochoa | Apoptotic chromatin condensation inducer in the nucleus (Acinus) | Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells. {ECO:0000269|PubMed:10490026, ECO:0000269|PubMed:12665594, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22388736}. |
| Q9UKX2 | MYH2 | T792 | ochoa | Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}. |
| Q9UKX2 | MYH2 | T1727 | ochoa | Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}. |
| Q9UKX7 | NUP50 | T235 | ochoa | Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) | Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}. |
| Q9UKX7 | NUP50 | T307 | ochoa | Nuclear pore complex protein Nup50 (50 kDa nucleoporin) (Nuclear pore-associated protein 60 kDa-like) (Nucleoporin Nup50) | Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:20016008). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:20016008). Interacts with regulatory proteins of cell cycle progression including CDKN1B (By similarity). This interaction is required for correct intracellular transport and degradation of CDKN1B (By similarity). {ECO:0000250|UniProtKB:Q9JIH2, ECO:0000269|PubMed:20016008}. |
| Q9UL16 | CFAP45 | T62 | ochoa | Cilia- and flagella-associated protein 45 (Coiled-coil domain-containing protein 19) (Nasopharyngeal epithelium-specific protein 1) | Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (PubMed:36191189). It is an AMP-binding protein that may facilitate dynein ATPase-dependent ciliary and flagellar beating via adenine nucleotide homeostasis. May function as a donor of AMP to AK8 and hence promote ADP production (PubMed:33139725). {ECO:0000250|UniProtKB:Q32LN4, ECO:0000269|PubMed:33139725, ECO:0000269|PubMed:36191189}. |
| Q9UL16 | CFAP45 | T68 | ochoa | Cilia- and flagella-associated protein 45 (Coiled-coil domain-containing protein 19) (Nasopharyngeal epithelium-specific protein 1) | Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (PubMed:36191189). It is an AMP-binding protein that may facilitate dynein ATPase-dependent ciliary and flagellar beating via adenine nucleotide homeostasis. May function as a donor of AMP to AK8 and hence promote ADP production (PubMed:33139725). {ECO:0000250|UniProtKB:Q32LN4, ECO:0000269|PubMed:33139725, ECO:0000269|PubMed:36191189}. |
| Q9ULH1 | ASAP1 | T1004 | ochoa | Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 (130 kDa phosphatidylinositol 4,5-bisphosphate-dependent ARF1 GTPase-activating protein) (ADP-ribosylation factor-directed GTPase-activating protein 1) (ARF GTPase-activating protein 1) (Development and differentiation-enhancing factor 1) (DEF-1) (Differentiation-enhancing factor 1) (PIP2-dependent ARF1 GAP) | Possesses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6. May coordinate membrane trafficking with cell growth or actin cytoskeleton remodeling by binding to both SRC and PIP2. May function as a signal transduction protein involved in the differentiation of fibroblasts into adipocytes and possibly other cell types. Part of the ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which direct preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:25673879). {ECO:0000250, ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:25673879}. |
| Q9ULI0 | ATAD2B | T1377 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9ULV5 | HSF4 | T471 | psp | Heat shock factor protein 4 (HSF 4) (hHSF4) (Heat shock transcription factor 4) (HSTF 4) | Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146). Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity). In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity). May be involved in DNA repair through the transcriptional regulation of RAD51 (PubMed:22587838). May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (PubMed:28981088). In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (By similarity). {ECO:0000250|UniProtKB:Q5CZP2, ECO:0000250|UniProtKB:Q9R0L1, ECO:0000269|PubMed:22587838, ECO:0000269|PubMed:23507146, ECO:0000269|PubMed:28981088}.; FUNCTION: [Isoform HSF4A]: Transcriptional repressor. {ECO:0000269|PubMed:10488131}.; FUNCTION: [Isoform HSF4B]: Transcriptional activator. {ECO:0000269|PubMed:10488131, ECO:0000269|PubMed:16371476}. |
| Q9ULW0 | TPX2 | T59 | ochoa | Targeting protein for Xklp2 (Differentially expressed in cancerous and non-cancerous lung cells 2) (DIL-2) (Hepatocellular carcinoma-associated antigen 519) (Hepatocellular carcinoma-associated antigen 90) (Protein fls353) (Restricted expression proliferation-associated protein 100) (p100) | Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules (PubMed:18663142, PubMed:19208764, PubMed:37728657). Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation (PubMed:18663142, PubMed:19208764). TPX2 is inactivated upon binding to importin-alpha (PubMed:26165940). At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation (PubMed:26165940). {ECO:0000269|PubMed:18663142, ECO:0000269|PubMed:19208764, ECO:0000269|PubMed:26165940}. |
| Q9UPN3 | MACF1 | T1998 | ochoa | Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 (620 kDa actin-binding protein) (ABP620) (Actin cross-linking family protein 7) (Macrophin-1) (Trabeculin-alpha) | [Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27693509}. |
| Q9UPW0 | FOXJ3 | T65 | ochoa | Forkhead box protein J3 | Transcriptional activator of MEF2C involved in the regulation of adult muscle fiber type identity and skeletal muscle regeneration (By similarity). Plays an important role in spermatogenesis (By similarity). Required for the survival of spermatogonia and participates in spermatocyte meiosis (By similarity). {ECO:0000250|UniProtKB:Q8BUR3}. |
| Q9Y289 | SLC5A6 | T78 | psp | Sodium-dependent multivitamin transporter (Na(+)-dependent multivitamin transporter) (hSMVT) (Solute carrier family 5 member 6) | Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide (PubMed:10329687, PubMed:15561972, PubMed:19211916, PubMed:20980265, PubMed:21570947, PubMed:22015582, PubMed:25809983, PubMed:25971966, PubMed:27904971, PubMed:28052864, PubMed:31754459). Functions as a Na(+)-coupled substrate symporter where the stoichiometry of Na(+):substrate is 2:1, creating an electrochemical Na(+) gradient used as driving force for substrate uptake (PubMed:10329687, PubMed:20980265). Required for biotin and pantothenate uptake in the intestine across the brush border membrane (PubMed:19211916). Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (By similarity). Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (PubMed:25809983). {ECO:0000250|UniProtKB:Q5U4D8, ECO:0000269|PubMed:10329687, ECO:0000269|PubMed:15561972, ECO:0000269|PubMed:19211916, ECO:0000269|PubMed:20980265, ECO:0000269|PubMed:21570947, ECO:0000269|PubMed:22015582, ECO:0000269|PubMed:25809983, ECO:0000269|PubMed:25971966, ECO:0000269|PubMed:27904971, ECO:0000269|PubMed:28052864, ECO:0000269|PubMed:31754459}. |
| Q9Y2K5 | R3HDM2 | T856 | ochoa | R3H domain-containing protein 2 | None |
| Q9Y2X9 | ZNF281 | T399 | ochoa | Zinc finger protein 281 (GC-box-binding zinc finger protein 1) (Transcription factor ZBP-99) (Zinc finger DNA-binding protein 99) | Transcription repressor that plays a role in regulation of embryonic stem cells (ESCs) differentiation. Required for ESCs differentiation and acts by mediating autorepression of NANOG in ESCs: binds to the NANOG promoter and promotes association of NANOG protein to its own promoter and recruits the NuRD complex, which deacetylates histones. Not required for establishement and maintenance of ESCs (By similarity). Represses the transcription of a number of genes including GAST, ODC1 and VIM. Binds to the G-rich box in the enhancer region of these genes. {ECO:0000250, ECO:0000269|PubMed:10448078, ECO:0000269|PubMed:12771217}. |
| Q9Y3C5 | RNF11 | T63 | ochoa | RING finger protein 11 | Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of TNFAIP3 to RIPK1 after TNF stimulation. TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Recruits STAMBP to the E3 ubiquitin-ligase SMURF2 for ubiquitination, leading to its degradation by the 26S proteasome. {ECO:0000269|PubMed:14755250}. |
| Q9Y3C5 | RNF11 | T135 | psp | RING finger protein 11 | Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of TNFAIP3 to RIPK1 after TNF stimulation. TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Recruits STAMBP to the E3 ubiquitin-ligase SMURF2 for ubiquitination, leading to its degradation by the 26S proteasome. {ECO:0000269|PubMed:14755250}. |
| Q9Y3L5 | RAP2C | T61 | ochoa | Ras-related protein Rap-2c (EC 3.6.5.2) | Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. May play a role in cytoskeletal rearrangements and regulate cell spreading through activation of the effector TNIK. May play a role in SRE-mediated gene transcription. {ECO:0000269|PubMed:17447155}. |
| Q9Y3R5 | DOP1B | T409 | ochoa | Protein DOP1B | May play a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and MON2, regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation. {ECO:0000269|PubMed:30213940}. |
| Q9Y490 | TLN1 | T1254 | 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}. |
| Q9Y4F9 | RIPOR2 | T572 | ochoa | Rho family-interacting cell polarization regulator 2 | Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization (PubMed:17150207, PubMed:23241886, PubMed:24687993, PubMed:24958875, PubMed:25588844, PubMed:27556504). Inhibits chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration (PubMed:23241886). Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion (By similarity). Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear (By similarity). Plays a role for maintaining the structural organization of the basal domain of stereocilia (By similarity). Involved in mechanosensory hair cell function (By similarity). Required for normal hearing (PubMed:24958875). {ECO:0000250|UniProtKB:Q80U16, ECO:0000269|PubMed:17150207, ECO:0000269|PubMed:23241886, ECO:0000269|PubMed:24687993, ECO:0000269|PubMed:24958875, ECO:0000269|PubMed:27556504}.; FUNCTION: [Isoform 2]: Acts as an inhibitor of the small GTPase RHOA (PubMed:25588844). Plays a role in fetal mononuclear myoblast differentiation by promoting filopodia and myotube formation (PubMed:17150207). Maintains naive T lymphocytes in a quiescent state (PubMed:27556504). {ECO:0000269|PubMed:17150207, ECO:0000269|PubMed:25588844, ECO:0000269|PubMed:27556504}. |
| Q9Y4G8 | RAPGEF2 | T602 | ochoa | Rap guanine nucleotide exchange factor 2 (Cyclic nucleotide ras GEF) (CNrasGEF) (Neural RAP guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) (RA-GEF-1) (Ras/Rap1-associating GEF-1) | Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Also acts as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10548487, PubMed:10608844, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Also provides inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:10608883, ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:10934204, ECO:0000269|PubMed:11359771, ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:23800469}. |
| Q9Y4H4 | GPSM3 | T62 | ochoa | G-protein-signaling modulator 3 (Activator of G-protein signaling 4) (G18.1b) (Protein G18) | Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins. {ECO:0000269|PubMed:14656218, ECO:0000269|PubMed:15096500}. |
| Q9Y608 | LRRFIP2 | T339 | ochoa | Leucine-rich repeat flightless-interacting protein 2 (LRR FLII-interacting protein 2) | May function as activator of the canonical Wnt signaling pathway, in association with DVL3, upstream of CTNNB1/beta-catenin. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:15677333, ECO:0000269|PubMed:19265123}. |
| Q9Y623 | MYH4 | T1725 | ochoa | Myosin-4 (Myosin heavy chain 2b) (MyHC-2b) (Myosin heavy chain 4) (Myosin heavy chain IIb) (MyHC-IIb) (Myosin heavy chain, skeletal muscle, fetal) | Muscle contraction. |
| Q9Y6Q5 | AP1M2 | T70 | ochoa | AP-1 complex subunit mu-2 (AP-mu chain family member mu1B) (Adaptor protein complex AP-1 subunit mu-2) (Adaptor-related protein complex 1 subunit mu-2) (Clathrin assembly protein complex 1 mu-2 medium chain 2) (Golgi adaptor HA1/AP1 adaptin mu-2 subunit) (Mu-adaptin 2) (Mu1B-adaptin) | Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. |
| Q9Y6Q9 | NCOA3 | T1059 | psp | Nuclear receptor coactivator 3 (NCoA-3) (EC 2.3.1.48) (ACTR) (Amplified in breast cancer 1 protein) (AIB-1) (CBP-interacting protein) (pCIP) (Class E basic helix-loop-helix protein 42) (bHLHe42) (Receptor-associated coactivator 3) (RAC-3) (Steroid receptor coactivator protein 3) (SRC-3) (Thyroid hormone receptor activator molecule 1) (TRAM-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit. |
| V9GY48 | None | T177 | ochoa | Zinc finger CCCH-type with G patch domain-containing protein | None |
| O95071 | UBR5 | T119 | Sugiyama | 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}. |
| O95373 | IPO7 | T997 | Sugiyama | Importin-7 (Imp7) (Ran-binding protein 7) (RanBP7) | Functions in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, is thought to serve itself as receptor for nuclear localization signals (NLS) and to promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607). In association with KPNB1 mediates the nuclear import of H1 histone and the Ran-binding site of IPO7 is not required but synergizes with that of KPNB1 in importin/substrate complex dissociation. Promotes odontoblast differentiation via promoting nuclear translocation of DLX3, KLF4, SMAD2, thereby facilitating the transcription of target genes that play a role in odontoblast differentiation (By similarity). Facilitates BMP4-induced translocation of SMAD1 to the nucleus and recruitment to the MSX1 gene promoter, thereby promotes the expression of the odontogenic regulator MSX1 in dental mesenchymal cells (By similarity). Also promotes odontoblast differentiation by facilitating the nuclear translocation of HDAC6 and subsequent repression of RUNX2 expression (By similarity). Inhibits osteoblast differentiation by inhibiting nuclear translocation of RUNX2 and therefore inhibition of RUNX2 target gene transcription (By similarity). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. {ECO:0000250|UniProtKB:Q9EPL8, ECO:0000269|PubMed:10228156, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9687515}.; FUNCTION: (Microbial infection) Mediates the nuclear import of HIV-1 reverse transcription complex (RTC) integrase. Binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000269|PubMed:12853482, ECO:0000269|PubMed:16704975}. |
| P09211 | GSTP1 | T68 | Sugiyama | Glutathione S-transferase P (EC 2.5.1.18) (GST class-pi) (GSTP1-1) | Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration. {ECO:0000269|PubMed:21046276, ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9084911}. |
| P13639 | EEF2 | T484 | Sugiyama | Elongation factor 2 (EF-2) (EC 3.6.5.-) | Catalyzes the GTP-dependent ribosomal translocation step during translation elongation (PubMed:26593721). During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively (PubMed:26593721). Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome (PubMed:26593721). {ECO:0000269|PubMed:26593721}. |
| P56192 | MARS1 | T710 | Sugiyama | Methionine--tRNA ligase, cytoplasmic (EC 6.1.1.10) (Methionyl-tRNA synthetase) (MetRS) | Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:11714285). Plays a role in the synthesis of ribosomal RNA in the nucleolus (PubMed:10791971). {ECO:0000269|PubMed:10791971, ECO:0000269|PubMed:11714285, ECO:0000269|PubMed:33909043}. |
| Q9Y3F4 | STRAP | T48 | Sugiyama | Serine-threonine kinase receptor-associated protein (MAP activator with WD repeats) (UNR-interacting protein) (WD-40 repeat protein PT-WD) | The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein. {ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:18984161}. |
| P11047 | LAMC1 | T258 | EPSD|PSP | Laminin subunit gamma-1 (Laminin B2 chain) (Laminin-1 subunit gamma) (Laminin-10 subunit gamma) (Laminin-11 subunit gamma) (Laminin-2 subunit gamma) (Laminin-3 subunit gamma) (Laminin-4 subunit gamma) (Laminin-6 subunit gamma) (Laminin-7 subunit gamma) (Laminin-8 subunit gamma) (Laminin-9 subunit gamma) (S-laminin subunit gamma) (S-LAM gamma) | Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. |
| P33992 | MCM5 | T633 | EPSD|PSP | DNA replication licensing factor MCM5 (EC 3.6.4.12) (CDC46 homolog) (P1-CDC46) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232}. |
| P36507 | MAP2K2 | T59 | EPSD|PSP | Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2) | Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}. |
| P39748 | FEN1 | T195 | EPSD|PSP | Flap endonuclease 1 (FEN-1) (EC 3.1.-.-) (DNase IV) (Flap structure-specific endonuclease 1) (Maturation factor 1) (MF1) (hFEN-1) | Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}. |
| P49327 | FASN | T2215 | Sugiyama | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P62899 | RPL31 | T107 | Sugiyama | Large ribosomal subunit protein eL31 (60S ribosomal protein L31) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q02750 | MAP2K1 | T55 | EPSD|PSP | Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}. |
| Q8N4C8 | MINK1 | T280 | EPSD|PSP | Misshapen-like kinase 1 (EC 2.7.11.1) (GCK family kinase MiNK) (MAPK/ERK kinase kinase kinase 6) (MEK kinase kinase 6) (MEKKK 6) (Misshapen/NIK-related kinase) (Mitogen-activated protein kinase kinase kinase kinase 6) | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking (PubMed:10708748, PubMed:16337592). Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons (By similarity). Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1 (PubMed:18930710, PubMed:21690388). Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1 (By similarity). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000250|UniProtKB:F1LP90, ECO:0000250|UniProtKB:Q9JM52, ECO:0000269|PubMed:10708748, ECO:0000269|PubMed:16337592, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. |
| P46776 | RPL27A | T80 | Sugiyama | Large ribosomal subunit protein uL15 (60S ribosomal protein L27a) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| P55084 | HADHB | T356 | Sugiyama | Trifunctional enzyme subunit beta, mitochondrial (TP-beta) [Includes: 3-ketoacyl-CoA thiolase (EC 2.3.1.155) (EC 2.3.1.16) (Acetyl-CoA acyltransferase) (Beta-ketothiolase)] | Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:29915090, PubMed:30850536, PubMed:8135828). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity (PubMed:29915090, PubMed:30850536, PubMed:8135828). {ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}. |
| P61221 | ABCE1 | T157 | Sugiyama | ATP-binding cassette sub-family E member 1 (EC 3.6.5.-) (2'-5'-oligoadenylate-binding protein) (HuHP68) (RNase L inhibitor) (Ribonuclease 4 inhibitor) (RNS4I) | Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly (PubMed:20122402, PubMed:21448132). Able to hydrolyze ATP, GTP, UTP and CTP (PubMed:20122402). Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits (PubMed:20122402, PubMed:21448132). Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota) (PubMed:20122402, PubMed:21448132). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132). Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA (PubMed:29861391). As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy (PubMed:29861391). RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) to RNASEL (PubMed:9660177). Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway (PubMed:11585831, PubMed:9660177, PubMed:9847332). {ECO:0000269|PubMed:11585831, ECO:0000269|PubMed:20122402, ECO:0000269|PubMed:21448132, ECO:0000269|PubMed:29861391, ECO:0000269|PubMed:9660177, ECO:0000269|PubMed:9847332}.; FUNCTION: (Microbial infection) May act as a chaperone for post-translational events during HIV-1 capsid assembly. {ECO:0000269|PubMed:9847332}.; FUNCTION: (Microbial infection) Plays a role in the down-regulation of the 2-5A/RNASEL pathway during encephalomyocarditis virus (EMCV) and HIV-1 infections. {ECO:0000269|PubMed:9660177}. |
| O43283 | MAP3K13 | T32 | Sugiyama | Mitogen-activated protein kinase kinase kinase 13 (EC 2.7.11.25) (Leucine zipper-bearing kinase) (Mixed lineage kinase) (MLK) | Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B. {ECO:0000269|PubMed:11726277, ECO:0000269|PubMed:12492477, ECO:0000269|PubMed:9353328}. |
| Q9BS26 | ERP44 | T155 | Sugiyama | Endoplasmic reticulum resident protein 44 (ER protein 44) (ERp44) (Thioredoxin domain-containing protein 4) | Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the calcium channel activity of ITPR1 (PubMed:15652484). May have a role in the control of oxidative protein folding in the endoplasmic reticulum (PubMed:11847130, PubMed:14517240, PubMed:29858230). Required to retain ERO1A and ERO1B in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230). {ECO:0000269|PubMed:11847130, ECO:0000269|PubMed:14517240, ECO:0000269|PubMed:15652484, ECO:0000269|PubMed:29858230}. |
| O60245 | PCDH7 | T251 | Sugiyama | Protocadherin-7 (Brain-heart protocadherin) (BH-Pcdh) | None |
| P49588 | AARS1 | T164 | Sugiyama | Alanine--tRNA ligase, cytoplasmic (EC 6.1.1.7) (Alanyl-tRNA synthetase) (AlaRS) (Protein lactyltransferase AARS1) (EC 6.-.-.-) (Renal carcinoma antigen NY-REN-42) | Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:33909043). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:27622773, PubMed:27911835, PubMed:28493438, PubMed:29273753). In presence of high levels of lactate, also acts as a protein lactyltransferase that mediates lactylation of lysine residues in target proteins, such as TEAD1, TP53/p53 and YAP1 (PubMed:38512451, PubMed:38653238). Protein lactylation takes place in a two-step reaction: lactate is first activated by ATP to form lactate-AMP and then transferred to lysine residues of target proteins (PubMed:38512451, PubMed:38653238, PubMed:39322678). Acts as an inhibitor of TP53/p53 activity by catalyzing lactylation of TP53/p53 (PubMed:38653238). Acts as a positive regulator of the Hippo pathway by mediating lactylation of TEAD1 and YAP1 (PubMed:38512451). {ECO:0000269|PubMed:27622773, ECO:0000269|PubMed:27911835, ECO:0000269|PubMed:28493438, ECO:0000269|PubMed:29273753, ECO:0000269|PubMed:33909043, ECO:0000269|PubMed:38512451, ECO:0000269|PubMed:38653238, ECO:0000269|PubMed:39322678}. |
| P39687 | ANP32A | T143 | Sugiyama | Acidic leucine-rich nuclear phosphoprotein 32 family member A (Acidic nuclear phosphoprotein pp32) (pp32) (Leucine-rich acidic nuclear protein) (LANP) (Mapmodulin) (Potent heat-stable protein phosphatase 2A inhibitor I1PP2A) (Putative HLA-DR-associated protein I) (PHAPI) | Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription (PubMed:10400610, PubMed:11360199, PubMed:16341127, PubMed:18439902). Promotes apoptosis by favouring the activation of caspase-9/CASP9 and allowing apoptosome formation (PubMed:18439902). In addition, plays a role in the modulation of histone acetylation and transcription as part of the INHAT (inhibitor of histone acetyltransferases) complex. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking (PubMed:11830591). Preferentially binds to unmodified histone H3 and sterically inhibiting its acetylation and phosphorylation leading to cell growth inhibition (PubMed:16341127). Participates in other biochemical processes such as regulation of mRNA nuclear-to-cytoplasmic translocation and stability by its association with ELAVL1 (Hu-antigen R) (PubMed:18180367). Plays a role in E4F1-mediated transcriptional repression as well as inhibition of protein phosphatase 2A (PubMed:15642345, PubMed:17557114). {ECO:0000269|PubMed:10400610, ECO:0000269|PubMed:11360199, ECO:0000269|PubMed:11830591, ECO:0000269|PubMed:15642345, ECO:0000269|PubMed:16341127, ECO:0000269|PubMed:17557114, ECO:0000269|PubMed:18180367, ECO:0000269|PubMed:18439902}.; FUNCTION: (Microbial infection) Plays an essential role in influenza A, B and C viral genome replication (PubMed:30666459, PubMed:32694517, PubMed:33045004, PubMed:33208942). Mechanistically, mediates the assembly of the viral replicase asymmetric dimers composed of PB1, PB2 and PA via its N-terminal region (PubMed:33208942). Also plays an essential role in foamy virus mRNA export from the nucleus (PubMed:21159877). {ECO:0000269|PubMed:21159877, ECO:0000269|PubMed:30666459, ECO:0000269|PubMed:32694517, ECO:0000269|PubMed:33045004, ECO:0000269|PubMed:33208942}. |
| O75116 | ROCK2 | T235 | Sugiyama | Rho-associated protein kinase 2 (EC 2.7.11.1) (Rho kinase 2) (Rho-associated, coiled-coil-containing protein kinase 2) (Rho-associated, coiled-coil-containing protein kinase II) (ROCK-II) (p164 ROCK-2) | Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10579722, ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}. |
| Q13464 | ROCK1 | T219 | Sugiyama | Rho-associated protein kinase 1 (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-35) (Rho-associated, coiled-coil-containing protein kinase 1) (Rho-associated, coiled-coil-containing protein kinase I) (ROCK-I) (p160 ROCK-1) (p160ROCK) | Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:23093407, PubMed:23355470, PubMed:8617235, PubMed:9722579). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (PubMed:19036714). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation (PubMed:19181962). Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (PubMed:19997641). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity). {ECO:0000250|UniProtKB:P70335, ECO:0000250|UniProtKB:Q8MIT6, ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11283607, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18573880, ECO:0000269|PubMed:18694941, ECO:0000269|PubMed:19036714, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19181962, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21072057, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:8617235, ECO:0000269|PubMed:9722579}. |
| P13674 | P4HA1 | T140 | Sugiyama | Prolyl 4-hydroxylase subunit alpha-1 (4-PH alpha-1) (EC 1.14.11.2) (Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1) | Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. {ECO:0000269|PubMed:9211872}. |
| Q8N1G4 | LRRC47 | T371 | Sugiyama | Leucine-rich repeat-containing protein 47 | None |
| P54577 | YARS1 | T130 | Sugiyama | Tyrosine--tRNA ligase, cytoplasmic (EC 6.1.1.1) (Tyrosyl-tRNA synthetase) (TyrRS) [Cleaved into: Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed] | Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949). Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949). {ECO:0000269|PubMed:25533949, ECO:0000305|PubMed:16429158, ECO:0000305|PubMed:9162081}. |
| P00519 | ABL1 | T389 | Sugiyama | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P42684 | ABL2 | T435 | Sugiyama | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P62851 | RPS25 | T54 | Sugiyama | Small ribosomal subunit protein eS25 (40S ribosomal protein S25) | 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). {ECO:0000269|PubMed:23636399}. |
| P07947 | YES1 | T241 | Sugiyama | Tyrosine-protein kinase Yes (EC 2.7.10.2) (Proto-oncogene c-Yes) (p61-Yes) | Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity (PubMed:26979622). {ECO:0000269|PubMed:11901164, ECO:0000269|PubMed:18479465, ECO:0000269|PubMed:19276087, ECO:0000269|PubMed:21566460, ECO:0000269|PubMed:21713032, ECO:0000269|PubMed:26979622}. |
| Q6NVY1 | HIBCH | T249 | Sugiyama | 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial (EC 3.1.2.4) (3-hydroxyisobutyryl-coenzyme A hydrolase) (HIB-CoA hydrolase) (HIBYL-CoA-H) | Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA. {ECO:0000269|PubMed:8824301}. |
| Q14258 | TRIM25 | T246 | Sugiyama | E3 ubiquitin/ISG15 ligase TRIM25 (EC 6.3.2.n3) (Estrogen-responsive finger protein) (RING finger protein 147) (RING-type E3 ubiquitin transferase) (EC 2.3.2.27) (RING-type E3 ubiquitin transferase TRIM25) (Tripartite motif-containing protein 25) (Ubiquitin/ISG15-conjugating enzyme TRIM25) (Zinc finger protein 147) | Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase (PubMed:16352599). Involved in innate immune defense against viruses by mediating ubiquitination of RIGI and IFIH1 (PubMed:17392790, PubMed:29357390, PubMed:30193849, PubMed:31710640, PubMed:33849980, PubMed:36045682). Mediates 'Lys-63'-linked polyubiquitination of the RIGI N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection (PubMed:17392790, PubMed:23950712). Mediates 'Lys-63'-linked polyubiquitination of IFIH1 (PubMed:30193849). Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway (PubMed:16352599, PubMed:17069755). Mediates estrogen action in various target organs (PubMed:22452784). Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (By similarity). Plays an essential role in the antiviral activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the replication of certain viruses. Mechanistically, mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1 that is required for its optimal binding to target mRNA (PubMed:28060952, PubMed:28202764). Also mediates the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (PubMed:36067236). {ECO:0000250|UniProtKB:Q61510, ECO:0000269|PubMed:16352599, ECO:0000269|PubMed:17069755, ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:22452784, ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:29357390, ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:31710640, ECO:0000269|PubMed:33849980, ECO:0000269|PubMed:36045682, ECO:0000269|PubMed:36067236}. |
| P23381 | WARS1 | T207 | Sugiyama | Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS] | Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp). {ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220}.; FUNCTION: [Isoform 1]: Has no angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}.; FUNCTION: [T2-TrpRS]: Possesses an angiostatic activity but has no aminoacylation activity (PubMed:11773625, PubMed:11773626, PubMed:14630953). Inhibits fluid shear stress-activated responses of endothelial cells (PubMed:14630953). Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression (PubMed:14630953). {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:14630953}.; FUNCTION: [Isoform 2]: Has an angiostatic activity. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626}. |
| P17980 | PSMC3 | T166 | Sugiyama | 26S proteasome regulatory subunit 6A (26S proteasome AAA-ATPase subunit RPT5) (Proteasome 26S subunit ATPase 3) (Proteasome subunit P50) (Tat-binding protein 1) (TBP-1) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC3 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798}. |
| P50395 | GDI2 | T194 | Sugiyama | Rab GDP dissociation inhibitor beta (Rab GDI beta) (Guanosine diphosphate dissociation inhibitor 2) (GDI-2) | GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking (PubMed:25860027). Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A (PubMed:25860027). {ECO:0000269|PubMed:25860027}. |
| P05023 | ATP1A1 | T686 | Sugiyama | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P20020 | ATP2B1 | T1116 | iPTMNet|EPSD | Plasma membrane calcium-transporting ATPase 1 (EC 7.2.2.10) (Plasma membrane calcium ATPase isoform 1) (PMCA1) (Plasma membrane calcium pump isoform 1) | Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis (PubMed:35358416). Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction. Positively regulates bone mineralization through absorption of calcium from the intestine. Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts (By similarity). Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells (PubMed:29104511). May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles. {ECO:0000250|UniProtKB:G5E829, ECO:0000269|PubMed:29104511, ECO:0000269|PubMed:35358416}. |
| P53041 | PPP5C | T121 | Sugiyama | Serine/threonine-protein phosphatase 5 (PP5) (EC 3.1.3.16) (Protein phosphatase T) (PP-T) (PPT) | Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT (PubMed:14734805, PubMed:14764652, PubMed:14871926, PubMed:15383005, PubMed:15546861, PubMed:16260606, PubMed:16790549, PubMed:16892053, PubMed:19176521, PubMed:19948726, PubMed:21144835, PubMed:22399290, PubMed:22781750, PubMed:23102700, PubMed:30699359, PubMed:9000529). Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses (PubMed:14734805, PubMed:14764652, PubMed:14871926, PubMed:15383005, PubMed:15546861, PubMed:16260606, PubMed:16790549, PubMed:16892053, PubMed:19176521, PubMed:19948726, PubMed:21144835, PubMed:22399290, PubMed:22781750, PubMed:23102700, PubMed:30699359, PubMed:9000529). Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1 (PubMed:14871926, PubMed:16260606, PubMed:21144835). Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress (PubMed:23102700). Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function (By similarity). Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1 (By similarity). Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E (PubMed:16790549). May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels (PubMed:22781750). Dephosphorylates and may play a role in the regulation of TAU/MAPT (PubMed:15546861). Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2 (By similarity). Dephosphorylate FNIP1, disrupting interaction with HSP90AA1/Hsp90 (PubMed:30699359). {ECO:0000250|UniProtKB:P53042, ECO:0000250|UniProtKB:Q60676, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22399290, ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:9000529}. |
| Q99471 | PFDN5 | T88 | Sugiyama | Prefoldin subunit 5 (Myc modulator 1) (c-Myc-binding protein Mm-1) | Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. Represses the transcriptional activity of MYC. {ECO:0000269|PubMed:9630229}. |
| O75369 | FLNB | T997 | Sugiyama | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| P24046 | GABRR1 | T394 | SIGNOR|iPTMNet|EPSD | Gamma-aminobutyric acid receptor subunit rho-1 (GABA(A) receptor subunit rho-1) (GABAAR subunit rho-1) (GABA(C) receptor) | Rho subunit of the pentameric ligand-gated chloride channels responsible for mediating the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain (PubMed:37659407). Rho-containing GABA-gated chloride channels are a subclass of GABA(A) receptors (GABAARs) entirely composed of rho subunits, where GABA molecules bind at the rho intersubunit interfaces (PubMed:37659407). When activated by GABA, rho-GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:37659407). Rho-1 subunits are primarily expressed in retina where rho-1-containing GABAARs may play a role in retinal neurotransmission (PubMed:1849271). Rho-1 GABAARs are also involved in neuronal tonic (extrasynaptic) and phasic (synaptic) transmission in the Purkinje neurons of the cerebellum (By similarity). Rho-1 GABAARs may also contribute to the regulation of glial development in the cerebellum by controlling extrasynaptic transmission (By similarity). {ECO:0000250|UniProtKB:P56475, ECO:0000269|PubMed:1849271, ECO:0000269|PubMed:37659407}. |
| O00541 | PES1 | T365 | Sugiyama | Pescadillo homolog | Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome. {ECO:0000255|HAMAP-Rule:MF_03028, ECO:0000269|PubMed:16738141, ECO:0000269|PubMed:17189298, ECO:0000269|PubMed:17353269}. |
| P43403 | ZAP70 | T207 | 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}. |
| Q99933 | BAG1 | T202 | Sugiyama | BAG family molecular chaperone regulator 1 (BAG-1) (Bcl-2-associated athanogene 1) | Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70 (PubMed:24318877, PubMed:27474739, PubMed:9873016). Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity (PubMed:12724406). Markedly increases the anti-cell death function of BCL2 induced by various stimuli (PubMed:9305631). Involved in the STUB1-mediated proteasomal degradation of ESR1 in response to age-related circulating estradiol (17-beta-estradiol/E2) decline, thereby promotes neuronal apoptosis in response to ischemic reperfusion injury (By similarity). {ECO:0000250|UniProtKB:B0K019, ECO:0000269|PubMed:12724406, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:9305631, ECO:0000269|PubMed:9873016}. |
| P45985 | MAP2K4 | T66 | Sugiyama | Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}. |
| P13797 | PLS3 | T117 | Sugiyama | Plastin-3 (T-fimbrin) (T-plastin) | Actin-bundling protein. |
| Q96KB5 | PBK | T301 | Sugiyama | Lymphokine-activated killer T-cell-originated protein kinase (EC 2.7.12.2) (Cancer/testis antigen 84) (CT84) (MAPKK-like protein kinase) (Nori-3) (PDZ-binding kinase) (Spermatogenesis-related protein kinase) (SPK) (T-LAK cell-originated protein kinase) | Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage. {ECO:0000269|PubMed:10781613, ECO:0000269|PubMed:17482142}. |
| P46776 | RPL27A | T86 | Sugiyama | Large ribosomal subunit protein uL15 (60S ribosomal protein L27a) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q9NZL9 | MAT2B | T37 | Sugiyama | Methionine adenosyltransferase 2 subunit beta (Methionine adenosyltransferase II beta) (MAT II beta) (Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase) | Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine (PubMed:10644686, PubMed:23189196, PubMed:25075345). Can bind NADP (in vitro) (PubMed:23189196, PubMed:23425511). {ECO:0000269|PubMed:10644686, ECO:0000269|PubMed:23189196, ECO:0000269|PubMed:23425511, ECO:0000269|PubMed:25075345}. |
| P35579 | MYH9 | T1146 | Sugiyama | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P52565 | ARHGDIA | T91 | SIGNOR | Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) | Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}. |
| P32929 | CTH | T355 | SIGNOR | Cystathionine gamma-lyase (CGL) (CSE) (EC 4.4.1.1) (Cysteine desulfhydrase) (Cysteine-protein sulfhydrase) (Gamma-cystathionase) (Homocysteine desulfhydrase) (EC 4.4.1.2) | Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate (PubMed:10212249, PubMed:18476726, PubMed:19261609, PubMed:19961860). Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione (PubMed:18476726). Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce the endogenous gaseous signaling molecule hydrogen sulfide (H2S) (PubMed:10212249, PubMed:19019829, PubMed:19261609, PubMed:19961860). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer's disease) (PubMed:19261609). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (PubMed:19261609). Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function (PubMed:22169477). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (Probable) (PubMed:29254196). Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (By similarity). Can also accept homoserine as substrate (By similarity). Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity). {ECO:0000250|UniProtKB:P18757, ECO:0000250|UniProtKB:Q8VCN5, ECO:0000269|PubMed:10212249, ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19019829, ECO:0000269|PubMed:19261609, ECO:0000269|PubMed:19961860, ECO:0000269|PubMed:22169477, ECO:0000269|PubMed:29254196, ECO:0000303|PubMed:18476726, ECO:0000305|PubMed:18476726, ECO:0000305|PubMed:19019829}. |
| Q9H2X6 | HIPK2 | T1116 | SIGNOR | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| P35568 | IRS1 | T88 | SIGNOR | 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}. |
| O94804 | STK10 | T896 | Sugiyama | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
| Q00534 | CDK6 | T282 | Sugiyama | Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) | Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}. |
| P23396 | RPS3 | T26 | Sugiyama | Small ribosomal subunit protein uS3 (40S ribosomal protein S3) (EC 4.2.99.18) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:8706699). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:8706699). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (PubMed:15707971). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Has also been shown to bind with similar affinity to intact and damaged DNA (PubMed:18610840). Stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571). Enhances the uracil excision activity of UNG1 (PubMed:18973764). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (PubMed:18045535). Represses its own translation by binding to its cognate mRNA (PubMed:20217897). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408). {ECO:0000269|PubMed:14706345, ECO:0000269|PubMed:14988002, ECO:0000269|PubMed:15518571, ECO:0000269|PubMed:15707971, ECO:0000269|PubMed:17049931, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:18610840, ECO:0000269|PubMed:18973764, ECO:0000269|PubMed:19656744, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:22510408, ECO:0000269|PubMed:23131551, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:23911537, ECO:0000269|PubMed:7775413, ECO:0000269|PubMed:8706699}. |
| P33993 | MCM7 | T582 | Sugiyama | DNA replication licensing factor MCM7 (EC 3.6.4.12) (CDC47 homolog) (P1.1-MCM3) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:25661590, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for S-phase checkpoint activation upon UV-induced damage. {ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:25661590, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}. |
| Q96RI1 | NR1H4 | T456 | SIGNOR | Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14) | Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response (PubMed:10334992, PubMed:10334993, PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:12754200, PubMed:15471871, PubMed:17895379). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:10514450, PubMed:15239098, PubMed:16269519). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA (PubMed:12806625, PubMed:16946559). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly (PubMed:12554753, PubMed:12660231, PubMed:15337761). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:11927623, PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:21242261). Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 (PubMed:19864602). Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity). {ECO:0000250|UniProtKB:Q60641, ECO:0000250|UniProtKB:Q62735, ECO:0000269|PubMed:10334992, ECO:0000269|PubMed:10334993, ECO:0000269|PubMed:10514450, ECO:0000269|PubMed:11579204, ECO:0000269|PubMed:11927623, ECO:0000269|PubMed:12554753, ECO:0000269|PubMed:12660231, ECO:0000269|PubMed:12718892, ECO:0000269|PubMed:12754200, ECO:0000269|PubMed:12806625, ECO:0000269|PubMed:12815072, ECO:0000269|PubMed:12891557, ECO:0000269|PubMed:14684751, ECO:0000269|PubMed:15239098, ECO:0000269|PubMed:15337761, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16269519, ECO:0000269|PubMed:16946559, ECO:0000269|PubMed:17895379, ECO:0000269|PubMed:18621523, ECO:0000269|PubMed:19085950, ECO:0000269|PubMed:19410460, ECO:0000269|PubMed:19586769, ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20447400, ECO:0000269|PubMed:21242261, ECO:0000269|PubMed:21804189, ECO:0000269|PubMed:23928191, ECO:0000305|PubMed:21383957, ECO:0000305|PubMed:22820415}.; FUNCTION: [Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191}.; FUNCTION: [Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA. {ECO:0000269|PubMed:23928191, ECO:0000269|PubMed:26888176}. |
| Q13287 | NMI | T229 | Sugiyama | N-myc-interactor (Nmi) (N-myc and STAT interactor) | Acts as a signaling pathway regulator involved in innate immune system response (PubMed:26342464, PubMed:29038465, PubMed:29350881, PubMed:9989503). In response to interleukin 2/IL2 and interferon IFN-gamma/IFNG, interacts with signal transducer and activator of transcription/STAT which activate the transcription of downstream genes involved in a multitude of signals for development and homeostasis (PubMed:29377960, PubMed:9989503). Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, resulting in increased STAT1- and STAT5-dependent transcription (PubMed:9989503). In response to interferon IFN-alpha, associates in a complex with signaling pathway regulator IFI35 to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 (PubMed:10779520, PubMed:10950963). In complex with IFI35, inhibits virus-triggered type I IFN-beta production when ubiquitinated by ubiquitin-protein ligase TRIM21 (PubMed:26342464). In complex with IFI35, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries (PubMed:29350881). Negatively regulates virus-triggered type I interferon/IFN production by inducing proteosome-dependent degradation of IRF7, a transcriptional regulator of type I IFN, thereby interfering with cellular antiviral responses (By similarity). Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation, when actively released by macrophage to the extracellular space during cell injury or pathogen invasion (PubMed:29038465). Macrophage-secreted NMI activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 binding and activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines (PubMed:29038465). {ECO:0000250|UniProtKB:O35309, ECO:0000269|PubMed:10779520, ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:26342464, ECO:0000269|PubMed:29038465, ECO:0000269|PubMed:29350881, ECO:0000269|PubMed:9989503}. |
| P46940 | IQGAP1 | T1471 | Sugiyama | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| Q12851 | MAP4K2 | T63 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
| P30626 | SRI | T130 | Sugiyama | Sorcin (22 kDa protein) (CP-22) (CP22) (V19) | Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the heart sarcoplasmic reticulum. Modulates the activity of RYR2 calcium channels. {ECO:0000269|PubMed:17699613}. |
| P33316 | DUT | T124 | Sugiyama | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial (dUTPase) (EC 3.6.1.23) (dUTP pyrophosphatase) | Catalyzes the cleavage of 2'-deoxyuridine 5'-triphosphate (dUTP) into 2'-deoxyuridine 5'-monophosphate (dUMP) and inorganic pyrophosphate and through its action efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo thymidylate biosynthesis (PubMed:17880943, PubMed:8631816, PubMed:8805593). Inhibits peroxisome proliferator-activated receptor (PPAR) activity by binding of its N-terminal to PPAR, preventing the latter's dimerization with retinoid X receptor (By similarity). Essential for embryonic development (By similarity). {ECO:0000250|UniProtKB:P70583, ECO:0000250|UniProtKB:Q9CQ43, ECO:0000269|PubMed:17880943, ECO:0000269|PubMed:8631816, ECO:0000269|PubMed:8805593}. |
| Q13347 | EIF3I | T201 | Sugiyama | Eukaryotic translation initiation factor 3 subunit I (eIF3i) (Eukaryotic translation initiation factor 3 subunit 2) (TGF-beta receptor-interacting protein 1) (TRIP-1) (eIF-3-beta) (eIF3 p36) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03008, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| O15212 | PFDN6 | T38 | Sugiyama | Prefoldin subunit 6 (Protein Ke2) | Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. {ECO:0000269|PubMed:9630229}. |
| Q14289 | PTK2B | T149 | Sugiyama | Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) | Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. |
| O60551 | NMT2 | T176 | Sugiyama | Glycylpeptide N-tetradecanoyltransferase 2 (EC 2.3.1.97) (Myristoyl-CoA:protein N-myristoyltransferase 2) (NMT 2) (Peptide N-myristoyltransferase 2) (Protein-lysine myristoyltransferase NMT2) (EC 2.3.1.-) (Type II N-myristoyltransferase) | Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins (PubMed:25255805, PubMed:9506952). Also able to mediate N-terminal lysine myristoylation of proteins: catalyzes myristoylation of ARF6 on both 'Gly-2' and 'Lys-3' (PubMed:32103017). Lysine myristoylation is required to maintain ARF6 on membranes during the GTPase cycle (PubMed:32103017). {ECO:0000269|PubMed:25255805, ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:9506952}. |
| P30419 | NMT1 | T174 | Sugiyama | Glycylpeptide N-tetradecanoyltransferase 1 (EC 2.3.1.97) (Myristoyl-CoA:protein N-myristoyltransferase 1) (HsNMT1) (NMT 1) (Type I N-myristoyltransferase) (Peptide N-myristoyltransferase 1) (Protein-lysine myristoyltransferase NMT1) (EC 2.3.1.-) | Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins (PubMed:22865860, PubMed:25255805, PubMed:32686708, PubMed:34999170, PubMed:9353336, PubMed:9506952). Also able to mediate N-terminal lysine myristoylation of proteins: catalyzes myristoylation of ARF6 on both 'Gly-2' and 'Lys-3' (PubMed:32103017, PubMed:32111831). Lysine myristoylation is required to maintain ARF6 on membranes during the GTPase cycle (PubMed:32103017). {ECO:0000269|PubMed:22865860, ECO:0000269|PubMed:25255805, ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:32111831, ECO:0000269|PubMed:32686708, ECO:0000269|PubMed:34999170, ECO:0000269|PubMed:9353336, ECO:0000269|PubMed:9506952}. |
| P07900 | HSP90AA1 | T94 | Sugiyama | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| Q58FG1 | HSP90AA4P | T34 | Sugiyama | Putative heat shock protein HSP 90-alpha A4 (Heat shock 90 kDa protein 1 alpha-like 2) (Heat shock protein 90-alpha D) (Heat shock protein 90Ad) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| O94776 | MTA2 | T621 | Sugiyama | Metastasis-associated protein MTA2 (Metastasis-associated 1-like 1) (MTA1-L1 protein) (p53 target protein in deacetylase complex) | May function as a transcriptional coregulator (PubMed:16428440, PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| Q96EK9 | KTI12 | T157 | Sugiyama | Protein KTI12 homolog | None |
| Q14155 | ARHGEF7 | T127 | SIGNOR | Rho guanine nucleotide exchange factor 7 (Beta-Pix) (COOL-1) (PAK-interacting exchange factor beta) (p85) | Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons. {ECO:0000250, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750}. |
| Q5S007 | LRRK2 | T826 | EPSD|PSP | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q8IWI9 | MGA | T862 | Sugiyama | MAX gene-associated protein (MAX dimerization protein 5) | Functions as a dual-specificity transcription factor, regulating the expression of both MAX-network and T-box family target genes. Functions as a repressor or an activator. Binds to 5'-AATTTCACACCTAGGTGTGAAATT-3' core sequence and seems to regulate MYC-MAX target genes. Suppresses transcriptional activation by MYC and inhibits MYC-dependent cell transformation. Function activated by heterodimerization with MAX. This heterodimerization serves the dual function of both generating an E-box-binding heterodimer and simultaneously blocking interaction of a corepressor (By similarity). {ECO:0000250|UniProtKB:A2AWL7}. |
| Q6XUX3 | DSTYK | T436 | Sugiyama | Dual serine/threonine and tyrosine protein kinase (EC 2.7.12.1) (Dusty protein kinase) (Dusty PK) (RIP-homologous kinase) (Receptor-interacting serine/threonine-protein kinase 5) (Sugen kinase 496) (SgK496) | Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}. |
| O75934 | BCAS2 | T40 | Sugiyama | Pre-mRNA-splicing factor SPF27 (Breast carcinoma-amplified sequence 2) (DNA amplified in mammary carcinoma 1 protein) (Spliceosome-associated protein SPF 27) | Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR). {ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30705154}. |
| Q96G46 | DUS3L | T82 | Sugiyama | tRNA-dihydrouridine(47) synthase [NAD(P)(+)]-like (EC 1.3.1.89) (mRNA-dihydrouridine synthase DUS3L) (EC 1.3.1.-) (tRNA-dihydrouridine synthase 3-like) | Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:34556860). Mainly modifies the uridine in position 47 (U47) in the D-loop of most cytoplasmic tRNAs (PubMed:34556860). Also able to mediate the formation of dihydrouridine in some mRNAs, thereby regulating their translation (PubMed:34556860). {ECO:0000269|PubMed:34556860}. |
| P49368 | CCT3 | T471 | Sugiyama | T-complex protein 1 subunit gamma (TCP-1-gamma) (EC 3.6.1.-) (CCT-gamma) (Chaperonin containing T-complex polypeptide 1 subunit 3) (hTRiC5) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q13200 | PSMD2 | T709 | Sugiyama | 26S proteasome non-ATPase regulatory subunit 2 (26S proteasome regulatory subunit RPN1) (26S proteasome regulatory subunit S2) (26S proteasome subunit p97) (Protein 55.11) (Tumor necrosis factor type 1 receptor-associated protein 2) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}.; FUNCTION: Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1. |
| Q8N568 | DCLK2 | T220 | 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}. |
| Q9BT09 | CNPY3 | T204 | Sugiyama | Protein canopy homolog 3 (CTG repeat protein 4a) (Expanded repeat-domain protein CAG/CTG 5) (Protein associated with TLR4) (Trinucleotide repeat-containing gene 5 protein) | Toll-like receptor (TLR)-specific co-chaperone for HSP90B1. Required for proper TLR folding, except that of TLR3, and hence controls TLR exit from the endoplasmic reticulum. Consequently, required for both innate and adaptive immune responses (By similarity). {ECO:0000250}. |
| Q9H2G2 | SLK | T527 | Sugiyama | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q8TD08 | MAPK15 | T150 | Sugiyama | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| Q92974 | ARHGEF2 | T914 | Sugiyama | Rho guanine nucleotide exchange factor 2 (Guanine nucleotide exchange factor H1) (GEF-H1) (Microtubule-regulated Rho-GEF) (Proliferating cell nucleolar antigen p40) | Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (By similarity). Involved in neuronal progenitor cell division and differentiation (PubMed:28453519). Involved in the migration of precerebellar neurons (By similarity). {ECO:0000250|UniProtKB:Q60875, ECO:0000250|UniProtKB:Q865S3, ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:28453519, ECO:0000269|PubMed:9857026}. |
| Q92522 | H1-10 | T101 | Sugiyama | Histone H1.10 (Histone H1x) | Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. |
| Q9BWD1 | ACAT2 | T218 | Sugiyama | Acetyl-CoA acetyltransferase, cytosolic (EC 2.3.1.9) (Acetyl-CoA transferase-like protein) (Cytosolic acetoacetyl-CoA thiolase) | Involved in the biosynthetic pathway of cholesterol. {ECO:0000303|PubMed:15733928}. |
| Q15459 | SF3A1 | T474 | Sugiyama | Splicing factor 3A subunit 1 (SF3a120) (Spliceosome-associated protein 114) (SAP 114) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:10882114, PubMed:11533230, PubMed:32494006). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:10882114, PubMed:11533230, PubMed:32494006). Within the 17S U2 SnRNP complex, SF3A1 is part of the SF3A subcomplex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex (PubMed:10882114, PubMed:11533230). Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes (PubMed:29360106, PubMed:30315277). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:11533230, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:32494006}. |
| Q9ULF5 | SLC39A10 | T87 | Sugiyama | Zinc transporter ZIP10 (Solute carrier family 39 member 10) (Zrt- and Irt-like protein 10) (ZIP-10) | Zinc-influx transporter (PubMed:17359283, PubMed:27274087, PubMed:30520657). When associated with SLC39A6, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT) (PubMed:23186163). SLC39A10-SLC39A6 heterodimers play also an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (PubMed:32797246). Plays an important for both mature B-cell maintenance and humoral immune responses (By similarity). When associated with SLC39A10, the heterodimer controls NCAM1 phosphorylation and integration into focal adhesion complexes during EMT (By similarity). {ECO:0000250|UniProtKB:Q6P5F6, ECO:0000269|PubMed:17359283, ECO:0000269|PubMed:23186163, ECO:0000269|PubMed:27274087, ECO:0000269|PubMed:30520657, ECO:0000269|PubMed:32797246}. |
| P06733 | ENO1 | T229 | Sugiyama | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P12109 | COL6A1 | T205 | Sugiyama | Collagen alpha-1(VI) chain | Collagen VI acts as a cell-binding protein. |
| P48454 | PPP3CC | T157 | Sugiyama | Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform (EC 3.1.3.16) (CAM-PRP catalytic subunit) (Calcineurin, testis-specific catalytic subunit) (Calmodulin-dependent calcineurin A subunit gamma isoform) | Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32. {ECO:0000269|PubMed:19154138}. |
| Q99700 | ATXN2 | T811 | Sugiyama | Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) | Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}. |
| Q9H2X6 | HIPK2 | T961 | Sugiyama | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| Q9NQU5 | PAK6 | T382 | Sugiyama | Serine/threonine-protein kinase PAK 6 (EC 2.7.11.1) (PAK-5) (p21-activated kinase 6) (PAK-6) | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Also inhibits ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}. |
| Q9NWZ3 | IRAK4 | T324 | Sugiyama | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| P47712 | PLA2G4A | T426 | Sugiyama | Cytosolic phospholipase A2 (cPLA2) (Phospholipase A2 group IVA) [Includes: Phospholipase A2 (EC 3.1.1.4) (Phosphatidylcholine 2-acylhydrolase); Lysophospholipase (EC 3.1.1.5)] | Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891). {ECO:0000250|UniProtKB:P47713, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:12672805, ECO:0000269|PubMed:14709560, ECO:0000269|PubMed:16617059, ECO:0000269|PubMed:17472963, ECO:0000269|PubMed:18451993, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7794891, ECO:0000269|PubMed:8619991, ECO:0000269|PubMed:8702602, ECO:0000269|PubMed:9425121}. |
| P13796 | LCP1 | T174 | Sugiyama | Plastin-2 (L-plastin) (LC64P) (Lymphocyte cytosolic protein 1) (LCP-1) | Actin-binding protein (PubMed:16636079, PubMed:17294403, PubMed:28493397). Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28 (PubMed:17294403). Modulates the cell surface expression of IL2RA/CD25 and CD69 (PubMed:17294403). {ECO:0000269|PubMed:16636079, ECO:0000269|PubMed:17294403, ECO:0000269|PubMed:28493397}. |
| P13797 | PLS3 | T177 | Sugiyama | Plastin-3 (T-fimbrin) (T-plastin) | Actin-bundling protein. |
| Q32MZ4 | LRRFIP1 | T477 | Sugiyama | Leucine-rich repeat flightless-interacting protein 1 (LRR FLII-interacting protein 1) (GC-binding factor 2) (TAR RNA-interacting protein) | Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:10364563, ECO:0000269|PubMed:14522076, ECO:0000269|PubMed:16199883, ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:9705290}. |
| Q9P2E9 | RRBP1 | T1306 | Sugiyama | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| Q52LJ0 | FAM98B | T265 | Sugiyama | Protein FAM98B | Positively stimulates PRMT1-induced protein arginine dimethylated arginine methylation (PubMed:28040436). {ECO:0000269|PubMed:28040436}. |
| Q9NR30 | DDX21 | T377 | Sugiyama | Nucleolar RNA helicase 2 (EC 3.6.4.13) (DEAD box protein 21) (Gu-alpha) (Nucleolar RNA helicase Gu) (Nucleolar RNA helicase II) (RH II/Gu) | RNA helicase that acts as a sensor of the transcriptional status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA (rRNA) processing and transcription from polymerase II (Pol II) (PubMed:25470060, PubMed:28790157). Binds various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs (PubMed:25470060). In the nucleolus, localizes to rDNA locus, where it directly binds rRNAs and snoRNAs, and promotes rRNA transcription, processing and modification. Required for rRNA 2'-O-methylation, possibly by promoting the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-ribosomal complexes (PubMed:25470060, PubMed:25477391). In the nucleoplasm, binds 7SK RNA and is recruited to the promoters of Pol II-transcribed genes: acts by facilitating the release of P-TEFb from inhibitory 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes (PubMed:25470060). Functions as a cofactor for JUN-activated transcription: required for phosphorylation of JUN at 'Ser-77' (PubMed:11823437, PubMed:25260534). Can unwind double-stranded RNA (helicase) and can fold or introduce a secondary structure to a single-stranded RNA (foldase) (PubMed:9461305). Together with SIRT7, required to prevent R-loop-associated DNA damage and transcription-associated genomic instability: deacetylation by SIRT7 activates the helicase activity, thereby overcoming R-loop-mediated stalling of RNA polymerases (PubMed:28790157). Involved in rRNA processing (PubMed:14559904, PubMed:18180292). May bind to specific miRNA hairpins (PubMed:28431233). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity). {ECO:0000250|UniProtKB:Q9JIK5, ECO:0000269|PubMed:11823437, ECO:0000269|PubMed:14559904, ECO:0000269|PubMed:18180292, ECO:0000269|PubMed:25260534, ECO:0000269|PubMed:25470060, ECO:0000269|PubMed:25477391, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:9461305}. |
| Q9Y4K4 | MAP4K5 | T827 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 5 (EC 2.7.11.1) (Kinase homologous to SPS1/STE20) (KHS) (MAPK/ERK kinase kinase kinase 5) (MEK kinase kinase 5) (MEKKK 5) | May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. {ECO:0000269|PubMed:9038372}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 1.110223e-16 | 15.955 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 1.110223e-16 | 15.955 |
| R-HSA-422475 | Axon guidance | 1.110223e-16 | 15.955 |
| R-HSA-9675108 | Nervous system development | 1.110223e-16 | 15.955 |
| R-HSA-162582 | Signal Transduction | 1.110223e-16 | 15.955 |
| R-HSA-5683057 | MAPK family signaling cascades | 1.221245e-15 | 14.913 |
| R-HSA-2682334 | EPH-Ephrin signaling | 3.552714e-15 | 14.449 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 1.054712e-14 | 13.977 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 1.243450e-14 | 13.905 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 2.176037e-13 | 12.662 |
| R-HSA-109581 | Apoptosis | 2.485789e-13 | 12.605 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 2.844391e-13 | 12.546 |
| R-HSA-5357801 | Programmed Cell Death | 8.575363e-13 | 12.067 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 1.183054e-12 | 11.927 |
| R-HSA-373760 | L1CAM interactions | 3.700595e-12 | 11.432 |
| R-HSA-2467813 | Separation of Sister Chromatids | 5.070833e-12 | 11.295 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 1.080736e-11 | 10.966 |
| R-HSA-8953897 | Cellular responses to stimuli | 1.377787e-11 | 10.861 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 2.100708e-11 | 10.678 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 2.524592e-11 | 10.598 |
| R-HSA-9646399 | Aggrephagy | 2.912548e-11 | 10.536 |
| R-HSA-2262752 | Cellular responses to stress | 3.977263e-11 | 10.400 |
| R-HSA-437239 | Recycling pathway of L1 | 7.875378e-11 | 10.104 |
| R-HSA-9663891 | Selective autophagy | 7.983780e-11 | 10.098 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 9.533174e-11 | 10.021 |
| R-HSA-68882 | Mitotic Anaphase | 1.508570e-10 | 9.821 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 1.726708e-10 | 9.763 |
| R-HSA-69275 | G2/M Transition | 1.956267e-10 | 9.709 |
| R-HSA-449147 | Signaling by Interleukins | 2.071975e-10 | 9.684 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 2.614774e-10 | 9.583 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 3.339925e-10 | 9.476 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 4.774294e-10 | 9.321 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 5.475732e-10 | 9.262 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 1.017007e-09 | 8.993 |
| R-HSA-9764561 | Regulation of CDH1 Function | 1.653801e-09 | 8.782 |
| R-HSA-1640170 | Cell Cycle | 1.827158e-09 | 8.738 |
| R-HSA-1227986 | Signaling by ERBB2 | 3.693797e-09 | 8.433 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 4.344280e-09 | 8.362 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 6.730068e-09 | 8.172 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 6.707372e-09 | 8.173 |
| R-HSA-9612973 | Autophagy | 8.140571e-09 | 8.089 |
| R-HSA-1632852 | Macroautophagy | 8.248815e-09 | 8.084 |
| R-HSA-69620 | Cell Cycle Checkpoints | 8.633864e-09 | 8.064 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 1.060654e-08 | 7.974 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 1.123952e-08 | 7.949 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1.221455e-08 | 7.913 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.276319e-08 | 7.894 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.506245e-08 | 7.822 |
| R-HSA-69278 | Cell Cycle, Mitotic | 2.514186e-08 | 7.600 |
| R-HSA-68886 | M Phase | 2.525380e-08 | 7.598 |
| R-HSA-69481 | G2/M Checkpoints | 2.702301e-08 | 7.568 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 3.081585e-08 | 7.511 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 4.090395e-08 | 7.388 |
| R-HSA-68877 | Mitotic Prometaphase | 4.305877e-08 | 7.366 |
| R-HSA-168256 | Immune System | 4.453133e-08 | 7.351 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.195813e-08 | 7.208 |
| R-HSA-75153 | Apoptotic execution phase | 6.100556e-08 | 7.215 |
| R-HSA-194138 | Signaling by VEGF | 6.683095e-08 | 7.175 |
| R-HSA-983189 | Kinesins | 8.506977e-08 | 7.070 |
| R-HSA-9700206 | Signaling by ALK in cancer | 9.902563e-08 | 7.004 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 9.902563e-08 | 7.004 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 1.174900e-07 | 6.930 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 1.174900e-07 | 6.930 |
| R-HSA-157858 | Gap junction trafficking and regulation | 1.338500e-07 | 6.873 |
| R-HSA-199991 | Membrane Trafficking | 1.565686e-07 | 6.805 |
| R-HSA-190828 | Gap junction trafficking | 1.838786e-07 | 6.735 |
| R-HSA-1266738 | Developmental Biology | 2.277841e-07 | 6.642 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 2.304037e-07 | 6.638 |
| R-HSA-9833482 | PKR-mediated signaling | 3.049590e-07 | 6.516 |
| R-HSA-438064 | Post NMDA receptor activation events | 3.427876e-07 | 6.465 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 3.534550e-07 | 6.452 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 4.085152e-07 | 6.389 |
| R-HSA-6807070 | PTEN Regulation | 6.234214e-07 | 6.205 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 6.082443e-07 | 6.216 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 7.023787e-07 | 6.153 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 7.405040e-07 | 6.130 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 7.534199e-07 | 6.123 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 9.117343e-07 | 6.040 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 9.196337e-07 | 6.036 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 9.809859e-07 | 6.008 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 1.086306e-06 | 5.964 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 1.251219e-06 | 5.903 |
| R-HSA-6798695 | Neutrophil degranulation | 1.508999e-06 | 5.821 |
| R-HSA-9013694 | Signaling by NOTCH4 | 1.496049e-06 | 5.825 |
| R-HSA-162909 | Host Interactions of HIV factors | 1.627157e-06 | 5.789 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 1.710042e-06 | 5.767 |
| R-HSA-114452 | Activation of BH3-only proteins | 1.710042e-06 | 5.767 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 1.978694e-06 | 5.704 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 2.270510e-06 | 5.644 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 2.296434e-06 | 5.639 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 2.420812e-06 | 5.616 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 2.758221e-06 | 5.559 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 2.675712e-06 | 5.573 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 3.054818e-06 | 5.515 |
| R-HSA-391251 | Protein folding | 3.258706e-06 | 5.487 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 3.369352e-06 | 5.472 |
| R-HSA-2428924 | IGF1R signaling cascade | 3.519939e-06 | 5.453 |
| R-HSA-5610787 | Hedgehog 'off' state | 3.764160e-06 | 5.424 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 4.239548e-06 | 5.373 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 5.006127e-06 | 5.300 |
| R-HSA-3928664 | Ephrin signaling | 5.440907e-06 | 5.264 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 6.166198e-06 | 5.210 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 6.825744e-06 | 5.166 |
| R-HSA-190861 | Gap junction assembly | 6.825744e-06 | 5.166 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 7.262102e-06 | 5.139 |
| R-HSA-9607240 | FLT3 Signaling | 7.786062e-06 | 5.109 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 7.786062e-06 | 5.109 |
| R-HSA-912631 | Regulation of signaling by CBL | 7.840899e-06 | 5.106 |
| R-HSA-190236 | Signaling by FGFR | 9.049773e-06 | 5.043 |
| R-HSA-169911 | Regulation of Apoptosis | 8.782295e-06 | 5.056 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 9.325693e-06 | 5.030 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 9.686266e-06 | 5.014 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 9.772102e-06 | 5.010 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 9.901464e-06 | 5.004 |
| R-HSA-389356 | Co-stimulation by CD28 | 1.011206e-05 | 4.995 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 1.023508e-05 | 4.990 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 1.110527e-05 | 4.954 |
| R-HSA-5617833 | Cilium Assembly | 1.092933e-05 | 4.961 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 1.121695e-05 | 4.950 |
| R-HSA-8848021 | Signaling by PTK6 | 1.124163e-05 | 4.949 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 1.124163e-05 | 4.949 |
| R-HSA-9711123 | Cellular response to chemical stress | 1.140872e-05 | 4.943 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 1.289190e-05 | 4.890 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 1.289190e-05 | 4.890 |
| R-HSA-9766229 | Degradation of CDH1 | 1.239822e-05 | 4.907 |
| R-HSA-2132295 | MHC class II antigen presentation | 1.244973e-05 | 4.905 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 1.209680e-05 | 4.917 |
| R-HSA-4641258 | Degradation of DVL | 1.422649e-05 | 4.847 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 1.425620e-05 | 4.846 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 1.462801e-05 | 4.835 |
| R-HSA-109704 | PI3K Cascade | 1.513149e-05 | 4.820 |
| R-HSA-168249 | Innate Immune System | 1.580110e-05 | 4.801 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 1.757924e-05 | 4.755 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 2.243638e-05 | 4.649 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 2.171333e-05 | 4.663 |
| R-HSA-68949 | Orc1 removal from chromatin | 2.224371e-05 | 4.653 |
| R-HSA-69541 | Stabilization of p53 | 2.243638e-05 | 4.649 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 2.143693e-05 | 4.669 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 2.143693e-05 | 4.669 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 2.293019e-05 | 4.640 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 2.293019e-05 | 4.640 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 2.194726e-05 | 4.659 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 2.448308e-05 | 4.611 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 2.597137e-05 | 4.586 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 2.801610e-05 | 4.553 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 2.801610e-05 | 4.553 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 2.801610e-05 | 4.553 |
| R-HSA-6802949 | Signaling by RAS mutants | 2.801610e-05 | 4.553 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 3.286837e-05 | 4.483 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 3.286837e-05 | 4.483 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 3.452770e-05 | 4.462 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 3.452770e-05 | 4.462 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 3.340259e-05 | 4.476 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 3.286837e-05 | 4.483 |
| R-HSA-9664873 | Pexophagy | 3.695556e-05 | 4.432 |
| R-HSA-373755 | Semaphorin interactions | 4.103944e-05 | 4.387 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 4.130214e-05 | 4.384 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 4.130214e-05 | 4.384 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 4.246804e-05 | 4.372 |
| R-HSA-202403 | TCR signaling | 4.784274e-05 | 4.320 |
| R-HSA-74751 | Insulin receptor signalling cascade | 4.825955e-05 | 4.316 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 5.154945e-05 | 4.288 |
| R-HSA-9824446 | Viral Infection Pathways | 5.190326e-05 | 4.285 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 5.825805e-05 | 4.235 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 5.825805e-05 | 4.235 |
| R-HSA-112399 | IRS-mediated signalling | 5.432293e-05 | 4.265 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 5.825805e-05 | 4.235 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 6.281197e-05 | 4.202 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 6.322979e-05 | 4.199 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 6.392469e-05 | 4.194 |
| R-HSA-4641257 | Degradation of AXIN | 6.392469e-05 | 4.194 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 6.392469e-05 | 4.194 |
| R-HSA-373753 | Nephrin family interactions | 6.729312e-05 | 4.172 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 7.123895e-05 | 4.147 |
| R-HSA-8948747 | Regulation of PTEN localization | 7.388172e-05 | 4.131 |
| R-HSA-5653656 | Vesicle-mediated transport | 7.858602e-05 | 4.105 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 8.478437e-05 | 4.072 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 8.478437e-05 | 4.072 |
| R-HSA-9948299 | Ribosome-associated quality control | 8.801347e-05 | 4.055 |
| R-HSA-376176 | Signaling by ROBO receptors | 8.032845e-05 | 4.095 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 8.377051e-05 | 4.077 |
| R-HSA-1500931 | Cell-Cell communication | 7.948021e-05 | 4.100 |
| R-HSA-5358351 | Signaling by Hedgehog | 8.801347e-05 | 4.055 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 8.960385e-05 | 4.048 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 8.960385e-05 | 4.048 |
| R-HSA-5654741 | Signaling by FGFR3 | 9.228623e-05 | 4.035 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 9.228623e-05 | 4.035 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 9.228623e-05 | 4.035 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 9.228623e-05 | 4.035 |
| R-HSA-201556 | Signaling by ALK | 9.652419e-05 | 4.015 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 1.005160e-04 | 3.998 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 1.005160e-04 | 3.998 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 1.040536e-04 | 3.983 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 1.107152e-04 | 3.956 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 1.155117e-04 | 3.937 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 1.175949e-04 | 3.930 |
| R-HSA-9706377 | FLT3 signaling by CBL mutants | 1.328412e-04 | 3.877 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 1.322368e-04 | 3.879 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 1.322368e-04 | 3.879 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 1.236453e-04 | 3.908 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 1.199842e-04 | 3.921 |
| R-HSA-69206 | G1/S Transition | 1.273519e-04 | 3.895 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 1.248019e-04 | 3.904 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 1.328535e-04 | 3.877 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 1.397187e-04 | 3.855 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 1.401214e-04 | 3.853 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 1.412767e-04 | 3.850 |
| R-HSA-5654738 | Signaling by FGFR2 | 1.509091e-04 | 3.821 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 1.638539e-04 | 3.786 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 1.638539e-04 | 3.786 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 1.640096e-04 | 3.785 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.717710e-04 | 3.765 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 1.717710e-04 | 3.765 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 1.717710e-04 | 3.765 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 1.717710e-04 | 3.765 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 1.717710e-04 | 3.765 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 1.717710e-04 | 3.765 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 1.824565e-04 | 3.739 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 1.862704e-04 | 3.730 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 1.862704e-04 | 3.730 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 1.895620e-04 | 3.722 |
| R-HSA-1234174 | Cellular response to hypoxia | 1.895620e-04 | 3.722 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 2.186529e-04 | 3.660 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 2.032896e-04 | 3.692 |
| R-HSA-1226099 | Signaling by FGFR in disease | 2.087859e-04 | 3.680 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 1.998906e-04 | 3.699 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 2.132230e-04 | 3.671 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 2.132230e-04 | 3.671 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 2.197450e-04 | 3.658 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 2.202053e-04 | 3.657 |
| R-HSA-8953854 | Metabolism of RNA | 2.213273e-04 | 3.655 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 2.383518e-04 | 3.623 |
| R-HSA-69242 | S Phase | 2.452646e-04 | 3.610 |
| R-HSA-162906 | HIV Infection | 2.454528e-04 | 3.610 |
| R-HSA-5654743 | Signaling by FGFR4 | 2.459657e-04 | 3.609 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 2.493428e-04 | 3.603 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 2.582424e-04 | 3.588 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 2.582424e-04 | 3.588 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 2.658399e-04 | 3.575 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 2.699055e-04 | 3.569 |
| R-HSA-5689603 | UCH proteinases | 2.714789e-04 | 3.566 |
| R-HSA-69236 | G1 Phase | 2.922876e-04 | 3.534 |
| R-HSA-69231 | Cyclin D associated events in G1 | 2.922876e-04 | 3.534 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 2.922876e-04 | 3.534 |
| R-HSA-9020702 | Interleukin-1 signaling | 3.218777e-04 | 3.492 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 3.461287e-04 | 3.461 |
| R-HSA-450294 | MAP kinase activation | 3.461287e-04 | 3.461 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 3.461287e-04 | 3.461 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 3.462959e-04 | 3.461 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 3.467108e-04 | 3.460 |
| R-HSA-4086400 | PCP/CE pathway | 3.498379e-04 | 3.456 |
| R-HSA-193639 | p75NTR signals via NF-kB | 3.719681e-04 | 3.429 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 3.983258e-04 | 3.400 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 4.000080e-04 | 3.398 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 4.099289e-04 | 3.387 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 4.101145e-04 | 3.387 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 4.292296e-04 | 3.367 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 4.292296e-04 | 3.367 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 4.385207e-04 | 3.358 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 4.570981e-04 | 3.340 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 4.570981e-04 | 3.340 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 4.752181e-04 | 3.323 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 4.752181e-04 | 3.323 |
| R-HSA-3371556 | Cellular response to heat stress | 4.936268e-04 | 3.307 |
| R-HSA-1643685 | Disease | 4.976737e-04 | 3.303 |
| R-HSA-9706369 | Negative regulation of FLT3 | 5.027991e-04 | 3.299 |
| R-HSA-1236974 | ER-Phagosome pathway | 5.077298e-04 | 3.294 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 5.097297e-04 | 3.293 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 5.231998e-04 | 3.281 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 5.444840e-04 | 3.264 |
| R-HSA-5654736 | Signaling by FGFR1 | 5.488527e-04 | 3.261 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 5.488527e-04 | 3.261 |
| R-HSA-5620924 | Intraflagellar transport | 5.586173e-04 | 3.253 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 5.663998e-04 | 3.247 |
| R-HSA-202424 | Downstream TCR signaling | 5.673648e-04 | 3.246 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 6.678847e-04 | 3.175 |
| R-HSA-9909396 | Circadian clock | 6.630952e-04 | 3.178 |
| R-HSA-5633007 | Regulation of TP53 Activity | 6.630409e-04 | 3.178 |
| R-HSA-913531 | Interferon Signaling | 5.808482e-04 | 3.236 |
| R-HSA-209560 | NF-kB is activated and signals survival | 6.336316e-04 | 3.198 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 6.195918e-04 | 3.208 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 6.195918e-04 | 3.208 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 6.195918e-04 | 3.208 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 6.431748e-04 | 3.192 |
| R-HSA-157118 | Signaling by NOTCH | 5.878156e-04 | 3.231 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 6.866187e-04 | 3.163 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 5.970354e-04 | 3.224 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 7.278667e-04 | 3.138 |
| R-HSA-5688426 | Deubiquitination | 7.627877e-04 | 3.118 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 7.649947e-04 | 3.116 |
| R-HSA-397014 | Muscle contraction | 7.654001e-04 | 3.116 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 7.692670e-04 | 3.114 |
| R-HSA-9615710 | Late endosomal microautophagy | 7.692670e-04 | 3.114 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 7.709500e-04 | 3.113 |
| R-HSA-74752 | Signaling by Insulin receptor | 7.836900e-04 | 3.106 |
| R-HSA-9020591 | Interleukin-12 signaling | 7.938393e-04 | 3.100 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 7.963405e-04 | 3.099 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 8.011183e-04 | 3.096 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 8.146504e-04 | 3.089 |
| R-HSA-211163 | AKT-mediated inactivation of FOXO1A | 8.146504e-04 | 3.089 |
| R-HSA-9679506 | SARS-CoV Infections | 8.412270e-04 | 3.075 |
| R-HSA-114604 | GPVI-mediated activation cascade | 8.577084e-04 | 3.067 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 8.699306e-04 | 3.061 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 8.732435e-04 | 3.059 |
| R-HSA-2028269 | Signaling by Hippo | 8.732435e-04 | 3.059 |
| R-HSA-5689880 | Ub-specific processing proteases | 8.791806e-04 | 3.056 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 8.791806e-04 | 3.056 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 8.791806e-04 | 3.056 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 8.819832e-04 | 3.055 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 8.819832e-04 | 3.055 |
| R-HSA-8866427 | VLDLR internalisation and degradation | 8.819832e-04 | 3.055 |
| R-HSA-2424491 | DAP12 signaling | 9.345301e-04 | 3.029 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 9.555604e-04 | 3.020 |
| R-HSA-8939211 | ESR-mediated signaling | 9.588511e-04 | 3.018 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 1.017127e-03 | 2.993 |
| R-HSA-447115 | Interleukin-12 family signaling | 1.101336e-03 | 2.958 |
| R-HSA-448424 | Interleukin-17 signaling | 1.113593e-03 | 2.953 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 1.127492e-03 | 2.948 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 1.160938e-03 | 2.935 |
| R-HSA-9824272 | Somitogenesis | 1.200425e-03 | 2.921 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 1.252568e-03 | 2.902 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 1.266396e-03 | 2.897 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.354436e-03 | 2.868 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 1.388911e-03 | 2.857 |
| R-HSA-9818025 | NFE2L2 regulating TCA cycle genes | 1.431185e-03 | 2.844 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 1.450110e-03 | 2.839 |
| R-HSA-9012852 | Signaling by NOTCH3 | 1.506243e-03 | 2.822 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 1.514085e-03 | 2.820 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 1.574306e-03 | 2.803 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 1.574306e-03 | 2.803 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 1.606578e-03 | 2.794 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 1.763846e-03 | 2.754 |
| R-HSA-390522 | Striated Muscle Contraction | 1.906545e-03 | 2.720 |
| R-HSA-1236394 | Signaling by ERBB4 | 1.759339e-03 | 2.755 |
| R-HSA-380287 | Centrosome maturation | 1.962088e-03 | 2.707 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 2.013144e-03 | 2.696 |
| R-HSA-9614085 | FOXO-mediated transcription | 1.731251e-03 | 2.762 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 1.798704e-03 | 2.745 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 1.759339e-03 | 2.755 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 1.954834e-03 | 2.709 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 1.907827e-03 | 2.719 |
| R-HSA-109582 | Hemostasis | 1.759341e-03 | 2.755 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.763846e-03 | 2.754 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 2.080519e-03 | 2.682 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 2.088447e-03 | 2.680 |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment | 2.088447e-03 | 2.680 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 2.088447e-03 | 2.680 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 2.107617e-03 | 2.676 |
| R-HSA-5689877 | Josephin domain DUBs | 2.107617e-03 | 2.676 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 2.115498e-03 | 2.675 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 2.115498e-03 | 2.675 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 2.128880e-03 | 2.672 |
| R-HSA-1280218 | Adaptive Immune System | 2.213462e-03 | 2.655 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 2.240846e-03 | 2.650 |
| R-HSA-5673000 | RAF activation | 2.245303e-03 | 2.649 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 2.304506e-03 | 2.637 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 2.304506e-03 | 2.637 |
| R-HSA-9694493 | Maturation of protein E | 2.315565e-03 | 2.635 |
| R-HSA-9683683 | Maturation of protein E | 2.315565e-03 | 2.635 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 2.332368e-03 | 2.632 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 2.332368e-03 | 2.632 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 2.332368e-03 | 2.632 |
| R-HSA-195721 | Signaling by WNT | 2.389839e-03 | 2.622 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 2.480881e-03 | 2.605 |
| R-HSA-165159 | MTOR signalling | 2.559190e-03 | 2.592 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 2.685797e-03 | 2.571 |
| R-HSA-5619084 | ABC transporter disorders | 2.689600e-03 | 2.570 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 2.749211e-03 | 2.561 |
| R-HSA-210990 | PECAM1 interactions | 2.890046e-03 | 2.539 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 2.890046e-03 | 2.539 |
| R-HSA-9020558 | Interleukin-2 signaling | 2.890046e-03 | 2.539 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 2.927386e-03 | 2.534 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 2.927386e-03 | 2.534 |
| R-HSA-9659379 | Sensory processing of sound | 2.976455e-03 | 2.526 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 3.035413e-03 | 2.518 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 3.035413e-03 | 2.518 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 3.094704e-03 | 2.509 |
| R-HSA-9669938 | Signaling by KIT in disease | 3.349300e-03 | 2.475 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 3.349300e-03 | 2.475 |
| R-HSA-166208 | mTORC1-mediated signalling | 3.349300e-03 | 2.475 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 3.365957e-03 | 2.473 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 3.402798e-03 | 2.468 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 3.402798e-03 | 2.468 |
| R-HSA-5632684 | Hedgehog 'on' state | 3.425460e-03 | 2.465 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 3.475607e-03 | 2.459 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 3.484391e-03 | 2.458 |
| R-HSA-445355 | Smooth Muscle Contraction | 3.497409e-03 | 2.456 |
| R-HSA-164944 | Nef and signal transduction | 3.518170e-03 | 2.454 |
| R-HSA-199920 | CREB phosphorylation | 3.518170e-03 | 2.454 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 3.588799e-03 | 2.445 |
| R-HSA-69239 | Synthesis of DNA | 3.800246e-03 | 2.420 |
| R-HSA-428540 | Activation of RAC1 | 3.863270e-03 | 2.413 |
| R-HSA-72649 | Translation initiation complex formation | 3.941010e-03 | 2.404 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 3.969462e-03 | 2.401 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 4.121651e-03 | 2.385 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 4.121651e-03 | 2.385 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 4.121651e-03 | 2.385 |
| R-HSA-182971 | EGFR downregulation | 4.217204e-03 | 2.375 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 4.217204e-03 | 2.375 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 5.251114e-03 | 2.280 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 4.843515e-03 | 2.315 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 4.962431e-03 | 2.304 |
| R-HSA-177929 | Signaling by EGFR | 4.962431e-03 | 2.304 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 4.499890e-03 | 2.347 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 4.465072e-03 | 2.350 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 5.251114e-03 | 2.280 |
| R-HSA-9842663 | Signaling by LTK | 5.051004e-03 | 2.297 |
| R-HSA-72766 | Translation | 4.504999e-03 | 2.346 |
| R-HSA-168898 | Toll-like Receptor Cascades | 5.640148e-03 | 2.249 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 4.927060e-03 | 2.307 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 4.385540e-03 | 2.358 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 5.086905e-03 | 2.294 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 4.927060e-03 | 2.307 |
| R-HSA-166520 | Signaling by NTRKs | 5.568479e-03 | 2.254 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 4.719996e-03 | 2.326 |
| R-HSA-382556 | ABC-family proteins mediated transport | 4.499890e-03 | 2.347 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 5.035699e-03 | 2.298 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 5.724938e-03 | 2.242 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 5.724938e-03 | 2.242 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 5.829952e-03 | 2.234 |
| R-HSA-9006936 | Signaling by TGFB family members | 5.997032e-03 | 2.222 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 6.182829e-03 | 2.209 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 6.217432e-03 | 2.206 |
| R-HSA-9679191 | Potential therapeutics for SARS | 6.331099e-03 | 2.199 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 6.363571e-03 | 2.196 |
| R-HSA-110320 | Translesion Synthesis by POLH | 6.410466e-03 | 2.193 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 | 6.410466e-03 | 2.193 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 6.476598e-03 | 2.189 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 6.476598e-03 | 2.189 |
| R-HSA-5663205 | Infectious disease | 6.837157e-03 | 2.165 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 6.875422e-03 | 2.163 |
| R-HSA-444257 | RSK activation | 7.066251e-03 | 2.151 |
| R-HSA-196025 | Formation of annular gap junctions | 7.066251e-03 | 2.151 |
| R-HSA-3785653 | Myoclonic epilepsy of Lafora | 7.066251e-03 | 2.151 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 7.066251e-03 | 2.151 |
| R-HSA-9825895 | Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... | 7.066251e-03 | 2.151 |
| R-HSA-9637628 | Modulation by Mtb of host immune system | 7.066251e-03 | 2.151 |
| R-HSA-446652 | Interleukin-1 family signaling | 7.177329e-03 | 2.144 |
| R-HSA-9609690 | HCMV Early Events | 7.449865e-03 | 2.128 |
| R-HSA-6807004 | Negative regulation of MET activity | 7.745288e-03 | 2.111 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 7.958655e-03 | 2.099 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 7.958655e-03 | 2.099 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 7.958655e-03 | 2.099 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 7.965980e-03 | 2.099 |
| R-HSA-73887 | Death Receptor Signaling | 8.113694e-03 | 2.091 |
| R-HSA-6806834 | Signaling by MET | 8.114322e-03 | 2.091 |
| R-HSA-1433559 | Regulation of KIT signaling | 8.162729e-03 | 2.088 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 8.162729e-03 | 2.088 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 8.162729e-03 | 2.088 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 8.162729e-03 | 2.088 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 8.162729e-03 | 2.088 |
| R-HSA-212436 | Generic Transcription Pathway | 8.207973e-03 | 2.086 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 8.356114e-03 | 2.078 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 8.356114e-03 | 2.078 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 8.356114e-03 | 2.078 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 8.356114e-03 | 2.078 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 8.356114e-03 | 2.078 |
| R-HSA-446728 | Cell junction organization | 8.370031e-03 | 2.077 |
| R-HSA-2559585 | Oncogene Induced Senescence | 8.713971e-03 | 2.060 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 8.737538e-03 | 2.059 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 8.737538e-03 | 2.059 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 8.792106e-03 | 2.056 |
| R-HSA-1433557 | Signaling by SCF-KIT | 8.927586e-03 | 2.049 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 8.927586e-03 | 2.049 |
| R-HSA-389948 | Co-inhibition by PD-1 | 9.219694e-03 | 2.035 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 9.267625e-03 | 2.033 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 9.269387e-03 | 2.033 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 9.269387e-03 | 2.033 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 9.496563e-03 | 2.022 |
| R-HSA-190873 | Gap junction degradation | 9.496563e-03 | 2.022 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 9.496563e-03 | 2.022 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 9.496563e-03 | 2.022 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 9.583097e-03 | 2.018 |
| R-HSA-74160 | Gene expression (Transcription) | 9.715090e-03 | 2.013 |
| R-HSA-2172127 | DAP12 interactions | 1.003231e-02 | 1.999 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 1.013113e-02 | 1.994 |
| R-HSA-9027284 | Erythropoietin activates RAS | 1.013113e-02 | 1.994 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 1.013113e-02 | 1.994 |
| R-HSA-8876725 | Protein methylation | 1.013113e-02 | 1.994 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 1.013113e-02 | 1.994 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 1.020935e-02 | 1.991 |
| R-HSA-9006335 | Signaling by Erythropoietin | 1.072750e-02 | 1.970 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 1.072750e-02 | 1.970 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 1.099627e-02 | 1.959 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 1.099627e-02 | 1.959 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 1.168189e-02 | 1.932 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 1.241358e-02 | 1.906 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 1.241358e-02 | 1.906 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 1.242732e-02 | 1.906 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 1.273915e-02 | 1.895 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 1.293903e-02 | 1.888 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1.326309e-02 | 1.877 |
| R-HSA-418990 | Adherens junctions interactions | 1.338412e-02 | 1.873 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 1.377238e-02 | 1.861 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 1.400886e-02 | 1.854 |
| R-HSA-186763 | Downstream signal transduction | 1.413664e-02 | 1.850 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 1.413664e-02 | 1.850 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 1.434276e-02 | 1.843 |
| R-HSA-5693606 | DNA Double Strand Break Response | 1.482612e-02 | 1.829 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 1.499554e-02 | 1.824 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 1.506693e-02 | 1.822 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 1.511025e-02 | 1.821 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.511025e-02 | 1.821 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 1.584813e-02 | 1.800 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 1.584813e-02 | 1.800 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 1.608836e-02 | 1.793 |
| R-HSA-451927 | Interleukin-2 family signaling | 1.608836e-02 | 1.793 |
| R-HSA-156902 | Peptide chain elongation | 1.681508e-02 | 1.774 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 1.715783e-02 | 1.766 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 1.745845e-02 | 1.758 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 1.752190e-02 | 1.756 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 1.765866e-02 | 1.753 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 1.792829e-02 | 1.746 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 1.792829e-02 | 1.746 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 1.798238e-02 | 1.745 |
| R-HSA-5602571 | TRAF3 deficiency - HSE | 1.798533e-02 | 1.745 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 1.804231e-02 | 1.744 |
| R-HSA-168255 | Influenza Infection | 1.824376e-02 | 1.739 |
| R-HSA-354192 | Integrin signaling | 1.825711e-02 | 1.739 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 1.889001e-02 | 1.724 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 1.925565e-02 | 1.715 |
| R-HSA-447043 | Neurofascin interactions | 2.393864e-02 | 1.621 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 2.393864e-02 | 1.621 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 1.982592e-02 | 1.703 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 1.982592e-02 | 1.703 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 2.436755e-02 | 1.613 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 2.436755e-02 | 1.613 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 2.436755e-02 | 1.613 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 2.436755e-02 | 1.613 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 2.436755e-02 | 1.613 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 2.436755e-02 | 1.613 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 2.436755e-02 | 1.613 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 2.487411e-02 | 1.604 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 2.487411e-02 | 1.604 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 2.630812e-02 | 1.580 |
| R-HSA-5696400 | Dual Incision in GG-NER | 2.315525e-02 | 1.635 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 2.591500e-02 | 1.586 |
| R-HSA-8852135 | Protein ubiquitination | 2.827462e-02 | 1.549 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 2.430470e-02 | 1.614 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 2.430470e-02 | 1.614 |
| R-HSA-432142 | Platelet sensitization by LDL | 2.121646e-02 | 1.673 |
| R-HSA-3371511 | HSF1 activation | 2.889112e-02 | 1.539 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 2.315525e-02 | 1.635 |
| R-HSA-9907900 | Proteasome assembly | 2.716415e-02 | 1.566 |
| R-HSA-9682385 | FLT3 signaling in disease | 2.889112e-02 | 1.539 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 2.060506e-02 | 1.686 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 2.472435e-02 | 1.607 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 1.982592e-02 | 1.703 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 2.224041e-02 | 1.653 |
| R-HSA-9664407 | Parasite infection | 2.343067e-02 | 1.630 |
| R-HSA-9664417 | Leishmania phagocytosis | 2.343067e-02 | 1.630 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 2.343067e-02 | 1.630 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 2.675716e-02 | 1.573 |
| R-HSA-69306 | DNA Replication | 2.675716e-02 | 1.573 |
| R-HSA-187687 | Signalling to ERKs | 2.591500e-02 | 1.586 |
| R-HSA-8941326 | RUNX2 regulates bone development | 2.889112e-02 | 1.539 |
| R-HSA-373752 | Netrin-1 signaling | 2.716415e-02 | 1.566 |
| R-HSA-5205647 | Mitophagy | 2.315525e-02 | 1.635 |
| R-HSA-2691232 | Constitutive Signaling by NOTCH1 HD Domain Mutants | 2.436755e-02 | 1.613 |
| R-HSA-2691230 | Signaling by NOTCH1 HD Domain Mutants in Cancer | 2.436755e-02 | 1.613 |
| R-HSA-421270 | Cell-cell junction organization | 2.025853e-02 | 1.693 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 2.747306e-02 | 1.561 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 2.090253e-02 | 1.680 |
| R-HSA-445144 | Signal transduction by L1 | 2.891337e-02 | 1.539 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 2.893058e-02 | 1.539 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 2.930227e-02 | 1.533 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 2.948852e-02 | 1.530 |
| R-HSA-1059683 | Interleukin-6 signaling | 2.948852e-02 | 1.530 |
| R-HSA-170968 | Frs2-mediated activation | 2.948852e-02 | 1.530 |
| R-HSA-73857 | RNA Polymerase II Transcription | 2.966580e-02 | 1.528 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 2.978605e-02 | 1.526 |
| R-HSA-6804754 | Regulation of TP53 Expression | 3.059424e-02 | 1.514 |
| R-HSA-8985801 | Regulation of cortical dendrite branching | 3.059424e-02 | 1.514 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 3.059424e-02 | 1.514 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 3.103610e-02 | 1.508 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 3.103610e-02 | 1.508 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 3.127065e-02 | 1.505 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 3.127065e-02 | 1.505 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 3.127065e-02 | 1.505 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 3.127065e-02 | 1.505 |
| R-HSA-9609646 | HCMV Infection | 3.154152e-02 | 1.501 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 3.208992e-02 | 1.494 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 3.279665e-02 | 1.484 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 3.279665e-02 | 1.484 |
| R-HSA-70268 | Pyruvate metabolism | 3.318267e-02 | 1.479 |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane | 3.334440e-02 | 1.477 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 3.334440e-02 | 1.477 |
| R-HSA-198753 | ERK/MAPK targets | 3.334440e-02 | 1.477 |
| R-HSA-418360 | Platelet calcium homeostasis | 3.355235e-02 | 1.474 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 3.355235e-02 | 1.474 |
| R-HSA-416482 | G alpha (12/13) signalling events | 3.507095e-02 | 1.455 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 3.635669e-02 | 1.439 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 3.647275e-02 | 1.438 |
| R-HSA-5218859 | Regulated Necrosis | 3.681205e-02 | 1.434 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 3.708403e-02 | 1.431 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 3.761381e-02 | 1.425 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 3.817538e-02 | 1.418 |
| R-HSA-175474 | Assembly Of The HIV Virion | 3.817538e-02 | 1.418 |
| R-HSA-9758941 | Gastrulation | 3.891549e-02 | 1.410 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 3.917596e-02 | 1.407 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 3.917805e-02 | 1.407 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 3.917805e-02 | 1.407 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 3.964254e-02 | 1.402 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 3.964254e-02 | 1.402 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 3.964254e-02 | 1.402 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 4.019494e-02 | 1.396 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 4.150598e-02 | 1.382 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 4.150598e-02 | 1.382 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 4.150598e-02 | 1.382 |
| R-HSA-110312 | Translesion synthesis by REV1 | 4.150598e-02 | 1.382 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling | 4.150598e-02 | 1.382 |
| R-HSA-162588 | Budding and maturation of HIV virion | 4.197620e-02 | 1.377 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 4.265602e-02 | 1.370 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 4.283055e-02 | 1.368 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 4.307716e-02 | 1.366 |
| R-HSA-3371568 | Attenuation phase | 4.307716e-02 | 1.366 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 4.341246e-02 | 1.362 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 4.464536e-02 | 1.350 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 4.464536e-02 | 1.350 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 4.464536e-02 | 1.350 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 4.464536e-02 | 1.350 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 4.464536e-02 | 1.350 |
| R-HSA-381070 | IRE1alpha activates chaperones | 4.551841e-02 | 1.342 |
| R-HSA-1839120 | Signaling by FGFR1 amplification mutants | 4.575265e-02 | 1.340 |
| R-HSA-2023837 | Signaling by FGFR2 amplification mutants | 4.575265e-02 | 1.340 |
| R-HSA-8875513 | MET interacts with TNS proteins | 4.575265e-02 | 1.340 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 4.721849e-02 | 1.326 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 4.721849e-02 | 1.326 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 4.746939e-02 | 1.324 |
| R-HSA-5656121 | Translesion synthesis by POLI | 4.840957e-02 | 1.315 |
| R-HSA-169893 | Prolonged ERK activation events | 4.840957e-02 | 1.315 |
| R-HSA-9708530 | Regulation of BACH1 activity | 4.840957e-02 | 1.315 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 4.902932e-02 | 1.310 |
| R-HSA-9613354 | Lipophagy | 4.902932e-02 | 1.310 |
| R-HSA-2025928 | Calcineurin activates NFAT | 4.902932e-02 | 1.310 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 4.902932e-02 | 1.310 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 4.902932e-02 | 1.310 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 4.902932e-02 | 1.310 |
| R-HSA-912526 | Interleukin receptor SHC signaling | 4.905981e-02 | 1.309 |
| R-HSA-982772 | Growth hormone receptor signaling | 4.905981e-02 | 1.309 |
| R-HSA-3371571 | HSF1-dependent transactivation | 5.021429e-02 | 1.299 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 5.120031e-02 | 1.291 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 5.162164e-02 | 1.287 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 5.162164e-02 | 1.287 |
| R-HSA-397795 | G-protein beta:gamma signalling | 5.162164e-02 | 1.287 |
| R-HSA-186797 | Signaling by PDGF | 5.170756e-02 | 1.286 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 5.301499e-02 | 1.276 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 5.301499e-02 | 1.276 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 5.429822e-02 | 1.265 |
| R-HSA-429947 | Deadenylation of mRNA | 5.511961e-02 | 1.259 |
| R-HSA-6783589 | Interleukin-6 family signaling | 5.511961e-02 | 1.259 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 5.590722e-02 | 1.253 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 5.590722e-02 | 1.253 |
| R-HSA-5655862 | Translesion synthesis by POLK | 5.590722e-02 | 1.253 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 5.590722e-02 | 1.253 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 5.590722e-02 | 1.253 |
| R-HSA-72172 | mRNA Splicing | 5.638041e-02 | 1.249 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 5.691095e-02 | 1.245 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 5.691095e-02 | 1.245 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 5.936678e-02 | 1.226 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 5.939558e-02 | 1.226 |
| R-HSA-5140745 | WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 5.939558e-02 | 1.226 |
| R-HSA-74749 | Signal attenuation | 5.939558e-02 | 1.226 |
| R-HSA-140342 | Apoptosis induced DNA fragmentation | 5.939558e-02 | 1.226 |
| R-HSA-198203 | PI3K/AKT activation | 5.939558e-02 | 1.226 |
| R-HSA-2586552 | Signaling by Leptin | 5.939558e-02 | 1.226 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 5.939558e-02 | 1.226 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 5.946448e-02 | 1.226 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 6.040204e-02 | 1.219 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 6.094591e-02 | 1.215 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 6.159216e-02 | 1.210 |
| R-HSA-9830364 | Formation of the nephric duct | 6.159216e-02 | 1.210 |
| R-HSA-180746 | Nuclear import of Rev protein | 6.251375e-02 | 1.204 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 6.251375e-02 | 1.204 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 6.251375e-02 | 1.204 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 6.307382e-02 | 1.200 |
| R-HSA-1980143 | Signaling by NOTCH1 | 6.318999e-02 | 1.199 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 6.399206e-02 | 1.194 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 6.399206e-02 | 1.194 |
| R-HSA-4641263 | Regulation of FZD by ubiquitination | 6.399206e-02 | 1.194 |
| R-HSA-3229121 | Glycogen storage diseases | 6.399206e-02 | 1.194 |
| R-HSA-9702506 | Drug resistance of FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9700649 | Drug resistance of ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669937 | Drug resistance of KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669921 | KIT mutants bind TKIs | 6.539309e-02 | 1.184 |
| R-HSA-9702509 | FLT3 mutants bind TKIs | 6.539309e-02 | 1.184 |
| R-HSA-9703009 | tamatinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669914 | Dasatinib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669917 | Imatinib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669926 | Nilotinib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669936 | Sorafenib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9717323 | ceritinib-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702624 | sorafenib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702620 | quizartinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702614 | ponatinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9717264 | ASP-3026-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-5467343 | Deletions in the AMER1 gene destabilize the destruction complex | 6.539309e-02 | 1.184 |
| R-HSA-9717316 | alectinib-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702581 | crenolanib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702632 | sunitinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9661070 | Defective translocation of RB1 mutants to the nucleus | 6.539309e-02 | 1.184 |
| R-HSA-9717319 | brigatinib-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702590 | gilteritinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702636 | tandutinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702998 | linifanib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9723907 | Loss of Function of TP53 in Cancer | 6.539309e-02 | 1.184 |
| R-HSA-9717301 | NVP-TAE684-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669924 | Masitinib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702596 | lestaurtinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702577 | semaxanib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9669934 | Sunitinib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702605 | pexidartinib-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9717326 | crizotinib-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702569 | KW2449-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9723905 | Loss of function of TP53 in cancer due to loss of tetramerization ability | 6.539309e-02 | 1.184 |
| R-HSA-9669929 | Regorafenib-resistant KIT mutants | 6.539309e-02 | 1.184 |
| R-HSA-9702600 | midostaurin-resistant FLT3 mutants | 6.539309e-02 | 1.184 |
| R-HSA-9717329 | lorlatinib-resistant ALK mutants | 6.539309e-02 | 1.184 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 6.843050e-02 | 1.165 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 6.843050e-02 | 1.165 |
| R-HSA-5689901 | Metalloprotease DUBs | 6.847585e-02 | 1.164 |
| R-HSA-525793 | Myogenesis | 6.847585e-02 | 1.164 |
| R-HSA-9637687 | Suppression of phagosomal maturation | 6.847585e-02 | 1.164 |
| R-HSA-2122948 | Activated NOTCH1 Transmits Signal to the Nucleus | 6.847585e-02 | 1.164 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 6.957263e-02 | 1.158 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 7.069752e-02 | 1.151 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 7.069752e-02 | 1.151 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 7.069752e-02 | 1.151 |
| R-HSA-4839744 | Signaling by APC mutants | 7.069752e-02 | 1.151 |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 7.069752e-02 | 1.151 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 7.165276e-02 | 1.145 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 7.165276e-02 | 1.145 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 7.265362e-02 | 1.139 |
| R-HSA-75893 | TNF signaling | 7.271278e-02 | 1.138 |
| R-HSA-193648 | NRAGE signals death through JNK | 7.271278e-02 | 1.138 |
| R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 1.265136e-01 | 0.898 |
| R-HSA-9734091 | Drug-mediated inhibition of MET activation | 1.265136e-01 | 0.898 |
| R-HSA-9699150 | Defective DNA double strand break response due to BARD1 loss of function | 1.265136e-01 | 0.898 |
| R-HSA-5545483 | Defective Mismatch Repair Associated With MLH1 | 1.265136e-01 | 0.898 |
| R-HSA-5632987 | Defective Mismatch Repair Associated With PMS2 | 1.265136e-01 | 0.898 |
| R-HSA-3656248 | Defective HEXB causes GM2G2 (Hyaluronan metabolism) | 1.265136e-01 | 0.898 |
| R-HSA-9663199 | Defective DNA double strand break response due to BRCA1 loss of function | 1.265136e-01 | 0.898 |
| R-HSA-5602566 | TICAM1 deficiency - HSE | 1.265136e-01 | 0.898 |
| R-HSA-74713 | IRS activation | 8.221062e-02 | 1.085 |
| R-HSA-165158 | Activation of AKT2 | 8.221062e-02 | 1.085 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 8.221062e-02 | 1.085 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 1.247197e-01 | 0.904 |
| R-HSA-8951671 | RUNX3 regulates YAP1-mediated transcription | 1.247197e-01 | 0.904 |
| R-HSA-9912481 | Branched-chain ketoacid dehydrogenase kinase deficiency | 1.247197e-01 | 0.904 |
| R-HSA-1250342 | PI3K events in ERBB4 signaling | 8.288474e-02 | 1.082 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 1.475655e-01 | 0.831 |
| R-HSA-163767 | PP2A-mediated dephosphorylation of key metabolic factors | 1.475655e-01 | 0.831 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 1.475655e-01 | 0.831 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 1.475655e-01 | 0.831 |
| R-HSA-112412 | SOS-mediated signalling | 1.475655e-01 | 0.831 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 9.590190e-02 | 1.018 |
| R-HSA-2428933 | SHC-related events triggered by IGF1R | 9.590190e-02 | 1.018 |
| R-HSA-2033514 | FGFR3 mutant receptor activation | 1.096900e-01 | 0.960 |
| R-HSA-1839130 | Signaling by activated point mutants of FGFR3 | 1.096900e-01 | 0.960 |
| R-HSA-9796292 | Formation of axial mesoderm | 1.096900e-01 | 0.960 |
| R-HSA-9861559 | PDH complex synthesizes acetyl-CoA from PYR | 1.096900e-01 | 0.960 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 1.241875e-01 | 0.906 |
| R-HSA-5654221 | Phospholipase C-mediated cascade; FGFR2 | 9.164894e-02 | 1.038 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 1.019467e-01 | 0.992 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 1.127498e-01 | 0.948 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 9.155176e-02 | 1.038 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 9.155176e-02 | 1.038 |
| R-HSA-8853659 | RET signaling | 7.466068e-02 | 1.127 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 1.000298e-01 | 1.000 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 1.088861e-01 | 0.963 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 1.088861e-01 | 0.963 |
| R-HSA-8875878 | MET promotes cell motility | 8.805407e-02 | 1.055 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 1.181097e-01 | 0.928 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 9.521124e-02 | 1.021 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 7.729492e-02 | 1.112 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 1.276886e-01 | 0.894 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 1.026698e-01 | 0.989 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 1.026698e-01 | 0.989 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 1.163759e-01 | 0.934 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 1.032341e-01 | 0.986 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 1.471792e-01 | 0.832 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 8.626042e-02 | 1.064 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 1.333513e-01 | 0.875 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 1.184691e-01 | 0.926 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 1.023682e-01 | 0.990 |
| R-HSA-5696398 | Nucleotide Excision Repair | 1.049164e-01 | 0.979 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 7.466068e-02 | 1.127 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 9.942136e-02 | 1.003 |
| R-HSA-418885 | DCC mediated attractive signaling | 1.393315e-01 | 0.856 |
| R-HSA-167590 | Nef Mediated CD4 Down-regulation | 1.475655e-01 | 0.831 |
| R-HSA-190241 | FGFR2 ligand binding and activation | 1.019467e-01 | 0.992 |
| R-HSA-73893 | DNA Damage Bypass | 9.572784e-02 | 1.019 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 1.000298e-01 | 1.000 |
| R-HSA-113510 | E2F mediated regulation of DNA replication | 8.187815e-02 | 1.087 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 1.104245e-01 | 0.957 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 1.096900e-01 | 0.960 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 7.576734e-02 | 1.121 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 8.465134e-02 | 1.072 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 8.805407e-02 | 1.055 |
| R-HSA-113501 | Inhibition of replication initiation of damaged DNA by RB1/E2F1 | 8.288474e-02 | 1.082 |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation | 9.590190e-02 | 1.018 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 9.155176e-02 | 1.038 |
| R-HSA-9007101 | Rab regulation of trafficking | 1.133300e-01 | 0.946 |
| R-HSA-5693538 | Homology Directed Repair | 1.180658e-01 | 0.928 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 9.765061e-02 | 1.010 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 7.466068e-02 | 1.127 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 1.405192e-01 | 0.852 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 8.288474e-02 | 1.082 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 1.475655e-01 | 0.831 |
| R-HSA-72764 | Eukaryotic Translation Termination | 1.101984e-01 | 0.958 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 7.513774e-02 | 1.124 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 1.240346e-01 | 0.906 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 1.247197e-01 | 0.904 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 1.247197e-01 | 0.904 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 1.000298e-01 | 1.000 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 1.276886e-01 | 0.894 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 1.237355e-01 | 0.908 |
| R-HSA-6784531 | tRNA processing in the nucleus | 1.066348e-01 | 0.972 |
| R-HSA-4791275 | Signaling by WNT in cancer | 1.181097e-01 | 0.928 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 8.187815e-02 | 1.087 |
| R-HSA-114608 | Platelet degranulation | 1.073800e-01 | 0.969 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 1.321096e-01 | 0.879 |
| R-HSA-169131 | Inhibition of PKR | 1.265136e-01 | 0.898 |
| R-HSA-8939245 | RUNX1 regulates transcription of genes involved in BCR signaling | 8.221062e-02 | 1.085 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 1.028520e-01 | 0.988 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 8.288474e-02 | 1.082 |
| R-HSA-4839735 | Signaling by AXIN mutants | 8.288474e-02 | 1.082 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 8.652204e-02 | 1.063 |
| R-HSA-9711097 | Cellular response to starvation | 9.489460e-02 | 1.023 |
| R-HSA-9707616 | Heme signaling | 1.066348e-01 | 0.972 |
| R-HSA-73894 | DNA Repair | 1.250847e-01 | 0.903 |
| R-HSA-418346 | Platelet homeostasis | 1.096898e-01 | 0.960 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 1.066348e-01 | 0.972 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 1.475655e-01 | 0.831 |
| R-HSA-447041 | CHL1 interactions | 1.475655e-01 | 0.831 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 1.376095e-01 | 0.861 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 1.475655e-01 | 0.831 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 1.127498e-01 | 0.948 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 1.416376e-01 | 0.849 |
| R-HSA-2559583 | Cellular Senescence | 1.350825e-01 | 0.869 |
| R-HSA-162587 | HIV Life Cycle | 1.426699e-01 | 0.846 |
| R-HSA-9854909 | Regulation of MITF-M dependent genes involved in invasion | 8.221062e-02 | 1.085 |
| R-HSA-8935964 | RUNX1 regulates expression of components of tight junctions | 1.028520e-01 | 0.988 |
| R-HSA-5578768 | Physiological factors | 1.241875e-01 | 0.906 |
| R-HSA-901032 | ER Quality Control Compartment (ERQC) | 7.576734e-02 | 1.121 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 9.155176e-02 | 1.038 |
| R-HSA-379724 | tRNA Aminoacylation | 9.449184e-02 | 1.025 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 1.247197e-01 | 0.904 |
| R-HSA-2408557 | Selenocysteine synthesis | 1.434673e-01 | 0.843 |
| R-HSA-8982491 | Glycogen metabolism | 1.026698e-01 | 0.989 |
| R-HSA-70171 | Glycolysis | 7.891996e-02 | 1.103 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 1.276886e-01 | 0.894 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 1.357760e-01 | 0.867 |
| R-HSA-70326 | Glucose metabolism | 1.133300e-01 | 0.946 |
| R-HSA-8964038 | LDL clearance | 1.240346e-01 | 0.906 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 1.354000e-01 | 0.868 |
| R-HSA-9636383 | Prevention of phagosomal-lysosomal fusion | 1.019467e-01 | 0.992 |
| R-HSA-2979096 | NOTCH2 Activation and Transmission of Signal to the Nucleus | 1.019467e-01 | 0.992 |
| R-HSA-2672351 | Stimuli-sensing channels | 1.196107e-01 | 0.922 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 1.462176e-01 | 0.835 |
| R-HSA-3322077 | Glycogen synthesis | 9.164894e-02 | 1.038 |
| R-HSA-351202 | Metabolism of polyamines | 9.449184e-02 | 1.025 |
| R-HSA-203615 | eNOS activation | 1.478584e-01 | 0.830 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 1.478584e-01 | 0.830 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 1.478584e-01 | 0.830 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 1.479473e-01 | 0.830 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 1.479473e-01 | 0.830 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 1.533985e-01 | 0.814 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 1.541404e-01 | 0.812 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 1.550586e-01 | 0.810 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 1.554299e-01 | 0.808 |
| R-HSA-192823 | Viral mRNA Translation | 1.556144e-01 | 0.808 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 1.584202e-01 | 0.800 |
| R-HSA-1266695 | Interleukin-7 signaling | 1.605207e-01 | 0.794 |
| R-HSA-9620244 | Long-term potentiation | 1.605207e-01 | 0.794 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 1.612456e-01 | 0.793 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 1.612456e-01 | 0.793 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 1.627754e-01 | 0.788 |
| R-HSA-6782135 | Dual incision in TC-NER | 1.638882e-01 | 0.785 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 1.692791e-01 | 0.771 |
| R-HSA-74158 | RNA Polymerase III Transcription | 1.692791e-01 | 0.771 |
| R-HSA-8875656 | MET receptor recycling | 1.711682e-01 | 0.767 |
| R-HSA-164940 | Nef mediated downregulation of MHC class I complex cell surface expression | 1.711682e-01 | 0.767 |
| R-HSA-9012546 | Interleukin-18 signaling | 1.711682e-01 | 0.767 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 1.713052e-01 | 0.766 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 1.713052e-01 | 0.766 |
| R-HSA-9837999 | Mitochondrial protein degradation | 1.722358e-01 | 0.764 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 1.723907e-01 | 0.763 |
| R-HSA-9033241 | Peroxisomal protein import | 1.725471e-01 | 0.763 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 1.725471e-01 | 0.763 |
| R-HSA-8874081 | MET activates PTK2 signaling | 1.734676e-01 | 0.761 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 1.734676e-01 | 0.761 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 1.734676e-01 | 0.761 |
| R-HSA-3295583 | TRP channels | 1.734676e-01 | 0.761 |
| R-HSA-2408522 | Selenoamino acid metabolism | 1.775413e-01 | 0.751 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 1.793049e-01 | 0.746 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 1.804189e-01 | 0.744 |
| R-HSA-112315 | Transmission across Chemical Synapses | 1.812740e-01 | 0.742 |
| R-HSA-70263 | Gluconeogenesis | 1.822340e-01 | 0.739 |
| R-HSA-1839128 | FGFR4 mutant receptor activation | 1.836404e-01 | 0.736 |
| R-HSA-164939 | Nef mediated downregulation of CD28 cell surface expression | 1.836404e-01 | 0.736 |
| R-HSA-2033515 | t(4;14) translocations of FGFR3 | 1.836404e-01 | 0.736 |
| R-HSA-9669935 | Signaling by juxtamembrane domain KIT mutants | 1.836404e-01 | 0.736 |
| R-HSA-8853333 | Signaling by FGFR2 fusions | 1.836404e-01 | 0.736 |
| R-HSA-9680187 | Signaling by extracellular domain mutants of KIT | 1.836404e-01 | 0.736 |
| R-HSA-8853334 | Signaling by FGFR3 fusions in cancer | 1.836404e-01 | 0.736 |
| R-HSA-5687583 | Defective SLC34A2 causes PALM | 1.836404e-01 | 0.736 |
| R-HSA-5602636 | IKBKB deficiency causes SCID | 1.836404e-01 | 0.736 |
| R-HSA-5619087 | Defective SLC12A3 causes Gitelman syndrome (GS) | 1.836404e-01 | 0.736 |
| R-HSA-9669933 | Signaling by kinase domain mutants of KIT | 1.836404e-01 | 0.736 |
| R-HSA-5619109 | Defective SLC6A2 causes orthostatic intolerance (OI) | 1.836404e-01 | 0.736 |
| R-HSA-5603027 | IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... | 1.836404e-01 | 0.736 |
| R-HSA-9916722 | 3-hydroxyisobutyryl-CoA hydrolase deficiency | 1.836404e-01 | 0.736 |
| R-HSA-4085023 | Defective GFPT1 causes CMSTA1 | 1.836404e-01 | 0.736 |
| R-HSA-9632700 | Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... | 1.836404e-01 | 0.736 |
| R-HSA-5619045 | Defective SLC34A2 causes pulmonary alveolar microlithiasis (PALM) | 1.836404e-01 | 0.736 |
| R-HSA-9630794 | Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... | 1.836404e-01 | 0.736 |
| R-HSA-5674404 | PTEN Loss of Function in Cancer | 1.836404e-01 | 0.736 |
| R-HSA-9915355 | Beta-ketothiolase deficiency | 1.836404e-01 | 0.736 |
| R-HSA-9630750 | Evasion of Oncogene Induced Senescence Due to p16INK4A Defects | 1.836404e-01 | 0.736 |
| R-HSA-9632693 | Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects | 1.836404e-01 | 0.736 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 1.836404e-01 | 0.736 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 1.867588e-01 | 0.729 |
| R-HSA-201451 | Signaling by BMP | 1.867588e-01 | 0.729 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 1.867588e-01 | 0.729 |
| R-HSA-264876 | Insulin processing | 1.867588e-01 | 0.729 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 1.880087e-01 | 0.726 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 1.881415e-01 | 0.726 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 1.911662e-01 | 0.719 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 1.918225e-01 | 0.717 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 1.953314e-01 | 0.709 |
| R-HSA-201688 | WNT mediated activation of DVL | 1.953314e-01 | 0.709 |
| R-HSA-9700645 | ALK mutants bind TKIs | 1.953314e-01 | 0.709 |
| R-HSA-176974 | Unwinding of DNA | 1.953314e-01 | 0.709 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 1.953314e-01 | 0.709 |
| R-HSA-2465910 | MASTL Facilitates Mitotic Progression | 1.953314e-01 | 0.709 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 1.953314e-01 | 0.709 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 2.003647e-01 | 0.698 |
| R-HSA-622312 | Inflammasomes | 2.003647e-01 | 0.698 |
| R-HSA-9748787 | Azathioprine ADME | 2.025599e-01 | 0.693 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 2.034727e-01 | 0.691 |
| R-HSA-210993 | Tie2 Signaling | 2.051077e-01 | 0.688 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 2.051077e-01 | 0.688 |
| R-HSA-2033519 | Activated point mutants of FGFR2 | 2.051077e-01 | 0.688 |
| R-HSA-8849932 | Synaptic adhesion-like molecules | 2.051077e-01 | 0.688 |
| R-HSA-8951664 | Neddylation | 2.076554e-01 | 0.683 |
| R-HSA-180024 | DARPP-32 events | 2.142554e-01 | 0.669 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 2.142554e-01 | 0.669 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 2.153517e-01 | 0.667 |
| R-HSA-5260271 | Diseases of Immune System | 2.153517e-01 | 0.667 |
| R-HSA-202433 | Generation of second messenger molecules | 2.153517e-01 | 0.667 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 2.153517e-01 | 0.667 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 2.198811e-01 | 0.658 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 2.198811e-01 | 0.658 |
| R-HSA-9020956 | Interleukin-27 signaling | 2.198811e-01 | 0.658 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 2.198811e-01 | 0.658 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 2.198811e-01 | 0.658 |
| R-HSA-9761174 | Formation of intermediate mesoderm | 2.198811e-01 | 0.658 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 2.225423e-01 | 0.653 |
| R-HSA-392517 | Rap1 signalling | 2.225423e-01 | 0.653 |
| R-HSA-844456 | The NLRP3 inflammasome | 2.225423e-01 | 0.653 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 2.284013e-01 | 0.641 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 2.284013e-01 | 0.641 |
| R-HSA-1221632 | Meiotic synapsis | 2.344724e-01 | 0.630 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 2.370343e-01 | 0.625 |
| R-HSA-211736 | Stimulation of the cell death response by PAK-2p34 | 2.370343e-01 | 0.625 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 2.370343e-01 | 0.625 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 2.370343e-01 | 0.625 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 2.370343e-01 | 0.625 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 2.370343e-01 | 0.625 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 2.370343e-01 | 0.625 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 2.370343e-01 | 0.625 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 2.370343e-01 | 0.625 |
| R-HSA-5683371 | Defective ABCB6 causes MCOPCB7 | 2.370343e-01 | 0.625 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 2.370343e-01 | 0.625 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 2.370343e-01 | 0.625 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 2.370343e-01 | 0.625 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 2.370343e-01 | 0.625 |
| R-HSA-844615 | The AIM2 inflammasome | 2.370343e-01 | 0.625 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 2.370343e-01 | 0.625 |
| R-HSA-9675132 | Diseases of cellular response to stress | 2.370343e-01 | 0.625 |
| R-HSA-9630747 | Diseases of Cellular Senescence | 2.370343e-01 | 0.625 |
| R-HSA-75108 | Activation, myristolyation of BID and translocation to mitochondria | 2.370343e-01 | 0.625 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 2.383175e-01 | 0.623 |
| R-HSA-9683701 | Translation of Structural Proteins | 2.397242e-01 | 0.620 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 2.402548e-01 | 0.619 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 2.402548e-01 | 0.619 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 2.446636e-01 | 0.611 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS | 2.446636e-01 | 0.611 |
| R-HSA-190377 | FGFR2b ligand binding and activation | 2.446636e-01 | 0.611 |
| R-HSA-983712 | Ion channel transport | 2.487585e-01 | 0.604 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 2.521814e-01 | 0.598 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 2.523652e-01 | 0.598 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 2.572558e-01 | 0.590 |
| R-HSA-167044 | Signalling to RAS | 2.581896e-01 | 0.588 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 2.581896e-01 | 0.588 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 2.627187e-01 | 0.581 |
| R-HSA-9833110 | RSV-host interactions | 2.638005e-01 | 0.579 |
| R-HSA-72312 | rRNA processing | 2.658389e-01 | 0.575 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 2.660028e-01 | 0.575 |
| R-HSA-1234158 | Regulation of gene expression by Hypoxia-inducible Factor | 2.695435e-01 | 0.569 |
| R-HSA-9026519 | Activated NTRK2 signals through RAS | 2.695435e-01 | 0.569 |
| R-HSA-1839122 | Signaling by activated point mutants of FGFR1 | 2.695435e-01 | 0.569 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 2.695435e-01 | 0.569 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 2.695435e-01 | 0.569 |
| R-HSA-202670 | ERKs are inactivated | 2.695435e-01 | 0.569 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 2.695435e-01 | 0.569 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 2.720747e-01 | 0.565 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 2.720747e-01 | 0.565 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 2.762936e-01 | 0.559 |
| R-HSA-9617828 | FOXO-mediated transcription of cell cycle genes | 2.762936e-01 | 0.559 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 2.762936e-01 | 0.559 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 2.791676e-01 | 0.554 |
| R-HSA-1989781 | PPARA activates gene expression | 2.864539e-01 | 0.543 |
| R-HSA-3249367 | STAT6-mediated induction of chemokines | 2.869390e-01 | 0.542 |
| R-HSA-844455 | The NLRP1 inflammasome | 2.869390e-01 | 0.542 |
| R-HSA-209563 | Axonal growth stimulation | 2.869390e-01 | 0.542 |
| R-HSA-8853336 | Signaling by plasma membrane FGFR1 fusions | 2.869390e-01 | 0.542 |
| R-HSA-5368598 | Negative regulation of TCF-dependent signaling by DVL-interacting proteins | 2.869390e-01 | 0.542 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 2.869390e-01 | 0.542 |
| R-HSA-8865999 | MET activates PTPN11 | 2.869390e-01 | 0.542 |
| R-HSA-5660862 | Defective SLC7A7 causes lysinuric protein intolerance (LPI) | 2.869390e-01 | 0.542 |
| R-HSA-9636249 | Inhibition of nitric oxide production | 2.869390e-01 | 0.542 |
| R-HSA-8875791 | MET activates STAT3 | 2.869390e-01 | 0.542 |
| R-HSA-427589 | Type II Na+/Pi cotransporters | 2.869390e-01 | 0.542 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 2.869390e-01 | 0.542 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 2.869484e-01 | 0.542 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 2.869484e-01 | 0.542 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 2.904192e-01 | 0.537 |
| R-HSA-8851805 | MET activates RAS signaling | 2.944023e-01 | 0.531 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 2.944023e-01 | 0.531 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 2.944023e-01 | 0.531 |
| R-HSA-8983432 | Interleukin-15 signaling | 2.944023e-01 | 0.531 |
| R-HSA-8984722 | Interleukin-35 Signalling | 2.944023e-01 | 0.531 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 2.944023e-01 | 0.531 |
| R-HSA-4641265 | Repression of WNT target genes | 2.944023e-01 | 0.531 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 2.944023e-01 | 0.531 |
| R-HSA-8983711 | OAS antiviral response | 2.944023e-01 | 0.531 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 2.945163e-01 | 0.531 |
| R-HSA-350054 | Notch-HLH transcription pathway | 2.945163e-01 | 0.531 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 2.945163e-01 | 0.531 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 2.996824e-01 | 0.523 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 3.004808e-01 | 0.522 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 3.019334e-01 | 0.520 |
| R-HSA-1980145 | Signaling by NOTCH2 | 3.019334e-01 | 0.520 |
| R-HSA-194441 | Metabolism of non-coding RNA | 3.022094e-01 | 0.520 |
| R-HSA-191859 | snRNP Assembly | 3.022094e-01 | 0.520 |
| R-HSA-186712 | Regulation of beta-cell development | 3.022094e-01 | 0.520 |
| R-HSA-9658195 | Leishmania infection | 3.059729e-01 | 0.514 |
| R-HSA-9824443 | Parasitic Infection Pathways | 3.059729e-01 | 0.514 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 3.108623e-01 | 0.507 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 3.128099e-01 | 0.505 |
| R-HSA-8854691 | Interleukin-20 family signaling | 3.128099e-01 | 0.505 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 3.170030e-01 | 0.499 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 3.191365e-01 | 0.496 |
| R-HSA-190375 | FGFR2c ligand binding and activation | 3.191365e-01 | 0.496 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 3.191365e-01 | 0.496 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 3.191365e-01 | 0.496 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 3.191365e-01 | 0.496 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 3.191365e-01 | 0.496 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 3.191365e-01 | 0.496 |
| R-HSA-8877330 | RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) | 3.191365e-01 | 0.496 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 3.191365e-01 | 0.496 |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome | 3.191365e-01 | 0.496 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 3.254637e-01 | 0.487 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 3.311295e-01 | 0.480 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 3.316517e-01 | 0.479 |
| R-HSA-71403 | Citric acid cycle (TCA cycle) | 3.316517e-01 | 0.479 |
| R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death | 3.335822e-01 | 0.477 |
| R-HSA-165181 | Inhibition of TSC complex formation by PKB | 3.335822e-01 | 0.477 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 3.335822e-01 | 0.477 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 3.335822e-01 | 0.477 |
| R-HSA-1307965 | betaKlotho-mediated ligand binding | 3.335822e-01 | 0.477 |
| R-HSA-2978092 | Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate | 3.335822e-01 | 0.477 |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... | 3.335822e-01 | 0.477 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 3.335822e-01 | 0.477 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 3.335822e-01 | 0.477 |
| R-HSA-191650 | Regulation of gap junction activity | 3.335822e-01 | 0.477 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 3.335822e-01 | 0.477 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 3.335822e-01 | 0.477 |
| R-HSA-5626978 | TNFR1-mediated ceramide production | 3.335822e-01 | 0.477 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 | 3.335822e-01 | 0.477 |
| R-HSA-69560 | Transcriptional activation of p53 responsive genes | 3.335822e-01 | 0.477 |
| R-HSA-9705677 | SARS-CoV-2 targets PDZ proteins in cell-cell junction | 3.335822e-01 | 0.477 |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity | 3.335822e-01 | 0.477 |
| R-HSA-111448 | Activation of NOXA and translocation to mitochondria | 3.335822e-01 | 0.477 |
| R-HSA-193670 | p75NTR negatively regulates cell cycle via SC1 | 3.335822e-01 | 0.477 |
| R-HSA-205025 | NADE modulates death signalling | 3.335822e-01 | 0.477 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 3.373592e-01 | 0.472 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 3.436560e-01 | 0.464 |
| R-HSA-1170546 | Prolactin receptor signaling | 3.436560e-01 | 0.464 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 3.436560e-01 | 0.464 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 3.436560e-01 | 0.464 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 3.436560e-01 | 0.464 |
| R-HSA-5654227 | Phospholipase C-mediated cascade; FGFR3 | 3.436560e-01 | 0.464 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 3.436560e-01 | 0.464 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 3.436560e-01 | 0.464 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 3.436560e-01 | 0.464 |
| R-HSA-391160 | Signal regulatory protein family interactions | 3.436560e-01 | 0.464 |
| R-HSA-1482798 | Acyl chain remodeling of CL | 3.436560e-01 | 0.464 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 3.436560e-01 | 0.464 |
| R-HSA-9679514 | SARS-CoV-1 Genome Replication and Transcription | 3.436560e-01 | 0.464 |
| R-HSA-3000157 | Laminin interactions | 3.494328e-01 | 0.457 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 3.494328e-01 | 0.457 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 3.494328e-01 | 0.457 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 3.494328e-01 | 0.457 |
| R-HSA-3214842 | HDMs demethylate histones | 3.494328e-01 | 0.457 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 3.532352e-01 | 0.452 |
| R-HSA-936837 | Ion transport by P-type ATPases | 3.610418e-01 | 0.442 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 3.624640e-01 | 0.441 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 3.624640e-01 | 0.441 |
| R-HSA-9734767 | Developmental Cell Lineages | 3.641845e-01 | 0.439 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 3.676805e-01 | 0.435 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 3.676805e-01 | 0.435 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 3.678833e-01 | 0.434 |
| R-HSA-73780 | RNA Polymerase III Chain Elongation | 3.678833e-01 | 0.434 |
| R-HSA-190239 | FGFR3 ligand binding and activation | 3.678833e-01 | 0.434 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 3.678833e-01 | 0.434 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 3.678833e-01 | 0.434 |
| R-HSA-196780 | Biotin transport and metabolism | 3.678833e-01 | 0.434 |
| R-HSA-171007 | p38MAPK events | 3.678833e-01 | 0.434 |
| R-HSA-9609507 | Protein localization | 3.740659e-01 | 0.427 |
| R-HSA-909733 | Interferon alpha/beta signaling | 3.761197e-01 | 0.425 |
| R-HSA-9818026 | NFE2L2 regulating inflammation associated genes | 3.771770e-01 | 0.423 |
| R-HSA-190374 | FGFR1c and Klotho ligand binding and activation | 3.771770e-01 | 0.423 |
| R-HSA-203754 | NOSIP mediated eNOS trafficking | 3.771770e-01 | 0.423 |
| R-HSA-9032759 | NTRK2 activates RAC1 | 3.771770e-01 | 0.423 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 3.771770e-01 | 0.423 |
| R-HSA-9931529 | Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK | 3.771770e-01 | 0.423 |
| R-HSA-8849474 | PTK6 Activates STAT3 | 3.771770e-01 | 0.423 |
| R-HSA-71737 | Pyrophosphate hydrolysis | 3.771770e-01 | 0.423 |
| R-HSA-9026403 | Biosynthesis of DPAn-3-derived 13-series resolvins | 3.771770e-01 | 0.423 |
| R-HSA-8866376 | Reelin signalling pathway | 3.771770e-01 | 0.423 |
| R-HSA-447038 | NrCAM interactions | 3.771770e-01 | 0.423 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 3.776216e-01 | 0.423 |
| R-HSA-9648002 | RAS processing | 3.776216e-01 | 0.423 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 3.858360e-01 | 0.414 |
| R-HSA-193807 | Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 3.858360e-01 | 0.414 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 3.858360e-01 | 0.414 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 3.917517e-01 | 0.407 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 3.917517e-01 | 0.407 |
| R-HSA-399955 | SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 3.917517e-01 | 0.407 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 3.917517e-01 | 0.407 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 3.917517e-01 | 0.407 |
| R-HSA-9634600 | Regulation of glycolysis by fructose 2,6-bisphosphate metabolism | 3.917517e-01 | 0.407 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 3.917517e-01 | 0.407 |
| R-HSA-9854311 | Maturation of TCA enzymes and regulation of TCA cycle | 3.927436e-01 | 0.406 |
| R-HSA-977225 | Amyloid fiber formation | 3.967275e-01 | 0.402 |
| R-HSA-73614 | Pyrimidine salvage | 4.038655e-01 | 0.394 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 4.088613e-01 | 0.388 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 4.152046e-01 | 0.382 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 4.152046e-01 | 0.382 |
| R-HSA-2892247 | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | 4.152046e-01 | 0.382 |
| R-HSA-182218 | Nef Mediated CD8 Down-regulation | 4.179225e-01 | 0.379 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 4.179225e-01 | 0.379 |
| R-HSA-5638302 | Signaling by Overexpressed Wild-Type EGFR in Cancer | 4.179225e-01 | 0.379 |
| R-HSA-8985586 | SLIT2:ROBO1 increases RHOA activity | 4.179225e-01 | 0.379 |
| R-HSA-5638303 | Inhibition of Signaling by Overexpressed EGFR | 4.179225e-01 | 0.379 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 4.179225e-01 | 0.379 |
| R-HSA-9907570 | Loss-of-function mutations in DLD cause MSUD3/DLDD | 4.179225e-01 | 0.379 |
| R-HSA-9865113 | Loss-of-function mutations in DBT cause MSUD2 | 4.179225e-01 | 0.379 |
| R-HSA-5576894 | Phase 1 - inactivation of fast Na+ channels | 4.179225e-01 | 0.379 |
| R-HSA-5659898 | Intestinal saccharidase deficiencies | 4.179225e-01 | 0.379 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 4.179225e-01 | 0.379 |
| R-HSA-5660668 | CLEC7A/inflammasome pathway | 4.179225e-01 | 0.379 |
| R-HSA-68689 | CDC6 association with the ORC:origin complex | 4.179225e-01 | 0.379 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 4.179225e-01 | 0.379 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 4.179225e-01 | 0.379 |
| R-HSA-165160 | PDE3B signalling | 4.179225e-01 | 0.379 |
| R-HSA-109703 | PKB-mediated events | 4.179225e-01 | 0.379 |
| R-HSA-195399 | VEGF binds to VEGFR leading to receptor dimerization | 4.179225e-01 | 0.379 |
| R-HSA-194313 | VEGF ligand-receptor interactions | 4.179225e-01 | 0.379 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 4.179225e-01 | 0.379 |
| R-HSA-9758919 | Epithelial-Mesenchymal Transition (EMT) during gastrulation | 4.179225e-01 | 0.379 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 4.179225e-01 | 0.379 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 4.179225e-01 | 0.379 |
| R-HSA-9860276 | SLC15A4:TASL-dependent IRF5 activation | 4.179225e-01 | 0.379 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 4.204477e-01 | 0.376 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 4.217380e-01 | 0.375 |
| R-HSA-5578775 | Ion homeostasis | 4.351209e-01 | 0.361 |
| R-HSA-5654219 | Phospholipase C-mediated cascade: FGFR1 | 4.381942e-01 | 0.358 |
| R-HSA-139853 | Elevation of cytosolic Ca2+ levels | 4.381942e-01 | 0.358 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 4.381942e-01 | 0.358 |
| R-HSA-9827857 | Specification of primordial germ cells | 4.381942e-01 | 0.358 |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome | 4.381942e-01 | 0.358 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 4.394249e-01 | 0.357 |
| R-HSA-68962 | Activation of the pre-replicative complex | 4.394249e-01 | 0.357 |
| R-HSA-5621480 | Dectin-2 family | 4.481574e-01 | 0.349 |
| R-HSA-8854214 | TBC/RABGAPs | 4.524746e-01 | 0.344 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 4.558014e-01 | 0.341 |
| R-HSA-9645135 | STAT5 Activation | 4.560046e-01 | 0.341 |
| R-HSA-5263617 | Metabolism of ingested MeSeO2H into MeSeH | 4.560046e-01 | 0.341 |
| R-HSA-9912529 | H139Hfs13* PPM1K causes a mild variant of MSUD | 4.560046e-01 | 0.341 |
| R-HSA-113507 | E2F-enabled inhibition of pre-replication complex formation | 4.560046e-01 | 0.341 |
| R-HSA-6806942 | MET Receptor Activation | 4.560046e-01 | 0.341 |
| R-HSA-8939256 | RUNX1 regulates transcription of genes involved in WNT signaling | 4.560046e-01 | 0.341 |
| R-HSA-389542 | NADPH regeneration | 4.560046e-01 | 0.341 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 4.560046e-01 | 0.341 |
| R-HSA-69478 | G2/M DNA replication checkpoint | 4.560046e-01 | 0.341 |
| R-HSA-9842640 | Signaling by LTK in cancer | 4.560046e-01 | 0.341 |
| R-HSA-8964011 | HDL clearance | 4.560046e-01 | 0.341 |
| R-HSA-5694530 | Cargo concentration in the ER | 4.569003e-01 | 0.340 |
| R-HSA-112316 | Neuronal System | 4.587768e-01 | 0.338 |
| R-HSA-73980 | RNA Polymerase III Transcription Termination | 4.606808e-01 | 0.337 |
| R-HSA-190242 | FGFR1 ligand binding and activation | 4.606808e-01 | 0.337 |
| R-HSA-180292 | GAB1 signalosome | 4.606808e-01 | 0.337 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 4.606808e-01 | 0.337 |
| R-HSA-156711 | Polo-like kinase mediated events | 4.606808e-01 | 0.337 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 4.611153e-01 | 0.336 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 4.611153e-01 | 0.336 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 4.613439e-01 | 0.336 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 4.671274e-01 | 0.331 |
| R-HSA-69190 | DNA strand elongation | 4.741409e-01 | 0.324 |
| R-HSA-500753 | Pyrimidine biosynthesis | 4.826320e-01 | 0.316 |
| R-HSA-2142688 | Synthesis of 5-eicosatetraenoic acids | 4.826320e-01 | 0.316 |
| R-HSA-449836 | Other interleukin signaling | 4.826320e-01 | 0.316 |
| R-HSA-9694682 | SARS-CoV-2 Genome Replication and Transcription | 4.826320e-01 | 0.316 |
| R-HSA-156590 | Glutathione conjugation | 4.867497e-01 | 0.313 |
| R-HSA-917937 | Iron uptake and transport | 4.906212e-01 | 0.309 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 4.911254e-01 | 0.309 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 4.911254e-01 | 0.309 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 4.911254e-01 | 0.309 |
| R-HSA-8931987 | RUNX1 regulates estrogen receptor mediated transcription | 4.915974e-01 | 0.308 |
| R-HSA-203641 | NOSTRIN mediated eNOS trafficking | 4.915974e-01 | 0.308 |
| R-HSA-8849473 | PTK6 Expression | 4.915974e-01 | 0.308 |
| R-HSA-2562578 | TRIF-mediated programmed cell death | 4.915974e-01 | 0.308 |
| R-HSA-190371 | FGFR3b ligand binding and activation | 4.915974e-01 | 0.308 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 4.915974e-01 | 0.308 |
| R-HSA-1369007 | Mitochondrial ABC transporters | 4.915974e-01 | 0.308 |
| R-HSA-419771 | Opsins | 4.915974e-01 | 0.308 |
| R-HSA-114516 | Disinhibition of SNARE formation | 4.915974e-01 | 0.308 |
| R-HSA-1614603 | Cysteine formation from homocysteine | 4.915974e-01 | 0.308 |
| R-HSA-3371599 | Defective HLCS causes multiple carboxylase deficiency | 4.915974e-01 | 0.308 |
| R-HSA-9675135 | Diseases of DNA repair | 4.959858e-01 | 0.305 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 4.994047e-01 | 0.302 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 5.040214e-01 | 0.298 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 5.040214e-01 | 0.298 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 5.040214e-01 | 0.298 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 5.040214e-01 | 0.298 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 5.078351e-01 | 0.294 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 5.078351e-01 | 0.294 |
| R-HSA-189483 | Heme degradation | 5.078351e-01 | 0.294 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 5.078477e-01 | 0.294 |
| R-HSA-6811440 | Retrograde transport at the Trans-Golgi-Network | 5.101638e-01 | 0.292 |
| R-HSA-1268020 | Mitochondrial protein import | 5.119384e-01 | 0.291 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 5.241579e-01 | 0.281 |
| R-HSA-392499 | Metabolism of proteins | 5.242323e-01 | 0.280 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 5.242532e-01 | 0.280 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 5.242532e-01 | 0.280 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 5.242532e-01 | 0.280 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 5.248634e-01 | 0.280 |
| R-HSA-446107 | Type I hemidesmosome assembly | 5.248634e-01 | 0.280 |
| R-HSA-111995 | phospho-PLA2 pathway | 5.248634e-01 | 0.280 |
| R-HSA-212718 | EGFR interacts with phospholipase C-gamma | 5.248634e-01 | 0.280 |
| R-HSA-190370 | FGFR1b ligand binding and activation | 5.248634e-01 | 0.280 |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K | 5.248634e-01 | 0.280 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 5.248634e-01 | 0.280 |
| R-HSA-9020933 | Interleukin-23 signaling | 5.248634e-01 | 0.280 |
| R-HSA-8985947 | Interleukin-9 signaling | 5.248634e-01 | 0.280 |
| R-HSA-9927354 | Co-stimulation by ICOS | 5.248634e-01 | 0.280 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 5.248634e-01 | 0.280 |
| R-HSA-390696 | Adrenoceptors | 5.248634e-01 | 0.280 |
| R-HSA-193634 | Axonal growth inhibition (RHOA activation) | 5.248634e-01 | 0.280 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 5.248634e-01 | 0.280 |
| R-HSA-1592230 | Mitochondrial biogenesis | 5.261200e-01 | 0.279 |
| R-HSA-5576891 | Cardiac conduction | 5.352347e-01 | 0.271 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 5.358328e-01 | 0.271 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 5.450384e-01 | 0.264 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 5.450384e-01 | 0.264 |
| R-HSA-189085 | Digestion of dietary carbohydrate | 5.450384e-01 | 0.264 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 5.450384e-01 | 0.264 |
| R-HSA-68875 | Mitotic Prophase | 5.530735e-01 | 0.257 |
| R-HSA-211000 | Gene Silencing by RNA | 5.542071e-01 | 0.256 |
| R-HSA-428543 | Inactivation of CDC42 and RAC1 | 5.559545e-01 | 0.255 |
| R-HSA-9020958 | Interleukin-21 signaling | 5.559545e-01 | 0.255 |
| R-HSA-193697 | p75NTR regulates axonogenesis | 5.559545e-01 | 0.255 |
| R-HSA-379398 | Enzymatic degradation of Dopamine by monoamine oxidase | 5.559545e-01 | 0.255 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 5.559545e-01 | 0.255 |
| R-HSA-170984 | ARMS-mediated activation | 5.559545e-01 | 0.255 |
| R-HSA-8866907 | Activation of the TFAP2 (AP-2) family of transcription factors | 5.559545e-01 | 0.255 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 5.559545e-01 | 0.255 |
| R-HSA-8853383 | Lysosomal oligosaccharide catabolism | 5.559545e-01 | 0.255 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 5.559545e-01 | 0.255 |
| R-HSA-3323169 | Defects in biotin (Btn) metabolism | 5.559545e-01 | 0.255 |
| R-HSA-442380 | Zinc influx into cells by the SLC39 gene family | 5.559545e-01 | 0.255 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 5.646398e-01 | 0.248 |
| R-HSA-6803529 | FGFR2 alternative splicing | 5.646398e-01 | 0.248 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 5.646398e-01 | 0.248 |
| R-HSA-76071 | RNA Polymerase III Transcription Initiation From Type 3 Promoter | 5.646398e-01 | 0.248 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 5.649301e-01 | 0.248 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 5.716214e-01 | 0.243 |
| R-HSA-9830369 | Kidney development | 5.724871e-01 | 0.242 |
| R-HSA-72187 | mRNA 3'-end processing | 5.780869e-01 | 0.238 |
| R-HSA-9018682 | Biosynthesis of maresins | 5.836258e-01 | 0.234 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 5.836258e-01 | 0.234 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 5.841211e-01 | 0.233 |
| R-HSA-9858328 | OADH complex synthesizes glutaryl-CoA from 2-OA | 5.850130e-01 | 0.233 |
| R-HSA-9762292 | Regulation of CDH11 function | 5.850130e-01 | 0.233 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 5.850130e-01 | 0.233 |
| R-HSA-379397 | Enzymatic degradation of dopamine by COMT | 5.850130e-01 | 0.233 |
| R-HSA-9948001 | CASP4 inflammasome assembly | 5.850130e-01 | 0.233 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 5.850130e-01 | 0.233 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 5.867456e-01 | 0.232 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 5.910139e-01 | 0.228 |
| R-HSA-1500620 | Meiosis | 6.001738e-01 | 0.222 |
| R-HSA-1483249 | Inositol phosphate metabolism | 6.001793e-01 | 0.222 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 6.015233e-01 | 0.221 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 6.019931e-01 | 0.220 |
| R-HSA-9865881 | Complex III assembly | 6.019931e-01 | 0.220 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 6.019931e-01 | 0.220 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 6.019931e-01 | 0.220 |
| R-HSA-8863678 | Neurodegenerative Diseases | 6.019931e-01 | 0.220 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 6.121714e-01 | 0.213 |
| R-HSA-192814 | vRNA Synthesis | 6.121714e-01 | 0.213 |
| R-HSA-192905 | vRNP Assembly | 6.121714e-01 | 0.213 |
| R-HSA-9706019 | RHOBTB3 ATPase cycle | 6.121714e-01 | 0.213 |
| R-HSA-77108 | Utilization of Ketone Bodies | 6.121714e-01 | 0.213 |
| R-HSA-425381 | Bicarbonate transporters | 6.121714e-01 | 0.213 |
| R-HSA-9026290 | Biosynthesis of DPAn-3-derived maresins | 6.121714e-01 | 0.213 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 6.121714e-01 | 0.213 |
| R-HSA-9758890 | Transport of RCbl within the body | 6.121714e-01 | 0.213 |
| R-HSA-391908 | Prostanoid ligand receptors | 6.121714e-01 | 0.213 |
| R-HSA-75205 | Dissolution of Fibrin Clot | 6.121714e-01 | 0.213 |
| R-HSA-3214815 | HDACs deacetylate histones | 6.161532e-01 | 0.210 |
| R-HSA-418597 | G alpha (z) signalling events | 6.161532e-01 | 0.210 |
| R-HSA-9753281 | Paracetamol ADME | 6.161532e-01 | 0.210 |
| R-HSA-3000178 | ECM proteoglycans | 6.179634e-01 | 0.209 |
| R-HSA-8978934 | Metabolism of cofactors | 6.179634e-01 | 0.209 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 6.197413e-01 | 0.208 |
| R-HSA-70221 | Glycogen breakdown (glycogenolysis) | 6.197413e-01 | 0.208 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 6.197413e-01 | 0.208 |
| R-HSA-420029 | Tight junction interactions | 6.197413e-01 | 0.208 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 6.283551e-01 | 0.202 |
| R-HSA-499943 | Interconversion of nucleotide di- and triphosphates | 6.288754e-01 | 0.201 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 6.300162e-01 | 0.201 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 6.368728e-01 | 0.196 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 6.368728e-01 | 0.196 |
| R-HSA-9638630 | Attachment of bacteria to epithelial cells | 6.368728e-01 | 0.196 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 6.375541e-01 | 0.195 |
| R-HSA-5358493 | Synthesis of diphthamide-EEF2 | 6.375541e-01 | 0.195 |
| R-HSA-425561 | Sodium/Calcium exchangers | 6.375541e-01 | 0.195 |
| R-HSA-4086398 | Ca2+ pathway | 6.395965e-01 | 0.194 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 6.395965e-01 | 0.194 |
| R-HSA-1483255 | PI Metabolism | 6.417297e-01 | 0.193 |
| R-HSA-4839726 | Chromatin organization | 6.433105e-01 | 0.192 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 6.437234e-01 | 0.191 |
| R-HSA-3247509 | Chromatin modifying enzymes | 6.459798e-01 | 0.190 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 6.520032e-01 | 0.186 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 6.533923e-01 | 0.185 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 6.533923e-01 | 0.185 |
| R-HSA-9828806 | Maturation of hRSV A proteins | 6.533923e-01 | 0.185 |
| R-HSA-111885 | Opioid Signalling | 6.594743e-01 | 0.181 |
| R-HSA-9865114 | Maple Syrup Urine Disease | 6.612769e-01 | 0.180 |
| R-HSA-77285 | Beta oxidation of myristoyl-CoA to lauroyl-CoA | 6.612769e-01 | 0.180 |
| R-HSA-9931530 | Phosphorylation and nuclear translocation of the CRY:PER:kinase complex | 6.612769e-01 | 0.180 |
| R-HSA-77305 | Beta oxidation of palmitoyl-CoA to myristoyl-CoA | 6.612769e-01 | 0.180 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 6.612769e-01 | 0.180 |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft | 6.612769e-01 | 0.180 |
| R-HSA-877312 | Regulation of IFNG signaling | 6.612769e-01 | 0.180 |
| R-HSA-9026286 | Biosynthesis of DPAn-3-derived protectins and resolvins | 6.612769e-01 | 0.180 |
| R-HSA-418890 | Role of second messengers in netrin-1 signaling | 6.612769e-01 | 0.180 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 6.612769e-01 | 0.180 |
| R-HSA-9697154 | Disorders of Nervous System Development | 6.612769e-01 | 0.180 |
| R-HSA-9005895 | Pervasive developmental disorders | 6.612769e-01 | 0.180 |
| R-HSA-5687613 | Diseases associated with surfactant metabolism | 6.612769e-01 | 0.180 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 6.693064e-01 | 0.174 |
| R-HSA-5620971 | Pyroptosis | 6.693064e-01 | 0.174 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 6.746248e-01 | 0.171 |
| R-HSA-9694635 | Translation of Structural Proteins | 6.805143e-01 | 0.167 |
| R-HSA-3214858 | RMTs methylate histone arginines | 6.826648e-01 | 0.166 |
| R-HSA-156581 | Methylation | 6.826648e-01 | 0.166 |
| R-HSA-190322 | FGFR4 ligand binding and activation | 6.834483e-01 | 0.165 |
| R-HSA-9853506 | OGDH complex synthesizes succinyl-CoA from 2-OG | 6.834483e-01 | 0.165 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 6.834483e-01 | 0.165 |
| R-HSA-190373 | FGFR1c ligand binding and activation | 6.834483e-01 | 0.165 |
| R-HSA-8949664 | Processing of SMDT1 | 6.834483e-01 | 0.165 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 6.834483e-01 | 0.165 |
| R-HSA-5676594 | TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway | 6.834483e-01 | 0.165 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 6.834483e-01 | 0.165 |
| R-HSA-1475029 | Reversible hydration of carbon dioxide | 6.834483e-01 | 0.165 |
| R-HSA-9683610 | Maturation of nucleoprotein | 6.834483e-01 | 0.165 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 6.846237e-01 | 0.165 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 6.855460e-01 | 0.164 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 6.902415e-01 | 0.161 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 6.949183e-01 | 0.158 |
| R-HSA-774815 | Nucleosome assembly | 6.949183e-01 | 0.158 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 6.993541e-01 | 0.155 |
| R-HSA-112311 | Neurotransmitter clearance | 6.993541e-01 | 0.155 |
| R-HSA-9859138 | BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV | 7.041698e-01 | 0.152 |
| R-HSA-190372 | FGFR3c ligand binding and activation | 7.041698e-01 | 0.152 |
| R-HSA-804914 | Transport of fatty acids | 7.041698e-01 | 0.152 |
| R-HSA-1483115 | Hydrolysis of LPC | 7.041698e-01 | 0.152 |
| R-HSA-9023661 | Biosynthesis of E-series 18(R)-resolvins | 7.041698e-01 | 0.152 |
| R-HSA-77348 | Beta oxidation of octanoyl-CoA to hexanoyl-CoA | 7.041698e-01 | 0.152 |
| R-HSA-69166 | Removal of the Flap Intermediate | 7.041698e-01 | 0.152 |
| R-HSA-77350 | Beta oxidation of hexanoyl-CoA to butanoyl-CoA | 7.041698e-01 | 0.152 |
| R-HSA-77310 | Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA | 7.041698e-01 | 0.152 |
| R-HSA-9686114 | Non-canonical inflammasome activation | 7.041698e-01 | 0.152 |
| R-HSA-9828642 | Respiratory syncytial virus genome transcription | 7.041698e-01 | 0.152 |
| R-HSA-9856872 | Malate-aspartate shuttle | 7.041698e-01 | 0.152 |
| R-HSA-435354 | Zinc transporters | 7.041698e-01 | 0.152 |
| R-HSA-1474290 | Collagen formation | 7.043482e-01 | 0.152 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 7.066052e-01 | 0.151 |
| R-HSA-9839373 | Signaling by TGFBR3 | 7.068107e-01 | 0.151 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 7.068107e-01 | 0.151 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 7.068107e-01 | 0.151 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 7.090841e-01 | 0.149 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 7.135086e-01 | 0.147 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 7.235360e-01 | 0.141 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 7.235360e-01 | 0.141 |
| R-HSA-5654228 | Phospholipase C-mediated cascade; FGFR4 | 7.235360e-01 | 0.141 |
| R-HSA-379401 | Dopamine clearance from the synaptic cleft | 7.235360e-01 | 0.141 |
| R-HSA-2142712 | Synthesis of 12-eicosatetraenoic acid derivatives | 7.235360e-01 | 0.141 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 7.235360e-01 | 0.141 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 7.235360e-01 | 0.141 |
| R-HSA-416700 | Other semaphorin interactions | 7.235360e-01 | 0.141 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 7.235360e-01 | 0.141 |
| R-HSA-597592 | Post-translational protein modification | 7.249878e-01 | 0.140 |
| R-HSA-1538133 | G0 and Early G1 | 7.270997e-01 | 0.138 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 7.293124e-01 | 0.137 |
| R-HSA-9634597 | GPER1 signaling | 7.295225e-01 | 0.137 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 7.358121e-01 | 0.133 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 7.401404e-01 | 0.131 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 7.401404e-01 | 0.131 |
| R-HSA-9733709 | Cardiogenesis | 7.401404e-01 | 0.131 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 7.416354e-01 | 0.130 |
| R-HSA-176412 | Phosphorylation of the APC/C | 7.416354e-01 | 0.130 |
| R-HSA-5083636 | Defective GALNT12 causes CRCS1 | 7.416354e-01 | 0.130 |
| R-HSA-5083625 | Defective GALNT3 causes HFTC | 7.416354e-01 | 0.130 |
| R-HSA-168275 | Entry of Influenza Virion into Host Cell via Endocytosis | 7.416354e-01 | 0.130 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 7.416354e-01 | 0.130 |
| R-HSA-9664420 | Killing mechanisms | 7.416354e-01 | 0.130 |
| R-HSA-9603798 | Class I peroxisomal membrane protein import | 7.416354e-01 | 0.130 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 7.416354e-01 | 0.130 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 7.416354e-01 | 0.130 |
| R-HSA-5635838 | Activation of SMO | 7.416354e-01 | 0.130 |
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand | 7.416354e-01 | 0.130 |
| R-HSA-9678110 | Attachment and Entry | 7.416354e-01 | 0.130 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 7.526092e-01 | 0.123 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 7.585510e-01 | 0.120 |
| R-HSA-77595 | Processing of Intronless Pre-mRNAs | 7.585510e-01 | 0.120 |
| R-HSA-9027307 | Biosynthesis of maresin-like SPMs | 7.585510e-01 | 0.120 |
| R-HSA-77288 | mitochondrial fatty acid beta-oxidation of unsaturated fatty acids | 7.585510e-01 | 0.120 |
| R-HSA-6783984 | Glycine degradation | 7.585510e-01 | 0.120 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 7.585510e-01 | 0.120 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 7.585510e-01 | 0.120 |
| R-HSA-196783 | Coenzyme A biosynthesis | 7.585510e-01 | 0.120 |
| R-HSA-77346 | Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA | 7.585510e-01 | 0.120 |
| R-HSA-1483148 | Synthesis of PG | 7.585510e-01 | 0.120 |
| R-HSA-9675151 | Disorders of Developmental Biology | 7.585510e-01 | 0.120 |
| R-HSA-5661270 | Formation of xylulose-5-phosphate | 7.585510e-01 | 0.120 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 7.646262e-01 | 0.117 |
| R-HSA-1474165 | Reproduction | 7.693969e-01 | 0.114 |
| R-HSA-6794361 | Neurexins and neuroligins | 7.707662e-01 | 0.113 |
| R-HSA-5083632 | Defective C1GALT1C1 causes TNPS | 7.743600e-01 | 0.111 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 7.743600e-01 | 0.111 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 7.743600e-01 | 0.111 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 7.743600e-01 | 0.111 |
| R-HSA-9020265 | Biosynthesis of aspirin-triggered D-series resolvins | 7.743600e-01 | 0.111 |
| R-HSA-2142770 | Synthesis of 15-eicosatetraenoic acid derivatives | 7.743600e-01 | 0.111 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 7.743600e-01 | 0.111 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 7.743600e-01 | 0.111 |
| R-HSA-1614517 | Sulfide oxidation to sulfate | 7.743600e-01 | 0.111 |
| R-HSA-2408550 | Metabolism of ingested H2SeO4 and H2SeO3 into H2Se | 7.743600e-01 | 0.111 |
| R-HSA-381042 | PERK regulates gene expression | 7.761004e-01 | 0.110 |
| R-HSA-193775 | Synthesis of bile acids and bile salts via 24-hydroxycholesterol | 7.761004e-01 | 0.110 |
| R-HSA-8956320 | Nucleotide biosynthesis | 7.802356e-01 | 0.108 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 7.805114e-01 | 0.108 |
| R-HSA-189445 | Metabolism of porphyrins | 7.805114e-01 | 0.108 |
| R-HSA-5358508 | Mismatch Repair | 7.891348e-01 | 0.103 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 7.891348e-01 | 0.103 |
| R-HSA-2142700 | Biosynthesis of Lipoxins (LX) | 7.891348e-01 | 0.103 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 7.891348e-01 | 0.103 |
| R-HSA-9679504 | Translation of Replicase and Assembly of the Replication Transcription Complex | 7.891348e-01 | 0.103 |
| R-HSA-1296072 | Voltage gated Potassium channels | 7.975868e-01 | 0.098 |
| R-HSA-419037 | NCAM1 interactions | 7.975868e-01 | 0.098 |
| R-HSA-8948216 | Collagen chain trimerization | 7.975868e-01 | 0.098 |
| R-HSA-416476 | G alpha (q) signalling events | 8.006494e-01 | 0.097 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 8.029430e-01 | 0.095 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 8.029430e-01 | 0.095 |
| R-HSA-9834899 | Specification of the neural plate border | 8.029430e-01 | 0.095 |
| R-HSA-9913635 | Strand-asynchronous mitochondrial DNA replication | 8.029430e-01 | 0.095 |
| R-HSA-429958 | mRNA decay by 3' to 5' exoribonuclease | 8.029430e-01 | 0.095 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 8.029430e-01 | 0.095 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 8.029430e-01 | 0.095 |
| R-HSA-1237044 | Erythrocytes take up carbon dioxide and release oxygen | 8.029430e-01 | 0.095 |
| R-HSA-9694631 | Maturation of nucleoprotein | 8.029430e-01 | 0.095 |
| R-HSA-1480926 | O2/CO2 exchange in erythrocytes | 8.029430e-01 | 0.095 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 8.051075e-01 | 0.094 |
| R-HSA-9931953 | Biofilm formation | 8.076297e-01 | 0.093 |
| R-HSA-163685 | Integration of energy metabolism | 8.107118e-01 | 0.091 |
| R-HSA-1483166 | Synthesis of PA | 8.149306e-01 | 0.089 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 8.158478e-01 | 0.088 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 8.158478e-01 | 0.088 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 8.158478e-01 | 0.088 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 8.158478e-01 | 0.088 |
| R-HSA-1362409 | Mitochondrial iron-sulfur cluster biogenesis | 8.158478e-01 | 0.088 |
| R-HSA-2022857 | Keratan sulfate degradation | 8.158478e-01 | 0.088 |
| R-HSA-1482922 | Acyl chain remodelling of PI | 8.158478e-01 | 0.088 |
| R-HSA-71288 | Creatine metabolism | 8.158478e-01 | 0.088 |
| R-HSA-9823730 | Formation of definitive endoderm | 8.158478e-01 | 0.088 |
| R-HSA-77111 | Synthesis of Ketone Bodies | 8.158478e-01 | 0.088 |
| R-HSA-9629569 | Protein hydroxylation | 8.158478e-01 | 0.088 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 8.158478e-01 | 0.088 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 8.183718e-01 | 0.087 |
| R-HSA-72306 | tRNA processing | 8.208412e-01 | 0.086 |
| R-HSA-2029481 | FCGR activation | 8.247268e-01 | 0.084 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 8.263916e-01 | 0.083 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 8.263916e-01 | 0.083 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 8.263916e-01 | 0.083 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 8.279081e-01 | 0.082 |
| R-HSA-202040 | G-protein activation | 8.279081e-01 | 0.082 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 8.279081e-01 | 0.082 |
| R-HSA-9018896 | Biosynthesis of E-series 18(S)-resolvins | 8.279081e-01 | 0.082 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 8.279081e-01 | 0.082 |
| R-HSA-196836 | Vitamin C (ascorbate) metabolism | 8.279081e-01 | 0.082 |
| R-HSA-1482925 | Acyl chain remodelling of PG | 8.279081e-01 | 0.082 |
| R-HSA-210991 | Basigin interactions | 8.279081e-01 | 0.082 |
| R-HSA-69186 | Lagging Strand Synthesis | 8.279081e-01 | 0.082 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 8.279081e-01 | 0.082 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 8.304638e-01 | 0.081 |
| R-HSA-216083 | Integrin cell surface interactions | 8.323359e-01 | 0.080 |
| R-HSA-6783783 | Interleukin-10 signaling | 8.323359e-01 | 0.080 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 8.337450e-01 | 0.079 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 8.337450e-01 | 0.079 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 8.337450e-01 | 0.079 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 8.351412e-01 | 0.078 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 8.378020e-01 | 0.077 |
| R-HSA-8873719 | RAB geranylgeranylation | 8.378020e-01 | 0.077 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 8.391794e-01 | 0.076 |
| R-HSA-211979 | Eicosanoids | 8.391794e-01 | 0.076 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 8.391794e-01 | 0.076 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 8.391794e-01 | 0.076 |
| R-HSA-211958 | Miscellaneous substrates | 8.391794e-01 | 0.076 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 8.391794e-01 | 0.076 |
| R-HSA-9694614 | Attachment and Entry | 8.391794e-01 | 0.076 |
| R-HSA-9755088 | Ribavirin ADME | 8.391794e-01 | 0.076 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 8.432232e-01 | 0.074 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 8.434903e-01 | 0.074 |
| R-HSA-8956321 | Nucleotide salvage | 8.448643e-01 | 0.073 |
| R-HSA-388396 | GPCR downstream signalling | 8.455226e-01 | 0.073 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 8.497130e-01 | 0.071 |
| R-HSA-9018676 | Biosynthesis of D-series resolvins | 8.497130e-01 | 0.071 |
| R-HSA-3238698 | WNT ligand biogenesis and trafficking | 8.497130e-01 | 0.071 |
| R-HSA-9694676 | Translation of Replicase and Assembly of the Replication Transcription Complex | 8.497130e-01 | 0.071 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 8.514537e-01 | 0.070 |
| R-HSA-111996 | Ca-dependent events | 8.514537e-01 | 0.070 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 8.581913e-01 | 0.066 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 8.595573e-01 | 0.066 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 8.595573e-01 | 0.066 |
| R-HSA-977068 | Termination of O-glycan biosynthesis | 8.595573e-01 | 0.066 |
| R-HSA-211935 | Fatty acids | 8.595573e-01 | 0.066 |
| R-HSA-74182 | Ketone body metabolism | 8.595573e-01 | 0.066 |
| R-HSA-9830674 | Formation of the ureteric bud | 8.595573e-01 | 0.066 |
| R-HSA-446210 | Synthesis of UDP-N-acetyl-glucosamine | 8.595573e-01 | 0.066 |
| R-HSA-200425 | Carnitine shuttle | 8.595573e-01 | 0.066 |
| R-HSA-3000170 | Syndecan interactions | 8.595573e-01 | 0.066 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 8.675094e-01 | 0.062 |
| R-HSA-211999 | CYP2E1 reactions | 8.687573e-01 | 0.061 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 8.687573e-01 | 0.061 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 8.687573e-01 | 0.061 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 8.687573e-01 | 0.061 |
| R-HSA-1614558 | Degradation of cysteine and homocysteine | 8.731751e-01 | 0.059 |
| R-HSA-1489509 | DAG and IP3 signaling | 8.731751e-01 | 0.059 |
| R-HSA-5619102 | SLC transporter disorders | 8.771165e-01 | 0.057 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 8.773551e-01 | 0.057 |
| R-HSA-9839394 | TGFBR3 expression | 8.773551e-01 | 0.057 |
| R-HSA-1482801 | Acyl chain remodelling of PS | 8.773551e-01 | 0.057 |
| R-HSA-2160916 | Hyaluronan degradation | 8.773551e-01 | 0.057 |
| R-HSA-9027604 | Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives | 8.773551e-01 | 0.057 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 8.797397e-01 | 0.056 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 8.797397e-01 | 0.056 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 8.818630e-01 | 0.055 |
| R-HSA-70635 | Urea cycle | 8.853902e-01 | 0.053 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 8.853902e-01 | 0.053 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 8.853902e-01 | 0.053 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 8.875736e-01 | 0.052 |
| R-HSA-425410 | Metal ion SLC transporters | 8.919363e-01 | 0.050 |
| R-HSA-9025094 | Biosynthesis of DPAn-3 SPMs | 8.928993e-01 | 0.049 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 8.928993e-01 | 0.049 |
| R-HSA-1483213 | Synthesis of PE | 8.928993e-01 | 0.049 |
| R-HSA-9645723 | Diseases of programmed cell death | 8.929171e-01 | 0.049 |
| R-HSA-73886 | Chromosome Maintenance | 8.929535e-01 | 0.049 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 8.929535e-01 | 0.049 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 8.943946e-01 | 0.048 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 8.999168e-01 | 0.046 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 8.999168e-01 | 0.046 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 8.999168e-01 | 0.046 |
| R-HSA-77387 | Insulin receptor recycling | 8.999168e-01 | 0.046 |
| R-HSA-171319 | Telomere Extension By Telomerase | 8.999168e-01 | 0.046 |
| R-HSA-9757110 | Prednisone ADME | 8.999168e-01 | 0.046 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 9.019497e-01 | 0.045 |
| R-HSA-9610379 | HCMV Late Events | 9.042557e-01 | 0.044 |
| R-HSA-72086 | mRNA Capping | 9.064750e-01 | 0.043 |
| R-HSA-5334118 | DNA methylation | 9.064750e-01 | 0.043 |
| R-HSA-9018679 | Biosynthesis of EPA-derived SPMs | 9.064750e-01 | 0.043 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 9.064750e-01 | 0.043 |
| R-HSA-1474244 | Extracellular matrix organization | 9.069006e-01 | 0.042 |
| R-HSA-2514856 | The phototransduction cascade | 9.080911e-01 | 0.042 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 9.126037e-01 | 0.040 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 9.126037e-01 | 0.040 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 9.141109e-01 | 0.039 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 9.175739e-01 | 0.037 |
| R-HSA-399719 | Trafficking of AMPA receptors | 9.183312e-01 | 0.037 |
| R-HSA-9018683 | Biosynthesis of DPA-derived SPMs | 9.183312e-01 | 0.037 |
| R-HSA-8963693 | Aspartate and asparagine metabolism | 9.183312e-01 | 0.037 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 9.189010e-01 | 0.037 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 9.243325e-01 | 0.034 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.246290e-01 | 0.034 |
| R-HSA-15869 | Metabolism of nucleotides | 9.274409e-01 | 0.033 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 9.286857e-01 | 0.032 |
| R-HSA-9930044 | Nuclear RNA decay | 9.286857e-01 | 0.032 |
| R-HSA-159418 | Recycling of bile acids and salts | 9.286857e-01 | 0.032 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 9.286857e-01 | 0.032 |
| R-HSA-5609975 | Diseases associated with glycosylation precursor biosynthesis | 9.286857e-01 | 0.032 |
| R-HSA-73864 | RNA Polymerase I Transcription | 9.298100e-01 | 0.032 |
| R-HSA-8935690 | Digestion | 9.300884e-01 | 0.031 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 9.303824e-01 | 0.031 |
| R-HSA-9843745 | Adipogenesis | 9.315354e-01 | 0.031 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 9.333601e-01 | 0.030 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 9.333601e-01 | 0.030 |
| R-HSA-1482788 | Acyl chain remodelling of PC | 9.333601e-01 | 0.030 |
| R-HSA-1461957 | Beta defensins | 9.333601e-01 | 0.030 |
| R-HSA-2024101 | CS/DS degradation | 9.333601e-01 | 0.030 |
| R-HSA-157579 | Telomere Maintenance | 9.333882e-01 | 0.030 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 9.362759e-01 | 0.029 |
| R-HSA-2142845 | Hyaluronan metabolism | 9.377283e-01 | 0.028 |
| R-HSA-392518 | Signal amplification | 9.377283e-01 | 0.028 |
| R-HSA-3214847 | HATs acetylate histones | 9.390495e-01 | 0.027 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 9.405662e-01 | 0.027 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 9.407910e-01 | 0.027 |
| R-HSA-180786 | Extension of Telomeres | 9.407910e-01 | 0.027 |
| R-HSA-2980736 | Peptide hormone metabolism | 9.408155e-01 | 0.026 |
| R-HSA-917977 | Transferrin endocytosis and recycling | 9.418105e-01 | 0.026 |
| R-HSA-2408508 | Metabolism of ingested SeMet, Sec, MeSec into H2Se | 9.418105e-01 | 0.026 |
| R-HSA-1482839 | Acyl chain remodelling of PE | 9.418105e-01 | 0.026 |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism | 9.418105e-01 | 0.026 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 9.418105e-01 | 0.026 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 9.439987e-01 | 0.025 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 9.456253e-01 | 0.024 |
| R-HSA-9845576 | Glycosphingolipid transport | 9.456253e-01 | 0.024 |
| R-HSA-69205 | G1/S-Specific Transcription | 9.456253e-01 | 0.024 |
| R-HSA-111933 | Calmodulin induced events | 9.456253e-01 | 0.024 |
| R-HSA-111997 | CaM pathway | 9.456253e-01 | 0.024 |
| R-HSA-163560 | Triglyceride catabolism | 9.456253e-01 | 0.024 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 9.467237e-01 | 0.024 |
| R-HSA-112043 | PLC beta mediated events | 9.470406e-01 | 0.024 |
| R-HSA-1442490 | Collagen degradation | 9.470406e-01 | 0.024 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 9.491903e-01 | 0.023 |
| R-HSA-5173214 | O-glycosylation of TSR domain-containing proteins | 9.491903e-01 | 0.023 |
| R-HSA-71064 | Lysine catabolism | 9.491903e-01 | 0.023 |
| R-HSA-196757 | Metabolism of folate and pterines | 9.491903e-01 | 0.023 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 9.499246e-01 | 0.022 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 9.499246e-01 | 0.022 |
| R-HSA-8963743 | Digestion and absorption | 9.526583e-01 | 0.021 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 9.556348e-01 | 0.020 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 9.556348e-01 | 0.020 |
| R-HSA-71336 | Pentose phosphate pathway | 9.556348e-01 | 0.020 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 9.565407e-01 | 0.019 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 9.585440e-01 | 0.018 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 9.585440e-01 | 0.018 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 9.585440e-01 | 0.018 |
| R-HSA-167169 | HIV Transcription Elongation | 9.585440e-01 | 0.018 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 9.585440e-01 | 0.018 |
| R-HSA-71240 | Tryptophan catabolism | 9.585440e-01 | 0.018 |
| R-HSA-9748784 | Drug ADME | 9.597603e-01 | 0.018 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 9.600293e-01 | 0.018 |
| R-HSA-372790 | Signaling by GPCR | 9.610050e-01 | 0.017 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 9.612626e-01 | 0.017 |
| R-HSA-73817 | Purine ribonucleoside monophosphate biosynthesis | 9.612626e-01 | 0.017 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 9.622319e-01 | 0.017 |
| R-HSA-112040 | G-protein mediated events | 9.622319e-01 | 0.017 |
| R-HSA-196807 | Nicotinate metabolism | 9.622319e-01 | 0.017 |
| R-HSA-73884 | Base Excision Repair | 9.631580e-01 | 0.016 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 9.638031e-01 | 0.016 |
| R-HSA-167161 | HIV Transcription Initiation | 9.638031e-01 | 0.016 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 9.638031e-01 | 0.016 |
| R-HSA-6811438 | Intra-Golgi traffic | 9.638031e-01 | 0.016 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 9.638031e-01 | 0.016 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 9.638031e-01 | 0.016 |
| R-HSA-189451 | Heme biosynthesis | 9.638031e-01 | 0.016 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.641523e-01 | 0.016 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 9.661771e-01 | 0.015 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 9.661771e-01 | 0.015 |
| R-HSA-375276 | Peptide ligand-binding receptors | 9.667366e-01 | 0.015 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 9.681619e-01 | 0.014 |
| R-HSA-204005 | COPII-mediated vesicle transport | 9.681619e-01 | 0.014 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 9.681619e-01 | 0.014 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 9.681619e-01 | 0.014 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 9.683956e-01 | 0.014 |
| R-HSA-9710421 | Defective pyroptosis | 9.683956e-01 | 0.014 |
| R-HSA-1461973 | Defensins | 9.683956e-01 | 0.014 |
| R-HSA-375280 | Amine ligand-binding receptors | 9.704686e-01 | 0.013 |
| R-HSA-196741 | Cobalamin (Cbl, vitamin B12) transport and metabolism | 9.704686e-01 | 0.013 |
| R-HSA-5683826 | Surfactant metabolism | 9.704686e-01 | 0.013 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 9.721176e-01 | 0.012 |
| R-HSA-418555 | G alpha (s) signalling events | 9.723944e-01 | 0.012 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 9.724058e-01 | 0.012 |
| R-HSA-77286 | mitochondrial fatty acid beta-oxidation of saturated fatty acids | 9.724058e-01 | 0.012 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 9.724058e-01 | 0.012 |
| R-HSA-3560782 | Diseases associated with glycosaminoglycan metabolism | 9.724058e-01 | 0.012 |
| R-HSA-2142753 | Arachidonate metabolism | 9.727985e-01 | 0.012 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 9.742160e-01 | 0.011 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.745103e-01 | 0.011 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.745103e-01 | 0.011 |
| R-HSA-425397 | Transport of vitamins, nucleosides, and related molecules | 9.746886e-01 | 0.011 |
| R-HSA-1483191 | Synthesis of PC | 9.759076e-01 | 0.011 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 9.774468e-01 | 0.010 |
| R-HSA-9031628 | NGF-stimulated transcription | 9.774883e-01 | 0.010 |
| R-HSA-1638074 | Keratan sulfate/keratin metabolism | 9.789654e-01 | 0.009 |
| R-HSA-380108 | Chemokine receptors bind chemokines | 9.789654e-01 | 0.009 |
| R-HSA-389661 | Glyoxylate metabolism and glycine degradation | 9.789654e-01 | 0.009 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.790742e-01 | 0.009 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 9.793327e-01 | 0.009 |
| R-HSA-877300 | Interferon gamma signaling | 9.797683e-01 | 0.009 |
| R-HSA-191273 | Cholesterol biosynthesis | 9.799131e-01 | 0.009 |
| R-HSA-912446 | Meiotic recombination | 9.816354e-01 | 0.008 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 9.828406e-01 | 0.008 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 9.828406e-01 | 0.008 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 9.831290e-01 | 0.007 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 9.839667e-01 | 0.007 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 9.847318e-01 | 0.007 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 9.847318e-01 | 0.007 |
| R-HSA-1793185 | Chondroitin sulfate/dermatan sulfate metabolism | 9.860024e-01 | 0.006 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 9.872364e-01 | 0.006 |
| R-HSA-1614635 | Sulfur amino acid metabolism | 9.881294e-01 | 0.005 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 9.881294e-01 | 0.005 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.889066e-01 | 0.005 |
| R-HSA-8979227 | Triglyceride metabolism | 9.893316e-01 | 0.005 |
| R-HSA-1483257 | Phospholipid metabolism | 9.895430e-01 | 0.005 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.899715e-01 | 0.004 |
| R-HSA-977443 | GABA receptor activation | 9.900321e-01 | 0.004 |
| R-HSA-211976 | Endogenous sterols | 9.906866e-01 | 0.004 |
| R-HSA-445717 | Aquaporin-mediated transport | 9.906866e-01 | 0.004 |
| R-HSA-382551 | Transport of small molecules | 9.913572e-01 | 0.004 |
| R-HSA-211981 | Xenobiotics | 9.924035e-01 | 0.003 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 9.924035e-01 | 0.003 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.928032e-01 | 0.003 |
| R-HSA-418594 | G alpha (i) signalling events | 9.940369e-01 | 0.003 |
| R-HSA-5389840 | Mitochondrial translation elongation | 9.941766e-01 | 0.003 |
| R-HSA-1296071 | Potassium Channels | 9.941766e-01 | 0.003 |
| R-HSA-913709 | O-linked glycosylation of mucins | 9.942112e-01 | 0.003 |
| R-HSA-167172 | Transcription of the HIV genome | 9.942112e-01 | 0.003 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 9.942112e-01 | 0.003 |
| R-HSA-5368286 | Mitochondrial translation initiation | 9.948338e-01 | 0.002 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 9.949468e-01 | 0.002 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 9.952788e-01 | 0.002 |
| R-HSA-975634 | Retinoid metabolism and transport | 9.952788e-01 | 0.002 |
| R-HSA-6809371 | Formation of the cornified envelope | 9.953520e-01 | 0.002 |
| R-HSA-74259 | Purine catabolism | 9.955890e-01 | 0.002 |
| R-HSA-9749641 | Aspirin ADME | 9.958788e-01 | 0.002 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 9.961497e-01 | 0.002 |
| R-HSA-1222556 | ROS and RNS production in phagocytes | 9.961497e-01 | 0.002 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 9.961750e-01 | 0.002 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 9.972592e-01 | 0.001 |
| R-HSA-5419276 | Mitochondrial translation termination | 9.974956e-01 | 0.001 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 9.976077e-01 | 0.001 |
| R-HSA-390918 | Peroxisomal lipid metabolism | 9.980492e-01 | 0.001 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 9.984093e-01 | 0.001 |
| R-HSA-8957322 | Metabolism of steroids | 9.984487e-01 | 0.001 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 9.986354e-01 | 0.001 |
| R-HSA-112310 | Neurotransmitter release cycle | 9.987883e-01 | 0.001 |
| R-HSA-2187338 | Visual phototransduction | 9.989804e-01 | 0.000 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.991413e-01 | 0.000 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 9.991945e-01 | 0.000 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.991995e-01 | 0.000 |
| R-HSA-611105 | Respiratory electron transport | 9.992261e-01 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 9.993155e-01 | 0.000 |
| R-HSA-422356 | Regulation of insulin secretion | 9.993866e-01 | 0.000 |
| R-HSA-163125 | Post-translational modification: synthesis of GPI-anchored proteins | 9.996192e-01 | 0.000 |
| R-HSA-5173105 | O-linked glycosylation | 9.996715e-01 | 0.000 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 9.996789e-01 | 0.000 |
| R-HSA-5368287 | Mitochondrial translation | 9.996914e-01 | 0.000 |
| R-HSA-6803157 | Antimicrobial peptides | 9.997636e-01 | 0.000 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 9.997878e-01 | 0.000 |
| R-HSA-3781865 | Diseases of glycosylation | 9.998885e-01 | 0.000 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 9.999090e-01 | 0.000 |
| R-HSA-977606 | Regulation of Complement cascade | 9.999206e-01 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 9.999300e-01 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.999390e-01 | 0.000 |
| R-HSA-8956319 | Nucleotide catabolism | 9.999435e-01 | 0.000 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 9.999540e-01 | 0.000 |
| R-HSA-428157 | Sphingolipid metabolism | 9.999595e-01 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 9.999616e-01 | 0.000 |
| R-HSA-6805567 | Keratinization | 9.999718e-01 | 0.000 |
| R-HSA-166658 | Complement cascade | 9.999846e-01 | 0.000 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.999932e-01 | 0.000 |
| R-HSA-9640148 | Infection with Enterobacteria | 9.999956e-01 | 0.000 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.999976e-01 | 0.000 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 9.999992e-01 | 0.000 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 9.999995e-01 | 0.000 |
| R-HSA-211859 | Biological oxidations | 9.999999e-01 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 1.000000e+00 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | 0.000 |
| R-HSA-9752946 | Expression and translocation of olfactory receptors | 1.000000e+00 | -0.000 |
| R-HSA-381753 | Olfactory Signaling Pathway | 1.000000e+00 | -0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | -0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
PDHK3_TYR |
0.831 | 0.061 | 4 | 0.948 |
MAP2K4_TYR |
0.821 | -0.061 | -1 | 0.919 |
TESK1_TYR |
0.821 | -0.070 | 3 | 0.898 |
PKMYT1_TYR |
0.820 | -0.052 | 3 | 0.882 |
PDHK4_TYR |
0.819 | -0.060 | 2 | 0.921 |
MAP2K7_TYR |
0.819 | -0.119 | 2 | 0.916 |
MAP2K6_TYR |
0.819 | -0.086 | -1 | 0.917 |
BMPR2_TYR |
0.818 | -0.044 | -1 | 0.896 |
PDHK1_TYR |
0.818 | -0.057 | -1 | 0.926 |
EPHA6 |
0.818 | 0.005 | -1 | 0.894 |
EPHB4 |
0.817 | 0.018 | -1 | 0.883 |
PINK1_TYR |
0.816 | -0.121 | 1 | 0.862 |
LIMK2_TYR |
0.814 | -0.041 | -3 | 0.924 |
TYK2 |
0.814 | -0.013 | 1 | 0.834 |
MST1R |
0.813 | -0.005 | 3 | 0.855 |
RET |
0.813 | -0.058 | 1 | 0.832 |
TYRO3 |
0.813 | -0.027 | 3 | 0.836 |
ROS1 |
0.812 | -0.022 | 3 | 0.818 |
FER |
0.811 | -0.004 | 1 | 0.926 |
GAK |
0.810 | 0.000 | 1 | 0.883 |
LIMK1_TYR |
0.810 | -0.094 | 2 | 0.916 |
JAK2 |
0.810 | -0.018 | 1 | 0.827 |
CSF1R |
0.810 | -0.036 | 3 | 0.840 |
EPHB1 |
0.810 | 0.043 | 1 | 0.898 |
YES1 |
0.810 | -0.020 | -1 | 0.882 |
ABL2 |
0.809 | -0.008 | -1 | 0.860 |
DDR1 |
0.809 | -0.085 | 4 | 0.889 |
EPHA4 |
0.809 | 0.025 | 2 | 0.822 |
TXK |
0.809 | 0.019 | 1 | 0.884 |
FGR |
0.809 | -0.018 | 1 | 0.898 |
HCK |
0.808 | 0.029 | -1 | 0.857 |
EPHB3 |
0.808 | 0.027 | -1 | 0.867 |
TNK2 |
0.808 | -0.005 | 3 | 0.823 |
SRMS |
0.808 | 0.007 | 1 | 0.908 |
TSSK2 |
0.808 | 0.361 | -5 | 0.340 |
EPHB2 |
0.807 | 0.031 | -1 | 0.860 |
INSRR |
0.806 | -0.034 | 3 | 0.804 |
ABL1 |
0.806 | 0.000 | -1 | 0.853 |
PKR |
0.806 | -0.022 | 1 | 0.870 |
VRK2 |
0.805 | -0.105 | 1 | 0.894 |
LCK |
0.805 | 0.017 | -1 | 0.854 |
BUB1 |
0.804 | 0.411 | -5 | 0.463 |
BLK |
0.804 | 0.017 | -1 | 0.864 |
NIK |
0.804 | 0.069 | -3 | 0.924 |
TNNI3K_TYR |
0.804 | 0.022 | 1 | 0.849 |
PDGFRB |
0.803 | -0.056 | 3 | 0.852 |
ITK |
0.803 | -0.035 | -1 | 0.834 |
MERTK |
0.803 | 0.011 | 3 | 0.822 |
FLT3 |
0.803 | -0.030 | 3 | 0.837 |
CHK1 |
0.802 | 0.321 | -3 | 0.876 |
BMPR2 |
0.802 | -0.054 | -2 | 0.910 |
JAK3 |
0.802 | -0.074 | 1 | 0.806 |
AXL |
0.802 | -0.017 | 3 | 0.828 |
DAPK2 |
0.802 | 0.037 | -3 | 0.901 |
FGFR2 |
0.802 | -0.061 | 3 | 0.846 |
EPHA7 |
0.802 | 0.019 | 2 | 0.836 |
KIT |
0.802 | -0.057 | 3 | 0.844 |
CAMK1B |
0.801 | 0.125 | -3 | 0.901 |
LTK |
0.800 | -0.008 | 3 | 0.797 |
KDR |
0.800 | -0.055 | 3 | 0.813 |
TEC |
0.800 | 0.003 | -1 | 0.791 |
ALK |
0.800 | -0.017 | 3 | 0.778 |
TEK |
0.800 | -0.048 | 3 | 0.791 |
ALK4 |
0.799 | 0.037 | -2 | 0.863 |
PDGFRA |
0.799 | -0.034 | 3 | 0.847 |
JAK1 |
0.799 | 0.004 | 1 | 0.763 |
FRK |
0.799 | 0.027 | -1 | 0.876 |
EPHA1 |
0.799 | 0.024 | 3 | 0.818 |
TNK1 |
0.799 | -0.035 | 3 | 0.815 |
BMX |
0.799 | 0.002 | -1 | 0.762 |
FYN |
0.799 | 0.019 | -1 | 0.825 |
CAMLCK |
0.798 | 0.017 | -2 | 0.881 |
BRAF |
0.798 | -0.045 | -4 | 0.879 |
EEF2K |
0.798 | 0.001 | 3 | 0.854 |
FGFR1 |
0.798 | -0.054 | 3 | 0.821 |
BIKE |
0.798 | 0.068 | 1 | 0.762 |
EPHA3 |
0.798 | -0.003 | 2 | 0.808 |
MOS |
0.798 | 0.040 | 1 | 0.916 |
TTK |
0.798 | 0.002 | -2 | 0.842 |
MEK1 |
0.798 | -0.066 | 2 | 0.896 |
VRK1 |
0.797 | -0.117 | 2 | 0.900 |
BTK |
0.797 | -0.047 | -1 | 0.806 |
LRRK2 |
0.797 | -0.078 | 2 | 0.909 |
NEK1 |
0.797 | -0.006 | 1 | 0.825 |
NTRK1 |
0.797 | -0.056 | -1 | 0.863 |
PRPK |
0.796 | -0.073 | -1 | 0.900 |
MET |
0.796 | -0.066 | 3 | 0.831 |
TAK1 |
0.796 | -0.088 | 1 | 0.853 |
LYN |
0.795 | 0.005 | 3 | 0.770 |
EPHA5 |
0.795 | 0.019 | 2 | 0.817 |
PTK2B |
0.794 | 0.017 | -1 | 0.824 |
NEK5 |
0.794 | -0.049 | 1 | 0.853 |
MEKK2 |
0.793 | -0.078 | 2 | 0.872 |
TSSK1 |
0.793 | 0.280 | -3 | 0.909 |
PTK6 |
0.793 | -0.067 | -1 | 0.769 |
WEE1_TYR |
0.793 | -0.032 | -1 | 0.790 |
MINK |
0.793 | -0.061 | 1 | 0.816 |
ERBB2 |
0.793 | -0.045 | 1 | 0.810 |
TNIK |
0.793 | -0.048 | 3 | 0.869 |
LATS1 |
0.793 | -0.008 | -3 | 0.901 |
GCK |
0.792 | -0.067 | 1 | 0.822 |
NTRK2 |
0.792 | -0.059 | 3 | 0.813 |
MST2 |
0.792 | -0.051 | 1 | 0.838 |
ANKRD3 |
0.792 | -0.050 | 1 | 0.876 |
CDKL1 |
0.792 | 0.033 | -3 | 0.836 |
ALK2 |
0.792 | 0.042 | -2 | 0.838 |
AAK1 |
0.792 | 0.099 | 1 | 0.656 |
DDR2 |
0.791 | -0.025 | 3 | 0.800 |
INSR |
0.791 | -0.055 | 3 | 0.779 |
MEK5 |
0.791 | -0.130 | 2 | 0.885 |
PDK1 |
0.791 | -0.076 | 1 | 0.803 |
TAO2 |
0.791 | -0.066 | 2 | 0.912 |
EPHA8 |
0.791 | -0.003 | -1 | 0.839 |
SMMLCK |
0.791 | 0.027 | -3 | 0.853 |
ATR |
0.790 | -0.019 | 1 | 0.848 |
NTRK3 |
0.790 | -0.037 | -1 | 0.814 |
NEK10_TYR |
0.790 | -0.096 | 1 | 0.684 |
NLK |
0.790 | 0.007 | 1 | 0.832 |
DLK |
0.790 | -0.089 | 1 | 0.863 |
FLT1 |
0.790 | -0.085 | -1 | 0.862 |
FGFR3 |
0.790 | -0.081 | 3 | 0.823 |
TGFBR1 |
0.789 | 0.045 | -2 | 0.836 |
FLT4 |
0.789 | -0.079 | 3 | 0.807 |
ASK1 |
0.789 | -0.104 | 1 | 0.773 |
MST1 |
0.789 | -0.070 | 1 | 0.820 |
MAP3K15 |
0.789 | -0.078 | 1 | 0.786 |
SRC |
0.789 | -0.016 | -1 | 0.832 |
HGK |
0.789 | -0.050 | 3 | 0.875 |
CSK |
0.789 | -0.031 | 2 | 0.839 |
PASK |
0.788 | 0.012 | -3 | 0.889 |
SKMLCK |
0.788 | 0.013 | -2 | 0.882 |
EGFR |
0.788 | -0.016 | 1 | 0.725 |
MATK |
0.787 | -0.060 | -1 | 0.786 |
KHS1 |
0.787 | -0.047 | 1 | 0.801 |
DAPK3 |
0.787 | 0.024 | -3 | 0.844 |
BMPR1B |
0.787 | 0.057 | 1 | 0.859 |
MEKK1 |
0.786 | -0.125 | 1 | 0.837 |
TAO3 |
0.786 | -0.074 | 1 | 0.816 |
ALPHAK3 |
0.786 | -0.047 | -1 | 0.813 |
ICK |
0.786 | 0.020 | -3 | 0.868 |
DMPK1 |
0.786 | 0.033 | -3 | 0.804 |
MEKK6 |
0.785 | -0.067 | 1 | 0.824 |
AMPKA1 |
0.785 | 0.121 | -3 | 0.894 |
ERK5 |
0.785 | 0.048 | 1 | 0.828 |
LKB1 |
0.784 | -0.118 | -3 | 0.860 |
NEK4 |
0.784 | -0.077 | 1 | 0.813 |
KHS2 |
0.784 | -0.029 | 1 | 0.810 |
ACVR2A |
0.784 | 0.035 | -2 | 0.817 |
RAF1 |
0.784 | -0.061 | 1 | 0.873 |
MST3 |
0.784 | -0.053 | 2 | 0.874 |
PTK2 |
0.784 | 0.006 | -1 | 0.796 |
NEK8 |
0.784 | -0.103 | 2 | 0.884 |
CAMKK1 |
0.784 | -0.135 | -2 | 0.798 |
MPSK1 |
0.784 | 0.000 | 1 | 0.814 |
COT |
0.783 | -0.016 | 2 | 0.926 |
NUAK2 |
0.783 | 0.121 | -3 | 0.880 |
ACVR2B |
0.783 | 0.016 | -2 | 0.827 |
MEKK3 |
0.783 | -0.099 | 1 | 0.824 |
CAMKK2 |
0.783 | -0.135 | -2 | 0.797 |
PKN3 |
0.783 | 0.062 | -3 | 0.868 |
PRKD1 |
0.783 | 0.342 | -3 | 0.851 |
P38A |
0.783 | 0.029 | 1 | 0.701 |
EPHA2 |
0.783 | 0.002 | -1 | 0.805 |
WNK1 |
0.782 | 0.061 | -2 | 0.904 |
HPK1 |
0.782 | -0.060 | 1 | 0.800 |
YSK4 |
0.782 | -0.088 | 1 | 0.799 |
PBK |
0.782 | -0.011 | 1 | 0.811 |
GRK6 |
0.782 | -0.002 | 1 | 0.890 |
SYK |
0.782 | -0.002 | -1 | 0.792 |
FGFR4 |
0.781 | -0.041 | -1 | 0.812 |
MYO3B |
0.781 | -0.050 | 2 | 0.875 |
ZAK |
0.781 | -0.081 | 1 | 0.809 |
CAMK2G |
0.781 | -0.012 | 2 | 0.885 |
PERK |
0.781 | -0.035 | -2 | 0.855 |
OSR1 |
0.781 | -0.098 | 2 | 0.855 |
YSK1 |
0.780 | -0.064 | 2 | 0.863 |
NEK11 |
0.780 | -0.132 | 1 | 0.803 |
PLK1 |
0.780 | -0.032 | -2 | 0.842 |
PIM1 |
0.779 | 0.051 | -3 | 0.828 |
HRI |
0.779 | -0.033 | -2 | 0.875 |
WNK4 |
0.779 | 0.006 | -2 | 0.898 |
MEK2 |
0.779 | -0.138 | 2 | 0.873 |
JNK2 |
0.779 | 0.011 | 1 | 0.601 |
PDHK4 |
0.779 | -0.096 | 1 | 0.873 |
MYO3A |
0.778 | -0.082 | 1 | 0.801 |
CDC7 |
0.778 | 0.036 | 1 | 0.897 |
MUSK |
0.778 | -0.029 | 1 | 0.713 |
CAMK2D |
0.778 | 0.121 | -3 | 0.870 |
MLK2 |
0.778 | -0.098 | 2 | 0.877 |
PRKD3 |
0.778 | 0.247 | -3 | 0.779 |
IGF1R |
0.777 | -0.056 | 3 | 0.721 |
BMPR1A |
0.777 | 0.057 | 1 | 0.846 |
PRP4 |
0.777 | -0.009 | -3 | 0.795 |
MLK1 |
0.777 | -0.076 | 2 | 0.875 |
PDHK1 |
0.777 | -0.062 | 1 | 0.867 |
JNK3 |
0.777 | -0.018 | 1 | 0.643 |
NEK9 |
0.777 | -0.079 | 2 | 0.896 |
GRK5 |
0.777 | -0.078 | -3 | 0.899 |
P38B |
0.776 | 0.021 | 1 | 0.631 |
ROCK2 |
0.776 | -0.016 | -3 | 0.831 |
PIM3 |
0.776 | -0.011 | -3 | 0.882 |
DSTYK |
0.775 | -0.032 | 2 | 0.929 |
AMPKA2 |
0.775 | 0.106 | -3 | 0.864 |
CDKL5 |
0.775 | 0.042 | -3 | 0.822 |
MAPKAPK3 |
0.775 | 0.111 | -3 | 0.813 |
RIPK1 |
0.775 | -0.044 | 1 | 0.826 |
TLK1 |
0.775 | -0.030 | -2 | 0.844 |
RIPK3 |
0.775 | -0.021 | 3 | 0.809 |
DAPK1 |
0.775 | 0.016 | -3 | 0.822 |
MASTL |
0.775 | -0.121 | -2 | 0.837 |
STLK3 |
0.774 | -0.138 | 1 | 0.775 |
PKN2 |
0.774 | 0.057 | -3 | 0.880 |
ERBB4 |
0.774 | -0.020 | 1 | 0.752 |
CLK3 |
0.774 | 0.037 | 1 | 0.864 |
TLK2 |
0.774 | -0.071 | 1 | 0.827 |
PKCD |
0.774 | 0.014 | 2 | 0.866 |
DCAMKL2 |
0.773 | 0.053 | -3 | 0.853 |
IRAK4 |
0.773 | -0.045 | 1 | 0.824 |
DCAMKL1 |
0.773 | 0.018 | -3 | 0.832 |
MARK4 |
0.772 | 0.051 | 4 | 0.901 |
LOK |
0.772 | -0.075 | -2 | 0.805 |
CAMK1D |
0.772 | 0.132 | -3 | 0.727 |
CAMK4 |
0.772 | 0.101 | -3 | 0.865 |
CHAK2 |
0.772 | -0.059 | -1 | 0.888 |
NEK2 |
0.771 | -0.056 | 2 | 0.873 |
CHK2 |
0.771 | 0.118 | -3 | 0.669 |
GRK7 |
0.771 | -0.016 | 1 | 0.819 |
CAMK2B |
0.770 | 0.121 | 2 | 0.845 |
MELK |
0.770 | 0.105 | -3 | 0.845 |
ATM |
0.769 | 0.011 | 1 | 0.788 |
TGFBR2 |
0.769 | 0.001 | -2 | 0.825 |
P70S6KB |
0.769 | -0.028 | -3 | 0.838 |
PIM2 |
0.769 | -0.005 | -3 | 0.782 |
PRKD2 |
0.768 | 0.213 | -3 | 0.807 |
MYLK4 |
0.768 | 0.038 | -2 | 0.795 |
FES |
0.768 | -0.028 | -1 | 0.739 |
P90RSK |
0.768 | 0.045 | -3 | 0.809 |
HUNK |
0.768 | -0.056 | 2 | 0.864 |
RSK2 |
0.767 | 0.039 | -3 | 0.807 |
TBK1 |
0.767 | -0.056 | 1 | 0.760 |
MST4 |
0.767 | -0.012 | 2 | 0.881 |
CAMK2A |
0.767 | 0.119 | 2 | 0.859 |
CAMK1A |
0.767 | 0.170 | -3 | 0.697 |
ERK2 |
0.767 | -0.016 | 1 | 0.657 |
MLK3 |
0.766 | -0.033 | 2 | 0.814 |
PLK3 |
0.766 | -0.028 | 2 | 0.835 |
MRCKA |
0.766 | 0.002 | -3 | 0.800 |
MLK4 |
0.765 | -0.065 | 2 | 0.796 |
WNK3 |
0.765 | -0.105 | 1 | 0.840 |
PINK1 |
0.765 | -0.083 | 1 | 0.840 |
HIPK1 |
0.765 | 0.005 | 1 | 0.711 |
ULK2 |
0.765 | -0.102 | 2 | 0.862 |
MTOR |
0.765 | -0.102 | 1 | 0.795 |
SGK3 |
0.765 | 0.007 | -3 | 0.800 |
CRIK |
0.765 | 0.007 | -3 | 0.736 |
SSTK |
0.765 | 0.090 | 4 | 0.870 |
TAO1 |
0.764 | -0.068 | 1 | 0.739 |
NEK7 |
0.764 | -0.096 | -3 | 0.862 |
DNAPK |
0.764 | 0.004 | 1 | 0.702 |
SMG1 |
0.764 | -0.020 | 1 | 0.793 |
MAPKAPK2 |
0.763 | 0.102 | -3 | 0.774 |
IRE1 |
0.763 | -0.022 | 1 | 0.817 |
ROCK1 |
0.763 | -0.021 | -3 | 0.797 |
NUAK1 |
0.762 | 0.134 | -3 | 0.839 |
IRE2 |
0.762 | -0.036 | 2 | 0.832 |
QIK |
0.762 | 0.074 | -3 | 0.865 |
DYRK2 |
0.762 | -0.000 | 1 | 0.693 |
CAMK1G |
0.762 | 0.089 | -3 | 0.799 |
P38G |
0.762 | -0.012 | 1 | 0.531 |
MRCKB |
0.761 | -0.003 | -3 | 0.781 |
NEK3 |
0.761 | -0.067 | 1 | 0.776 |
GRK2 |
0.761 | -0.038 | -2 | 0.717 |
NEK6 |
0.761 | -0.051 | -2 | 0.891 |
ERK1 |
0.761 | -0.002 | 1 | 0.613 |
HIPK4 |
0.760 | 0.015 | 1 | 0.791 |
MARK2 |
0.760 | 0.063 | 4 | 0.804 |
CLK4 |
0.760 | 0.020 | -3 | 0.808 |
DRAK1 |
0.760 | -0.057 | 1 | 0.774 |
LATS2 |
0.760 | -0.019 | -5 | 0.094 |
NDR1 |
0.760 | -0.040 | -3 | 0.882 |
IKKE |
0.760 | -0.075 | 1 | 0.757 |
CDK5 |
0.760 | -0.015 | 1 | 0.689 |
HASPIN |
0.760 | -0.020 | -1 | 0.744 |
SLK |
0.759 | -0.090 | -2 | 0.739 |
CHAK1 |
0.759 | -0.114 | 2 | 0.827 |
IRAK1 |
0.759 | -0.088 | -1 | 0.794 |
PKCA |
0.759 | -0.007 | 2 | 0.805 |
HIPK3 |
0.759 | 0.013 | 1 | 0.703 |
P38D |
0.758 | 0.007 | 1 | 0.545 |
PKCH |
0.758 | -0.011 | 2 | 0.805 |
PAK2 |
0.758 | -0.046 | -2 | 0.793 |
CDK14 |
0.758 | 0.022 | 1 | 0.639 |
DYRK1A |
0.757 | 0.004 | 1 | 0.729 |
MAK |
0.757 | 0.028 | -2 | 0.785 |
QSK |
0.757 | 0.069 | 4 | 0.876 |
SBK |
0.757 | 0.078 | -3 | 0.600 |
PAK1 |
0.757 | -0.038 | -2 | 0.809 |
AKT2 |
0.757 | 0.012 | -3 | 0.723 |
GRK1 |
0.757 | -0.034 | -2 | 0.774 |
TTBK2 |
0.757 | -0.110 | 2 | 0.781 |
PKCZ |
0.757 | -0.028 | 2 | 0.850 |
MNK2 |
0.756 | 0.070 | -2 | 0.830 |
RSK3 |
0.756 | 0.010 | -3 | 0.806 |
IKKB |
0.756 | -0.097 | -2 | 0.778 |
CDK1 |
0.756 | -0.011 | 1 | 0.623 |
SRPK3 |
0.755 | 0.005 | -3 | 0.762 |
SRPK1 |
0.755 | 0.018 | -3 | 0.785 |
JNK1 |
0.755 | -0.021 | 1 | 0.596 |
NIM1 |
0.755 | -0.031 | 3 | 0.814 |
GRK4 |
0.754 | -0.079 | -2 | 0.818 |
PAK3 |
0.754 | -0.047 | -2 | 0.811 |
MOK |
0.754 | 0.009 | 1 | 0.732 |
PKCB |
0.754 | -0.011 | 2 | 0.811 |
MARK1 |
0.754 | 0.044 | 4 | 0.859 |
PLK2 |
0.753 | 0.006 | -3 | 0.869 |
ERK7 |
0.753 | -0.001 | 2 | 0.598 |
GCN2 |
0.753 | -0.097 | 2 | 0.869 |
CLK1 |
0.753 | 0.034 | -3 | 0.785 |
AURB |
0.753 | 0.009 | -2 | 0.687 |
MSK1 |
0.753 | 0.026 | -3 | 0.784 |
MARK3 |
0.753 | 0.057 | 4 | 0.838 |
NDR2 |
0.753 | -0.032 | -3 | 0.889 |
MNK1 |
0.752 | 0.037 | -2 | 0.835 |
RSK4 |
0.752 | 0.003 | -3 | 0.783 |
GSK3B |
0.752 | -0.010 | 4 | 0.469 |
CDK8 |
0.752 | -0.008 | 1 | 0.661 |
PKACG |
0.751 | -0.016 | -2 | 0.776 |
PKCG |
0.751 | -0.030 | 2 | 0.814 |
CDK18 |
0.751 | 0.024 | 1 | 0.594 |
CDK2 |
0.750 | -0.032 | 1 | 0.719 |
SIK |
0.750 | 0.077 | -3 | 0.806 |
SGK1 |
0.750 | 0.001 | -3 | 0.642 |
MSK2 |
0.750 | 0.003 | -3 | 0.775 |
AKT1 |
0.750 | 0.013 | -3 | 0.743 |
DYRK1B |
0.750 | -0.015 | 1 | 0.645 |
CDK16 |
0.750 | 0.026 | 1 | 0.560 |
BCKDK |
0.749 | -0.072 | -1 | 0.848 |
DYRK3 |
0.749 | 0.002 | 1 | 0.713 |
ULK1 |
0.749 | -0.117 | -3 | 0.846 |
PKG2 |
0.749 | 0.010 | -2 | 0.715 |
GSK3A |
0.749 | -0.008 | 4 | 0.479 |
IKKA |
0.748 | -0.069 | -2 | 0.767 |
ZAP70 |
0.748 | -0.070 | -1 | 0.717 |
CDK17 |
0.748 | -0.000 | 1 | 0.539 |
PLK4 |
0.748 | -0.062 | 2 | 0.721 |
RIPK2 |
0.748 | -0.088 | 1 | 0.755 |
CDK13 |
0.748 | -0.019 | 1 | 0.635 |
CDK7 |
0.746 | -0.020 | 1 | 0.666 |
PKCI |
0.746 | 0.007 | 2 | 0.816 |
PKCE |
0.746 | 0.011 | 2 | 0.795 |
PHKG1 |
0.746 | 0.024 | -3 | 0.869 |
P70S6K |
0.746 | -0.026 | -3 | 0.741 |
MAPKAPK5 |
0.745 | 0.030 | -3 | 0.745 |
CDK6 |
0.745 | -0.021 | 1 | 0.614 |
PKCT |
0.744 | -0.013 | 2 | 0.814 |
CDK12 |
0.744 | -0.018 | 1 | 0.604 |
CDK4 |
0.743 | -0.023 | 1 | 0.594 |
AURA |
0.743 | -0.005 | -2 | 0.650 |
PKN1 |
0.742 | 0.069 | -3 | 0.754 |
AURC |
0.741 | 0.010 | -2 | 0.690 |
HIPK2 |
0.741 | -0.000 | 1 | 0.595 |
DYRK4 |
0.741 | -0.006 | 1 | 0.612 |
CDK3 |
0.740 | -0.008 | 1 | 0.560 |
CDK9 |
0.740 | -0.037 | 1 | 0.642 |
PKACB |
0.740 | 0.007 | -2 | 0.711 |
FAM20C |
0.740 | 0.039 | 2 | 0.640 |
SRPK2 |
0.739 | 0.009 | -3 | 0.709 |
CDK19 |
0.739 | -0.009 | 1 | 0.619 |
BRSK2 |
0.739 | 0.003 | -3 | 0.855 |
GRK3 |
0.739 | -0.027 | -2 | 0.664 |
BRSK1 |
0.738 | 0.002 | -3 | 0.836 |
STK33 |
0.738 | -0.116 | 2 | 0.694 |
CDK10 |
0.736 | -0.006 | 1 | 0.621 |
TTBK1 |
0.736 | -0.071 | 2 | 0.702 |
SNRK |
0.736 | -0.091 | 2 | 0.773 |
PAK6 |
0.736 | 0.038 | -2 | 0.740 |
CLK2 |
0.733 | 0.016 | -3 | 0.796 |
PHKG2 |
0.733 | 0.021 | -3 | 0.842 |
PKACA |
0.733 | 0.015 | -2 | 0.661 |
CK1D |
0.732 | -0.019 | -3 | 0.518 |
CK2A2 |
0.732 | 0.022 | 1 | 0.755 |
CK1A2 |
0.729 | -0.016 | -3 | 0.517 |
AKT3 |
0.728 | -0.003 | -3 | 0.656 |
KIS |
0.727 | 0.006 | 1 | 0.687 |
CK1E |
0.727 | -0.027 | -3 | 0.573 |
CK2A1 |
0.721 | 0.005 | 1 | 0.729 |
PRKX |
0.720 | 0.018 | -3 | 0.726 |
YANK3 |
0.720 | -0.033 | 2 | 0.454 |
PAK5 |
0.717 | -0.017 | -2 | 0.666 |
PAK4 |
0.707 | -0.019 | -2 | 0.671 |
PKG1 |
0.706 | -0.005 | -2 | 0.635 |
YANK2 |
0.705 | -0.054 | 2 | 0.474 |
CK1G1 |
0.703 | -0.037 | -3 | 0.582 |
CK1G3 |
0.684 | -0.048 | -3 | 0.382 |
CK1A |
0.666 | -0.045 | -3 | 0.429 |
CK1G2 |
0.663 | -0.059 | -3 | 0.489 |